Manjula Kurella Tamura

All Publications

• Effect of Starting Dialysis Versus Continuing Medical Management on Survival and Home Time in Older Adults With Kidney Failure : A Target Trial Emulation Study. Annals of internal medicine Montez-Rath, M. E., Thomas, I. C., Charu, V., Odden, M. C., Seib, C. D., Arya, S., Fung, E., O'Hare, A. M., Wong, S. P., Kurella Tamura, M. 2024

  Abstract

  For older adults with kidney failure who are not referred for transplant, medical management is an alternative to dialysis.To compare survival and home time between older adults who started dialysis at an estimated glomerular filtration rate (eGFR) less than 12 mL/min/1.73 m2 and those who continued medical management.Observational cohort study using target trial emulation.U.S. Department of Veterans Affairs, 2010 to 2018.Adults aged 65 years or older with chronic kidney failure and eGFR below 12 mL/min/1.73 m2 who were not referred for transplant.Starting dialysis within 30 days versus continuing medical management.Mean survival and number of days at home.Among 20 440 adults (mean age, 77.9 years [SD, 8.8]), the median time to dialysis start was 8.0 days in the group starting dialysis and 3.0 years in the group continuing medical management. Over a 3-year horizon, the group starting dialysis survived 770 days and the group continuing medical management survived 761 days (difference, 9.3 days [95% CI, -17.4 to 30.1 days]). Compared with the group continuing medical management, the group starting dialysis had 13.6 fewer days at home (CI, 7.7 to 20.5 fewer days at home). Compared with the group continuing medical management and forgoing dialysis completely, the group starting dialysis had longer survival by 77.6 days (CI, 62.8 to 91.1 days) and 14.7 fewer days at home (CI, 11.2 to 16.5 fewer days at home).Potential for unmeasured confounding due to lack of symptom assessments at eligibility; limited generalizability to women and nonveterans.Older adults starting dialysis when their eGFR fell below 12 mL/min/1.73 m2 who were not referred for transplant had modest gains in life expectancy and less time at home.U.S. Department of Veterans Affairs and National Institutes of Health.

  View details for DOI 10.7326/M23-3028

  View details for PubMedID 39159459

• Estimated Effect of Parathyroidectomy on Long-Term Kidney Function in Adults With Primary Hyperparathyroidism ANNALS OF INTERNAL MEDICINE Seib, C. D., Ganesan, C., Tamura, M. 2023; 176 (11): eL230279

  View details for DOI 10.7326/L23-0279

  View details for Web of Science ID 001155935800007

  View details for PubMedID 37983793

• Conservative Care for Kidney Failure-The Other Side of the Coin. JAMA network open Liu, C. K., Kurella Tamura, M. 2022; 5 (3): e222252

  View details for DOI 10.1001/jamanetworkopen.2022.2252

  View details for PubMedID 35285925

• National Estimates of CKD Prevalence and Potential Impact of Estimating Glomerular Filtration Rate Without Race. Journal of the American Society of Nephrology : JASN Duggal, V., Thomas, I., Montez-Rath, M. E., Chertow, G. M., Kurella Tamura, M. 2021

  Abstract

  BACKGROUND: The implications of removing the adjustment for Black race in equations to eGFR on the prevalence of CKD and management strategies are incompletely understood.METHODS: We estimated changes in CKD prevalence and the potential effect on therapeutic drug prescriptions and prediction of kidney failure if race adjustment were removed from the CKD-EPI GFR estimating equation. We used cross-sectional and longitudinal data from adults aged ≥18 years in the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2016, and the Veterans Affairs (VA) Health Care System in 2015. In the VA cohort, we assessed use of common medications that require dose adjustment on the basis of kidney function, and compared the prognostic accuracy of the Kidney Failure Risk Equation with versus without race adjustment of eGFR.RESULTS: The prevalence of CKD among Black adults increased from 5.2% to 10.6% in NHANES, and from 12.4% to 21.6% in the VA cohort after eliminating race adjustment. Among Black veterans, 41.0% of gabapentin users, 33.5% of ciprofloxacin users, 24.0% of metformin users, 6.9% of atenolol users, 6.6% of rosuvastatin users, and 5.8% of tramadol users were reclassified to a lower eGFR for which dose adjustment or discontinuation is recommended. Without race adjustment of eGFR, discrimination of the Kidney Failure Risk Equation among Black adults remained high and calibration was marginally improved overall, with better calibration at higher levels of predicted risk.CONCLUSIONS: Removal of race adjustment from CKD-EPI eGFR would double the estimated prevalence of CKD among Black adults in the United States. Such a change is likely to affect a sizeable number of drug-dosing decisions. It may also improve the accuracy of kidney failure risk prediction among higher-risk Black adults.

  View details for DOI 10.1681/ASN.2020121780

  View details for PubMedID 33958490

• Facility-Level Variation in Dialysis Use and Mortality Among Older Veterans With Incident Kidney Failure. JAMA network open Bradshaw, C. n., Thomas, I. C., Montez-Rath, M. E., Lorenz, K. A., Asch, S. M., Leppert, J. T., Wang, V. n., O'Hare, A. M., Kurella Tamura, M. n. 2021; 4 (1): e2034084

  Abstract

  Current guidelines lack consensus regarding the treatment of patients who may not benefit from dialysis; this lack of consensus may be associated with the substantial variation in dialysis use and outcomes across health care facilities.To assess the degree to which variation in dialysis use and mortality was associated with patient rather than facility characteristics and to distinguish which features identified the US Department of Veterans Affairs (VA) facilities with high rates of dialysis use.This cohort study analyzed data of veterans with stage 3 or 4 chronic kidney disease that progressed to kidney failure between January 1, 2011, and December 31, 2014. These patients received care from VA facilities across the US. Data sources included laboratory and administrative records from the VA, Medicare, and United States Renal Data System. Data analysis was conducted from August 1, 2019, to September 1, 2020.The primary exposure was the VA facility in which patients received most of their care before the onset of incident kidney failure defined as the first occurrence of either a sustained estimated glomerular filtration rate of less than 15 mL/min/1.73 m2 or the initiation of maintenance dialysis.The primary outcomes were dialysis use and mortality within 2 years of incident kidney failure. Median rate ratio was used to quantify facility-level variation, and variance partition coefficient was used to quantify the sources of unexplained variation.The cohort included 8695 older veterans with a mean (SD) age of 78.8 (7.5) years who were predominantly male (8573 [99%]) and White (6102 [70%]) individuals treated at 108 VA facilities. The observed frequency of dialysis use across facilities ranged from 25.0% to 81.4%, with a median (interquartile range [IQR]) rate of 51.7% (48.4%-60.0%). The observed frequency of mortality across facilities ranged from 27.2% to 60.0%, with a median (IQR) rate of 45.2% (41.2%-48.6%). The median rate ratio (adjusted for multiple patient and facility characteristics) was 1.40 for dialysis use and 1.08 for mortality. The unexplained variation in both outcomes mainly derived from patient characteristics rather than facility characteristics. No correlation was found between dialysis use and mortality at the facility level (correlation coefficient = 0.03).This study found sizable variation in dialysis use for older adults that was poorly correlated with facility-level mortality rates and was not accounted for by differences in measured patient and facility characteristics. These findings suggest opportunities to improve the degree to which dialysis use practices align with the values, goals, and preferences of older adults with kidney failure.

  View details for DOI 10.1001/jamanetworkopen.2020.34084

  View details for PubMedID 33449098

• Kidney Disease, Intensive Hypertension Treatment, and Risk for Dementia and Mild Cognitive Impairment: The Systolic Blood Pressure Intervention Trial JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kurella Tamura, M., Gaussoin, S. A., Pajewski, N. M., Chelune, G. J., Freedman, B. I., Gure, T. R., Haley, W. E., Killeen, A. A., Oparil, S., Rapp, S. R., Rifkin, D. E., Supiano, M., Williamson, J. D., Weiner, D. E. 2020; 31 (9): 2122-2132

  Abstract

  Intensively treating hypertension may benefit cardiovascular disease and cognitive function, but at the short-term expense of reduced kidney function.We investigated markers of kidney function and the effect of intensive hypertension treatment on incidence of dementia and mild cognitive impairment (MCI) in 9361 participants in the randomized Systolic Blood Pressure Intervention Trial, which compared intensive versus standard systolic BP lowering (targeting <120 mm Hg versus <140 mm Hg, respectively). We categorized participants according to baseline and longitudinal changes in eGFR and urinary albumin-to-creatinine ratio. Primary outcomes were occurrence of adjudicated probable dementia and MCI.Among 8563 participants who completed at least one cognitive assessment during follow-up (median 5.1 years), probable dementia occurred in 325 (3.8%) and MCI in 640 (7.6%) participants. In multivariable adjusted analyses, there was no significant association between baseline eGFR <60 ml/min per 1.73 m2 and risk for dementia or MCI. In time-varying analyses, eGFR decline ≥30% was associated with a higher risk for probable dementia. Incident eGFR <60 ml/min per 1.73 m2 was associated with a higher risk for MCI and a composite of dementia or MCI. Although these kidney events occurred more frequently in the intensive treatment group, there was no evidence that they modified or attenuated the effect of intensive treatment on dementia and MCI incidence. Baseline and incident urinary ACR ≥30 mg/g were not associated with probable dementia or MCI, nor did the urinary ACR modify the effect of intensive treatment on cognitive outcomes.Among hypertensive adults, declining kidney function measured by eGFR is associated with increased risk for probable dementia and MCI, independent of the intensity of hypertension treatment.

  View details for DOI 10.1681/ASN.2020010038

  View details for Web of Science ID 000571810200015

  View details for PubMedID 32591439

  View details for PubMedCentralID PMC7461687

• Dialysis Initiation and Mortality Among Older Veterans With Kidney Failure Treated in Medicare vs the Department of Veterans Affairs JAMA INTERNAL MEDICINE Tamura, M., Thomas, I., Montez-Rath, M. E., Kapphahn, K., Desai, M., Gale, R. C., Asch, S. M. 2018; 178 (5): 657–64

  Abstract

  The benefits of maintenance dialysis for older adults with end-stage renal disease (ESRD) are uncertain. Whether the setting of pre-ESRD nephrology care influences initiation of dialysis and mortality is not known.To compare initiation of dialysis and mortality among older veterans with incident kidney failure who received pre-ESRD nephrology care in fee-for-service Medicare vs the Department of Veterans Affairs (VA).Retrospective cohort study of patients from the US Medicare and VA health care systems evaluated 11 215 veterans aged 67 years or older with incident kidney failure between January 1, 2008, and December 31, 2011. Data analysis was performed March 15, 2016, through September 20, 2017.Pre-ESRD nephrology care in Medicare vs VA health care systems.Dialysis treatment and death within 2 years.Of the 11 215 patients included in the study, 11 085 (98.8%) were men; mean (SD) age was 79.1 (6.9) years. Within 2 years of incident kidney failure, 7071 (63.0%) of the patients started dialysis and 5280 (47.1%) died. Patients who received pre-ESRD nephrology care in Medicare were more likely to undergo dialysis compared with patients who received pre-ESRD nephrology care in VA (82% vs 53%; adjusted risk difference, 28 percentage points; 95% CI, 26-30 percentage points). Differences in dialysis initiation between Medicare and VA were more pronounced among patients aged 80 years or older and patients with dementia or metastatic cancer, and less pronounced among patients with paralysis (P < .05 for interaction). Two-year mortality was higher for patients who received pre-ESRD care in Medicare compared with VA (53% vs 44%; adjusted risk difference, 5 percentage points; 95% CI, 3-7 percentage points). The findings were similar in a propensity-matched analysis.Veterans who receive pre-ESRD nephrology care in Medicare receive dialysis more often yet are also more likely to die within 2 years compared with those in VA. The VA's integrated health care system and financing appear to favor lower-intensity treatment for kidney failure in older patients without a concomitant increase in mortality.

  View details for PubMedID 29630695

• Optimizing renal replacement therapy in older adults: a framework for making individualized decisions KIDNEY INTERNATIONAL Tamura, M. K., Tan, J. C., O'Hare, A. M. 2012; 82 (3): 261-269

  Abstract

  It is often difficult to synthesize information about the risks and benefits of recommended management strategies in older patients with end-stage renal disease since they may have more comorbidity and lower life expectancy than patients described in clinical trials or practice guidelines. In this review, we outline a framework for individualizing end-stage renal disease management decisions in older patients. The framework considers three factors: life expectancy, the risks and benefits of competing treatment strategies, and patient preferences. We illustrate the use of this framework by applying it to three key end-stage renal disease decisions in older patients with varying life expectancy: choice of dialysis modality, choice of vascular access for hemodialysis, and referral for kidney transplantation. In several instances, this approach might provide support for treatment decisions that directly contradict available practice guidelines, illustrating circumstances when strict application of guidelines may be inappropriate for certain patients. By combining quantitative estimates of benefits and harms with qualitative assessments of patient preferences, clinicians may be better able to tailor treatment recommendations to individual older patients, thereby improving the overall quality of end-stage renal disease care.

  View details for DOI 10.1038/ki.2011.384

  View details for Web of Science ID 000306370500005

  View details for PubMedID 22089945

  View details for PubMedCentralID PMC3396777

• Regional Variation in Health Care Intensity and Treatment Practices for End-stage Renal Disease in Older Adults JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION O'Hare, A. M., Rodriguez, R. A., Hailpern, S. M., Larson, E. B., Tamura, M. K. 2010; 304 (2): 180-186

  Abstract

  An increasing number of older adults are being treated for end-stage renal disease (ESRD) with long-term dialysis.To determine how ESRD treatment practices for older adults vary across regions with differing end-of-life intensity of care.Retrospective observational study using a national ESRD registry to identify a cohort of 41,420 adults (of white or black race), aged 65 years or older, who started long-term dialysis or received a kidney transplant between June 1, 2005, and May 31, 2006. Regional end-of-life intensity of care was defined using an index from the Dartmouth Atlas of Healthcare.Incidence of treated ESRD (dialysis or transplant), preparedness for ESRD (under the care of a nephrologist, having a fistula [vs graft or catheter] at time of hemodialysis initiation), and end-of-life care practices.Among whites, the incidence of ESRD was progressively higher in regions with greater intensity of care and this trend was most pronounced at older ages. Among blacks, a similar relationship was present only at advanced ages (men aged > or = 80 years and women aged > or = 85 years). Patients living in regions in the highest compared with lowest quintile of end-of-life intensity of care were less likely to be under the care of a nephrologist before the onset of ESRD (62.3% [95% confidence interval {CI}, 61.3%-63.3%] vs 71.1% [95% CI, 69.9%-72.2%], respectively) and less likely to have a fistula (vs graft or catheter) at the time of hemodialysis initiation (11.2% [95% CI, 10.6%-11.8%] vs 16.9% [95% CI, 15.9%-17.8%]). Among patients who died within 2 years of ESRD onset (n = 21,190), those living in regions in the highest compared with lowest quintile of end-of-life intensity of care were less likely to have discontinued dialysis before death (22.2% [95% CI, 21.1%-23.4%] vs 44.3% [95% CI, 42.5%-46.1%], respectively), less likely to have received hospice care (20.7% [95% CI, 19.5%-21.9%] vs 33.5% [95% CI, 31.7%-35.4%]), and more likely to have died in the hospital (67.8% [95% CI, 66.5%-69.1%] vs 50.3% [95% CI, 48.5%-52.1%]). These differences persisted in adjusted analyses.There are pronounced regional differences in treatment practices for ESRD in older adults that are not explained by differences in patient characteristics.

  View details for Web of Science ID 000279811000024

  View details for PubMedID 20628131

  View details for PubMedCentralID PMC3477643

• Functional Status of Elderly Adults before and after Initiation of Dialysis NEW ENGLAND JOURNAL OF MEDICINE Tamura, M. K., Covinsky, K. E., Chertow, G. M., Yaffe, K., Landefeld, C. S., McCulloch, C. E. 2009; 361 (16): 1539-1547

  Abstract

  It is unclear whether functional status before dialysis is maintained after the initiation of this therapy in elderly patients with end-stage renal disease (ESRD).Using a national registry of patients undergoing dialysis, which was linked to a national registry of nursing home residents, we identified all 3702 nursing home residents in the United States who were starting treatment with dialysis between June 1998 and October 2000 and for whom at least one measurement of functional status was available before the initiation of dialysis. Functional status was measured by assessing the degree of dependence in seven activities of daily living (on the Minimum Data Set-Activities of Daily Living [MDS-ADL] scale of 0 to 28 points, with higher scores indicating greater functional difficulty).The median MDS-ADL score increased from 12 during the 3 months before the initiation of dialysis to 16 during the 3 months after the initiation of dialysis. Three months after the initiation of dialysis, functional status had been maintained in 39% of nursing home residents, but by 12 months after the initiation of dialysis, 58% had died and predialysis functional status had been maintained in only 13%. In a random-effects model, the initiation of dialysis was associated with a sharp decline in functional status, indicated by an increase of 2.8 points in the MDS-ADL score (95% confidence interval [CI], 2.5 to 3.0); this decline was independent of age, sex, race, and functional-status trajectory before the initiation of dialysis. The decline in functional status associated with the initiation of dialysis remained substantial (1.7 points; 95% CI, 1.4 to 2.1), even after adjustment for the presence or absence of an accelerated functional decline during the 3-month period before the initiation of dialysis.Among nursing home residents with ESRD, the initiation of dialysis is associated with a substantial and sustained decline in functional status.

  View details for PubMedID 19828531

• Octogenarians and nonagenarians starting dialysis in the United States ANNALS OF INTERNAL MEDICINE Kurella, M., Covinsky, K. E., Collins, A. J., Chertow, G. M. 2007; 146 (3): 177-183

  Abstract

  The elderly constitute the fastest-growing segment of the end-stage renal disease (ESRD) population, but the epidemiology and outcomes of dialysis among the very elderly, that is, those 80 years of age and older, have not been previously examined at a national level.To describe recent trends in the incidence and outcomes of octogenarians and nonagenarians starting dialysis.Observational study.U.S. Renal Data System, a comprehensive, national registry of patients with ESRD.Octogenarians and nonagenarians initiating dialysis between 1996 and 2003.Rates of dialysis initiation and survival.The number of octogenarians and nonagenarians starting dialysis increased from 7054 persons in 1996 to 13,577 persons in 2003, corresponding to an average annual increase in dialysis initiation of 9.8%. After we accounted for population growth, the rate of dialysis initiation increased by 57% (rate ratio, 1.57 [95% CI, 1.53 to 1.62]) between 1996 and 2003. One-year mortality for octogenarians and nonagenarians after dialysis initiation was 46%. Compared with octogenarians and nonagenarians initiating dialysis in 1996, those starting dialysis in 2003 had a higher glomerular filtration rate and less morbidity related to chronic kidney disease but no difference in 1-year survival. Clinical characteristics strongly associated with death were older age, nonambulatory status, and more comorbid conditions.Survival of patients with incident ESRD who did not begin dialysis could not be assessed.The number of octogenarians and nonagenarians initiating dialysis has increased considerably over the past decade, while overall survival for patients on dialysis remains modest. Estimates of prognosis based on patient characteristics, when considered in conjunction with individual values and preferences, may aid in dialysis decision making for the very elderly.

  View details for Web of Science ID 000243957400003

  View details for PubMedID 17283348

• Curcumin Supplementation and Vascular and Cognitive Function in Chronic Kidney Disease: A Randomized Controlled Trial. Antioxidants (Basel, Switzerland) Gimblet, C. J., Kruse, N. T., Geasland, K., Michelson, J., Sun, M., Ten Eyck, P., Linkenmeyer, C., Mandukhail, S. R., Rossman, M. J., Sambharia, M., Chonchol, M., Kurella Tamura, M., Seals, D., Hoth, K. F., Jalal, D. 2024; 13 (8)

  Abstract

  Chronic kidney disease (CKD) increases the risk of cardiovascular disease and cognitive impairment. Curcumin is a polyphenol that improves vascular and cognitive function in older adults; however, its effects on vascular and cognitive function in patients with CKD are unknown. We hypothesized that curcumin supplementation would improve vascular and cognitive function in patients with CKD. Eighty-eight adults diagnosed with stage 3b or 4 CKD (aged 66 ± 8 years, 75% male) participated in a 12-month, randomized, double-blind, placebo-controlled study to test the effects of curcumin (Longvida®, 2000 mg/day) on vascular and cognitive function. Our primary outcome was brachial artery flow-mediated dilation (FMD). Our secondary outcomes were nitroglycerin-mediated dilation, carotid-femoral pulse wave velocity (cfPWV), and cognitive function assessed via the NIH Toolbox Cognition Battery. At baseline, the mean estimated glomerular filtration rate was 34.7 ± 10.8, and the median albumin/creatinine ratio was 81.9 (9.7, 417.3). A total of 44% of participants had diabetes. Compared with placebo, 12 months of curcumin did not improve FMD (median change from baseline was -0.7 (-2.1, 1.1) and -0.1 (-1.5, 1.5) for curcumin and placebo, respectively, with p = 0.69). Similarly, there were no changes in nitroglycerin-mediated dilation, cfPWV, or cognitive outcomes. These results do not support chronic curcumin supplementation to improve vascular and cognitive function in patients with CKD.

  View details for DOI 10.3390/antiox13080983

  View details for PubMedID 39199229

  View details for PubMedCentralID PMC11352164

• Physical function and mortality in older adults with chronic kidney disease. Clinical journal of the American Society of Nephrology : CJASN Liu, C. K., Parvathinathan, G., Stedman, M. R., Seliger, S. L., Weiner, D. E., Tamura, M. K. 2024

  Abstract

  Accurate mortality prediction can guide clinical care for older adults with chronic kidney disease (CKD). Yet existing tools do not incorporate physical function, an independent predictor of death in older adults. We determined whether incorporating physical function measurements improve mortality prediction among older adults with CKD.We included Chronic Renal Insufficiency Cohort participants who were ≥65 years old, had estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73m2, not receiving kidney failure replacement therapy (KFRT), and had least one gait speed assessment. Gait speed was measured at usual pace (≥0.84, 0.83-0.65, 0.64-0.47, ≤0.46 meters/second, or unable), and frailty was assessed using Physical Frailty Phenotype criteria (range 0 to 5 points, also known as Fried criteria). We modeled time to all-cause death over five years using Cox proportional hazard models, treating KFRT as censored and non-censored events in separate analyses. C-statistics assessed model discrimination.Among 2,338 persons, mean age was 70±4 years; 43% were female and 43% were Black. Mean eGFR was 42±13 mL/min/1.73m2 and median urine albumin-to-creatinine ratio was 33 mg/g [Q1 9, Q3 206]. Over a median follow-period of 5 years, 392 died and 164 developed KFRT. In censored analyses, adding gait speed or frailty improved mortality risk prediction. The C-statistic changed from 0.69 to 0.72 with gait speed scores, and from 0.70 to 0.73 with frailty scores. The performance of models with gait speed or frailty was similar in non-censored analyses.Among older adults with CKD, adding measures of physical function modestly improves mortality prediction.

  View details for DOI 10.2215/CJN.0000000000000515

  View details for PubMedID 39115956

• Clonal hematopoiesis of indeterminate potential is associated with reduced risk of cognitive impairment in patients with chronic kidney disease. Alzheimer's & dementia : the journal of the Alzheimer's Association Xiao, C., Tamura, M. K., Pan, Y., Rao, V., Missikpode, C., Vlasschaert, C., Nakao, T., Sun, X., Li, C., Huang, Z., Anderson, A., Uddin, M. M., Kim, D. K., Taliercio, J., Deo, R., Bhat, Z., Xie, D., Rao, P., Chen, J., Lash, J. P., He, J., Natarajan, P., Hixson, J. E., Yaffe, K., Kelly, T. N. 2024

  Abstract

  Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean.Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted hazard ratio [HR] [95% confidence interval {CI}] = 0.44 [0.26, 0.76], p = 0.003) and executive function (adjusted HR [95% CI] = 0.60 [0.37, 0.97], p = 0.04). There were no significant associations between CHIP and impairment in global cognition or verbal memory.CHIP was associated with lower risks of impairment in attention and executive function among CKD patients.Our study is the first to examine the role of CHIP in cognitive decline in CKD. CHIP markedly decreased the risk of impairment in attention and executive function. CHIP was not associated with impairment in global cognition or verbal memory.

  View details for DOI 10.1002/alz.14182

  View details for PubMedID 39115897

• The Legacy Effect of Intensive versus Standard Blood Pressure Control on the Incidence of Dialysis or Kidney Transplantation. Journal of the American Society of Nephrology : JASN Pajewski, N. M., Beddhu, S., Bress, A. P., Chang, T. I., Chertow, G. M., Cheung, A. K., Cushman, W. C., Freedman, B. I., Greene, T., Johnson, K. C., Jaeger, B. C., Tamura, M. K., Lewis, C. E., Rahman, M., Reboussin, D. M., Rocco, M. V., Williamson, J. D., Whelton, P. K., Wright, J. T., Drawz, P. E., Ix, J. H. 2024

  Abstract

  The Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive lowering of systolic blood pressure (BP) increased the risk of incident chronic kidney disease and episodes of acute kidney injury. Whether intensive treatment changes the risk of kidney failure is unknown. The goal of this study was to estimate the legacy effect of intensive versus standard systolic BP lowering on the longer-term incidence of kidney failure.Secondary analysis of a randomized, open-label clinical trial with observational follow-up. Between 2010 and 2013, patients 50 years and older with hypertension and higher cardiovascular risk excluding those with diabetes mellitus, history of stroke, proteinuria >1g / day or polycystic kidney disease were recruited from 102 clinic sites in the United States and Puerto Rico. Participants were randomized to a systolic BP goal of <120 mm Hg (intensive treatment) or <140 mm Hg (standard treatment group). We linked participants with the US Renal Data System to ascertain kidney failure (initiation of dialysis therapy or transplantation) and the US National Death Index to ascertain all-cause mortality through 2020.Based on analysis of 9279 (99.1%) of 9361 randomized participants, 101 cases of kidney failure occurred over a median follow-up of 8.6 years (interquartile range 8.0 to 9.1 years), with the majority occurring in 74 (73.3%) participants with an eGFR<45 ml/min/1.73 m2 at baseline. Intensive treatment did not significantly increase the risk of kidney failure either overall (cause-specific Hazard Ratio (HR) = 1.20, 95% CI: 0.81 - 1.78) or in the subgroup of participants with baseline eGFR<45 ml/min/1.73 m2 (HR = 1.43, 95% CI: 0.89 - 2.30).Overall, and in patients with eGFR <45 ml/min/1.73 m2, there were higher rates of dialysis or transplantation among SPRINT participants randomized to intensive treatment, but the modest differences observed were not statistically significant.

  View details for DOI 10.1681/ASN.0000000000000459

  View details for PubMedID 39078712

• Representation of Real-World Adults With Chronic Kidney Disease in Clinical Trials Supporting Blood Pressure Treatment Targets. Journal of the American Heart Association Li, J., An, J., Huang, M., Zhou, M., Montez-Rath, M. E., Niu, F., Sim, J. J., Pao, A. C., Charu, V., Odden, M. C., Kurella Tamura, M. 2024: e031742

  Abstract

  Little is known about how well trial participants with chronic kidney disease (CKD) represent real-world adults with CKD. We assessed the population representativeness of clinical trials supporting the 2021 Kidney Disease: Improving Global Outcomes blood pressure (BP) guidelines in real-world adults with CKD.Using a cross-sectional analysis, we identified patients with CKD who met the guideline definition of hypertension based on use of antihypertensive medications or sustained systolic BP ≥120 mm Hg in 2019 in the Veterans Affairs and Kaiser Permanente of Southern California. We applied the eligibility criteria from 3 BP target trials, SPRINT (Systolic Pressure Intervention Trial), ACCORD (Action to Control Cardiovascular Risk in Diabetes), and AASK (African American Study of Kidney Disease), to estimate the proportion of adults with a systolic BP above the guideline-recommended target and the proportion who met eligibility criteria for ≥1 trial. We identified 503 480 adults in the Veterans Affairs and 73 412 adults in Kaiser Permanente of Southern California with CKD and hypertension in 2019. We estimated 79.7% in the Veterans Affairs and 87.3% in the Kaiser Permanente of Southern California populations had a systolic BP ≥120 mm Hg; only 23.8% [23.7%-24.0%] in the Veterans Affairs and 20.8% [20.5%-21.1%] in Kaiser Permanente of Southern California were trial-eligible. Among trial-ineligible patients, >50% met >1 exclusion criteria.Major BP target trials were representative of fewer than 1 in 4 real-world adults with CKD and hypertension. A large proportion of adults who are at risk for cardiovascular morbidity from hypertension and susceptible to adverse treatment effects lack relevant treatment information.

  View details for DOI 10.1161/JAHA.123.031742

  View details for PubMedID 38533947

• Building the Evidence for Advance Care Planning for Patients Receiving Dialysis. JAMA network open Kurella Tamura, M., Holdsworth, L. M. 2024; 7 (1): e2352415

  View details for DOI 10.1001/jamanetworkopen.2023.52415

  View details for PubMedID 38289607

• "Diving in the deep-end and swimming": a mixed methods study using normalization process theory to evaluate a learning collaborative approach for the implementation of palliative care practices in hemodialysis centers. BMC health services research Holdsworth, L. M., Stedman, M., Gustafsson, E. S., Han, J., Asch, S. M., Harbert, G., Lorenz, K. A., Lupu, D. E., Malcolm, E., Moss, A. H., Nicklas, A., Tamura, M. K. 2023; 23 (1): 1384

  Abstract

  Normalization Process Theory (NPT) is an implementation theory that can be used to explain how and why implementation strategies work or not in particular circumstances. We used it to understand the mechanisms that lead to the adoption and routinization of palliative care within hemodialysis centers.We employed a longitudinal, mixed methods approach to comprehensively evaluate the implementation of palliative care practices among ten hemodialysis centers participating in an Institute for Healthcare Improvement Breakthrough- Series learning collaborative. Qualitative methods included longitudinal observations of collaborative activities, and interviews with implementers at the end of the study. We used an inductive and deductive approach to thematic analysis informed by NPT constructs (coherence, cognitive participation, collective action, reflexive monitoring) and implementation outcomes. The NoMAD survey, which measures NPT constructs, was completed by implementers at each hemodialysis center during early and late implementation.The four mechanisms posited in NPT had a dynamic and layered relationship during the implementation process. Collaborative participants participated because they believed in the value and legitimacy of palliative care for patients receiving hemodialysis and thus had high levels of cognitive participation at the start. Didactic Learning Sessions were important for building practice coherence, and sense-making was solidified through testing new skills in practice and first-hand observation during coaching visits by an expert. Collective action was hampered by limited time among team members and practical issues such as arranging meetings with patients. Reflexive monitoring of the positive benefit to patient and family experiences was key in shifting mindsets from disease-centric towards a patient-centered model of care. NoMAD survey scores showed modest improvement over time, with collective action having the lowest scores.NPT was a useful framework for understanding the implementation of palliative care practices within hemodialysis centers. We found a nonlinear relationship among the mechanisms which is reflected in our model of implementation of palliative care practices through a learning collaborative. These findings suggest that the implementation of complex practices such as palliative care may be more successful through iterative learning and practice opportunities as the mechanisms for change are layered and mutually reinforcing.ClinicalTrials.gov, NCT04125537 . Registered 14 October 2019 - Retrospectively registered.

  View details for DOI 10.1186/s12913-023-10360-7

  View details for PubMedID 38082293

  View details for PubMedCentralID PMC10712060

• Heterogeneous Treatment Effects of Intensive Glycemic Control on Kidney Microvascular Outcomes and Mortality in ACCORD. Journal of the American Society of Nephrology : JASN Charu, V., Liang, J. W., Chertow, G. M., Li, J., Montez-Rath, M. E., Geldsetzer, P., de Boer, I. H., Tian, L., Tamura, M. K. 2023

  Abstract

  Clear criteria to individualize glycemic targets in patients with type II diabetes are lacking. In this post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes trial (ACCORD), we evaluate whether the kidney failure risk equation (KFRE) can identify patients for whom intensive glycemic control confers more benefit in preventing kidney microvascular outcomes.We divided the ACCORD trial population into quartiles based on 5-year kidney failure risk using the KFRE. We estimated conditional treatment effects within each quartile and compared them to the average treatment effect in the trial. The treatment effects of interest were the 7-year restricted-mean-survival-time (RMST) differences between intensive and standard glycemic control arms on (1) time-to-first development of severely elevated albuminuria or kidney failure and (2) all-cause mortality.We found evidence that the effect of intensive glycemic control on kidney microvascular outcomes and all-cause mortality varies with baseline risk of kidney failure. Patients with elevated baseline risk of kidney failure derived the most from intensive glycemic control in reducing kidney microvascular outcomes (7-year RMST difference of 114.8 (95% CI 58.1, 176.4)v. 48.4 (25.3, 69.6) days in the entire trial population) However, this same patient group also experienced a shorter time to death (7-year RMST difference of -56.7 (-100.2, -17.5) v. -23.6 (-42.2, -6.6)days).We found evidence of heterogenous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD as a function of predicted baseline risk of kidney failure. Patients with higher kidney failure risk experienced the most pronounced reduction in kidney microvascular outcomes but also experienced the highest risk of all-cause mortality.

  View details for DOI 10.1681/ASN.0000000000000272

  View details for PubMedID 38073026

• Estimated Effect of Parathyroidectomy on Long-Term Kidney Function in Adults With Primary Hyperparathyroidism. Annals of internal medicine Seib, C. D., Ganesan, C., Tamura, M. K. 2023; 176 (11): eL230280

  View details for DOI 10.7326/L23-0280

  View details for PubMedID 37983791

• Treatment and Control of Hypertension Among Adults With Chronic Kidney Disease, 2011 to 2019. Hypertension (Dallas, Tex. : 1979) Martinez, J. D., Thomas, I. C., Montez-Rath, M. E., Pao, A. C., Fung, E., Charu, V., Sim, J. J., An, J., Odden, M. C., Kurella Tamura, M. 2023

  Abstract

  Hypertension frequently accompanies chronic kidney disease (CKD) as etiology and sequela. We examined contemporary trends in hypertension treatment and control in a national sample of adults with CKD.We evaluated 5% cross-sectional samples of adults with CKD between 2011 and 2019 in the Veterans Health Administration. We defined CKD as a sustained estimated glomerular filtration rate value <60 mL/min per 1.73 m2 or a urine albumin-to-creatinine ratio ≥30 mg/g. The main outcomes were blood pressure (BP) control, defined as a systolic BP <140 mm Hg and a diastolic BP <90 mm Hg based on the mean of monthly BP measurements, and prescriptions for antihypertensive medications.The annual samples ranged between n=22 110 and n=33 039 individuals, with a mean age of 72 years, 96% of whom were male. Between 2011 and 2014, the age-adjusted proportion of adults with controlled BP declined from 78.0% to 72.2% (P value for linear trend, <0.001), reached a nadir of 71.0% in 2015, and then increased to 72.9% by 2019 (P value for linear trend, <0.001). Among adults with BP above goal, the age-adjusted proportion who did not receive antihypertensive treatment increased throughout the decade from 18.8% to 21.6%, and the age-adjusted proportion who received ≥3 antihypertensive medications decreased from 41.8% to 36.3%. Prescriptions for first-line antihypertensive agents also decreased.Among adults with CKD treated in the Veterans Health Administration, the proportion with controlled BP declined between 2011 and 2015 followed by a modest increase, coinciding with fewer prescriptions for antihypertensive medications.

  View details for DOI 10.1161/HYPERTENSIONAHA.123.21523

  View details for PubMedID 37706307

• Using Restricted Mean Survival Time to Improve Interpretability of Time-to-Event Data Analysis. Clinical journal of the American Society of Nephrology : CJASN Charu, V., Tian, L., Kurella-Tamura, M., Montez-Rath, M. E. 2023

  View details for DOI 10.2215/CJN.0000000000000323

  View details for PubMedID 37707829

• Using Relative Survival to Estimate the Burden of Kidney Failure. American journal of kidney diseases : the official journal of the National Kidney Foundation Stedman, M. R., Tamura, M. K., Chertow, G. M. 2023

  Abstract

  Estimates of mortality from kidney failure are misleading because the mortality from kidney failure is inseparable from the mortality attributed to comorbid conditions. We sought to develop an alternative method to reduce the bias in estimating mortality due to kidney failure using life table methods.Longitudinal cohort study.Using data from the United States Renal Data System and the Medicare 5% sample, we identified an incident cohort of patients, age 66+, who first had kidney failure in 2009 and a similar general population cohort without kidney failure.Kidney failure.Death.We created comorbidity, age, sex, race, and year-specific life tables to estimate relative survival of patients with incident kidney failure and to attain an estimate of excess kidney failure-related deaths. Estimates were compared with those based on standard life tables (not adjusted for comorbidity).The analysis included 31,944 adults with kidney failure with a mean age of 77 +/- 7 years. 5-year relative survival was 31% using standard life tables (adjusted for age, sex, race, and year) versus 36% using life tables also adjusted for comorbidities. Compared with other chronic diseases, patients with kidney failure have among the lowest relative survival. Patients with incident kidney failure ages 66-70 and 76-80 have a survival comparable to adults without kidney failure roughly 86-90 and 91-95 years old, respectively.Relative survival estimates can be improved by narrowing the specificity of the covariates collected, (e.g. disease severity and ethnicity).Estimates of survival relative to a matched general population partition the mortality due to kidney failure from other causes of death. Results highlight the immense burden of kidney failure on mortality and the importance of disease prevention efforts among older adults.

  View details for DOI 10.1053/j.ajkd.2023.05.015

  View details for PubMedID 37678740

• INAPPROPRIATE OPIOID PRESCRIBING AMONG VETERANS WITH KIDNEY DISEASE Ma, J., Garcia, A., Black, A. C., Giannitrapani, K., Boothroyd, D., Tamura, M. K., Thomas, I., Midboe, A., Troszak, L. K., Zhang, S., Bozkurt, S., Check, D., Merlin, J. S., Bowling, B., Becker, W., Karl, L. SPRINGER. 2023: S343

  View details for Web of Science ID 001043057201156

• Addressing Racial Injustice, Developing Cultural Humility, and Fostering Rapport-Building Communication Skills to Improve Disparities in End-of-Life Planning. Journal of pain and symptom management Saeed, F., Eneanya, A., Allen, R. J., Tamura, M. K., Fiscella, K. A. 2023

  View details for DOI 10.1016/j.jpainsymman.2023.05.019

  View details for PubMedID 37355055

• Heterogeneous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD. medRxiv : the preprint server for health sciences Charu, V., Liang, J. W., Chertow, G. M., Li, Z. J., Montez-Rath, M. E., Geldsetzer, P., de Boer, I. H., Tian, L., Tamura, M. K. 2023

  Abstract

  Objective: Clear criteria to individualize glycemic targets are lacking. In this post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes trial (ACCORD), we evaluate whether the kidney failure risk equation (KFRE) can identify patients who disproportionately benefit from intensive glycemic control on kidney microvascular outcomes.Research design and methods: We divided the ACCORD trial population in quartiles based on 5-year kidney failure risk using the KFRE. We estimated conditional treatment effects within each quartile and compared them to the average treatment effect in the trial. The treatment effects of interest were the 7-year restricted-mean-survival-time (RMST) differences between intensive and standard glycemic control arms on (1) time-to-first development of severely elevated albuminuria or kidney failure and (2) all-cause mortality.Results: We found evidence that the effect of intensive glycemic control on kidney microvascular outcomes and all-cause mortality varies with baseline risk of kidney failure. Patients with elevated baseline risk of kidney failure benefitted the most from intensive glycemic control on kidney microvascular outcomes (7-year RMST difference of 115 v. 48 days in the entire trial population) However, this same patient group also experienced shorter times to death (7-year RMST difference of -57 v. -24 days).Conclusions: We found evidence of heterogenous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD as a function of predicted baseline risk of kidney failure. Patients with higher kidney failure risk experienced the most pronounced benefits of treatment on kidney microvascular outcomes but also experienced the highest risk of all-cause mortality.

  View details for DOI 10.1101/2023.06.14.23291396

  View details for PubMedID 37398349

• Blood Pressure, Incident Cognitive Impairment, and Severity of CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. American journal of kidney diseases : the official journal of the National Kidney Foundation Babroudi, S., Tighiouart, H., Schrauben, S. J., Cohen, J. B., Fischer, M. J., Rahman, M., Hsu, C. Y., Sozio, S. M., Weir, M., Sarnak, M., Yaffe, K., Tamura, M. K., Drew, D. 2023

  Abstract

  Hypertension is a known risk factor for dementia and cognitive impairment. There are limited data on the relation of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with incident cognitive impairment in adults with chronic kidney disease. We sought to identify and characterize the relationship among blood pressure, cognitive impairment, and severity of decreased kidney function in adults with chronic kidney disease.Longitudinal Cohort study.3,768 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study.Baseline SBP and DBP were examined as exposure variables, using continuous (linear, per 10-mm Hg higher), categorical (SBP <120 (reference), 120 to 140, >140 mm Hg; DBP <70 (reference), 70 to 80, >80 mm Hg) and non-linear terms (splines).Incident cognitive impairment defined as a decline in modified mini-mental state exam (3MS) score to greater than 1 standard deviation (SD) below the cohort mean.Cox proportional hazard models adjusted for demographics as well as kidney disease and cardiovascular disease risk factors.The mean (SD) age of participants was 58 (11) years, eGFR was 44 mL/min/1.73m2 (15) and the median (IQR) follow-up time was 11 (7, 13) years. In 3,048 participants without cognitive impairment at baseline and with at least one follow-up 3MS test, higher baseline SBP was significantly associated with incident cognitive impairment only in the eGFR >45 mL/min/1.73m2 subgroup [adjusted hazard ratio (AHR) 1.13, 95% CI 1.05-1.22 per 10-mm Hg higher SBP]. Spline analyses, aimed at exploring non-linearity, showed that the relationship between baseline SBP and incident cognitive impairment was J-shaped and significant only in the eGFR >45 mL/min/1.73m2 subgroup (p=0.02). Baseline DBP was not associated with incident cognitive impairment in any analyses.3MS test as the primary measure of cognitive function.Among patients with chronic kidney disease, higher baseline SBP was associated with higher risk of incident cognitive impairment specifically in those individuals with eGFR >45 ml/min/1.73m2.

  View details for DOI 10.1053/j.ajkd.2023.03.012

  View details for PubMedID 37245689

• Intensive Blood Pressure Management Preserves Functional Connectivity in Patients with Hypertension from the Systolic Blood Pressure Intervention Randomized Trial. AJNR. American journal of neuroradiology Shah, C., Srinivasan, D., Erus, G., Kurella Tamura, M., Habes, M., Detre, J. A., Haley, W. E., Lerner, A. J., Wright, C. B., Wright, J. T., Oparil, S., Kritchevsky, S. B., Punzi, H. A., Rastogi, A., Malhotra, R., Still, C. H., Williamson, J. D., Bryan, R. N., Fan, Y., Nasrallah, I. M. 2023

  Abstract

  The Systolic Blood Pressure Intervention (SPRINT) randomized trial demonstrated that intensive blood pressure management resulted in slower progression of cerebral white matter hyperintensities, compared with standard therapy. We assessed longitudinal changes in brain functional connectivity to determine whether intensive treatment results in less decline in functional connectivity and how changes in brain functional connectivity relate to changes in brain structure.Five hundred forty-eight participants completed longitudinal brain MR imaging, including resting-state fMRI, during a median follow-up of 3.84 years. Functional brain networks were identified using independent component analysis, and a mean connectivity score was calculated for each network. Longitudinal changes in mean connectivity score were compared between treatment groups using a 2-sample t test, followed by a voxelwise t test. In the full cohort, adjusted linear regression analysis was performed between changes in the mean connectivity score and changes in structural MR imaging metrics.Four hundred six participants had longitudinal imaging that passed quality control. The auditory-salience-language network demonstrated a significantly larger decline in the mean connectivity score in the standard treatment group relative to the intensive treatment group (P = .014), with regions of significant difference between treatment groups in the cingulate and right temporal/insular regions. There was no treatment group difference in other networks. Longitudinal changes in mean connectivity score of the default mode network but not the auditory-salience-language network demonstrated a significant correlation with longitudinal changes in white matter hyperintensities (P = .013).Intensive treatment was associated with preservation of functional connectivity of the auditory-salience-language network, while mean network connectivity in other networks was not significantly different between intensive and standard therapy. A longitudinal increase in the white matter hyperintensity burden is associated with a decline in mean connectivity of the default mode network.

  View details for DOI 10.3174/ajnr.A7852

  View details for PubMedID 37105682

• Estimated Effect of Parathyroidectomy on Long-Term Kidney Function in Adults With Primary Hyperparathyroidism. Annals of internal medicine Seib, C. D., Ganesan, C., Furst, A., Pao, A. C., Chertow, G. M., Leppert, J. T., Suh, I., Montez-Rath, M. E., Harris, A. H., Trickey, A. W., Kebebew, E., Tamura, M. K. 2023

  Abstract

  BACKGROUND: Multidisciplinary guidelines recommend parathyroidectomy to slow the progression of chronic kidney disease in patients with primary hyperparathyroidism (PHPT) and an estimated glomerular filtration rate (eGFR) less than 60mL/min/1.73 m2. Limited data address the effect of parathyroidectomy on long-term kidney function.OBJECTIVE: To compare the incidence of a sustained decline in eGFR of at least 50% among patients with PHPT treated with parathyroidectomy versus nonoperative management.DESIGN: Target trial emulation was done using observational data from adults with PHPT, using an extended Cox model with time-varying inverse probability weighting.SETTING: Veterans Health Administration.PATIENTS: Patients with a new biochemical diagnosis of PHPT in 2000 to 2019.MEASUREMENTS: Sustained decline of at least 50% from pretreatment eGFR.RESULTS: Among 43697 patients with PHPT (mean age, 66.8years), 2928 (6.7%) had a decline of at least 50% in eGFR over a median follow-up of 4.9years. The weighted cumulative incidence of eGFR decline was 5.1% at 5years and 10.8% at 10 years in patients managed with parathyroidectomy, compared with 5.1% and 12.0%, respectively, in those managed nonoperatively. The adjusted hazard of eGFR decline did not differ between parathyroidectomy and nonoperative management (hazard ratio [HR], 0.98 [95% CI, 0.82 to 1.16]). Subgroup analyses found no heterogeneity of treatment effect based on pretreatment kidney function. Parathyroidectomy was associated with a reduced hazard of the primary outcome among patients younger than 60years (HR, 0.75 [CI, 0.59 to 0.93]) that was not evident among those aged 60years or older (HR, 1.08 [CI, 0.87 to 1.34]).LIMITATION: Analyses were done in a predominantly male cohort using observational data.CONCLUSION: Parathyroidectomy had no effect on long-term kidney function in older adults with PHPT. Potential benefits related to kidney function should not be the primary consideration for PHPT treatment decisions.PRIMARY FUNDING SOURCE: National Institute on Aging.

  View details for DOI 10.7326/M22-2222

  View details for PubMedID 37037034

• Value Placed on Comfort vs Life Prolongation Among Patients Treated With Maintenance Dialysis. JAMA internal medicine Wong, S. P., Prince, D. K., Kurella Tamura, M., Hall, Y. N., Butler, C. R., Engelberg, R. A., Vig, E. K., Curtis, J. R., O'Hare, A. M. 2023

  Abstract

  Patients receiving maintenance dialysis experience intensive patterns of end-of-life care that might not be consistent with their values.To evaluate the association of patients' health care values with engagement in advance care planning and end-of-life care.Survey study of patients who received maintenance dialysis between 2015 and 2018 at dialysis centers in the greater metropolitan areas of Seattle, Washington, and Nashville, Tennessee, with longitudinal follow-up of decedents. Logistic regression models were used to estimate probabilities. Data analysis was conducted between May and October 2022.A survey question about the value that the participant would place on longevity-focused vs comfort-focused care if they were to become seriously ill.Self-reported engagement in advance care planning and care received near the end of life through 2020 using linked kidney registry data and Medicare claims.Of 933 patients (mean [SD] age, 62.6 [14.0] years; 525 male patients [56.3%]; 254 [27.2%] identified as Black) who responded to the question about values and could be linked to registry data (65.2% response rate [933 of 1431 eligible patients]), 452 (48.4%) indicated that they would value comfort-focused care, 179 (19.2%) that they would value longevity-focused care, and 302 (32.4%) that they were unsure about the intensity of care they would value. Many had not completed an advance directive (estimated probability, 47.5% [95% CI, 42.9%-52.1%] of those who would value comfort-focused care vs 28.1% [95% CI, 24.0%-32.3%] of those who would value longevity-focused care or were unsure; P < .001), had not discussed hospice (estimated probability, 28.6% [95% CI, 24.6%-32.9%] comfort focused vs 18.2% [95% CI, 14.7%-21.7%] longevity focused or unsure; P < .001), or had not discussed stopping dialysis (estimated probability, 33.3% [95% CI, 29.0%-37.7%] comfort focused vs 21.9% [95% CI, 18.2%-25.8%] longevity focused or unsure; P < .001). Most respondents wanted to receive cardiopulmonary resuscitation (estimated probability, 78.0% [95% CI, 74.2%-81.7%] comfort focused vs 93.9% [95% CI, 91.4%-96.1%] longevity focused or unsure; P < .001) and mechanical ventilation (estimated probability, 52.0% [95% CI, 47.4%-56.6%] comfort focused vs 77.9% [95% CI, 74.0%-81.7%] longevity focused or unsure; P < .001). Among decedents, the percentages of participants who received an intensive procedure during the final month of life (estimated probability, 23.5% [95% CI, 16.5%-31.0%] comfort focused vs 26.1% [95% CI, 18.0%-34.5%] longevity focused or unsure; P = .64), discontinued dialysis (estimated probability, 38.3% [95% CI, 32.0%-44.8%] comfort focused vs 30.2% [95% CI, 23.0%-37.8%] longevity focused or unsure; P = .09), and enrolled in hospice (estimated probability, 32.2% [95% CI, 25.7%-38.7%] comfort focused vs 23.3% [95% CI, 16.4%-30.5%] longevity focused or unsure; P = .07) were not statistically different.This survey study found that there appeared to be a disconnect between patients' expressed values, which were largely comfort focused, and their engagement in advance care planning and end-of-life care, which reflected a focus on longevity. These findings suggest important opportunities to improve the quality of care for patients receiving dialysis.

  View details for DOI 10.1001/jamainternmed.2023.0265

  View details for PubMedID 36972031

  View details for PubMedCentralID PMC10043804

• Racial Disparities in Health Beliefs and Advance Care Planning Among Patients Receiving Maintenance Dialysis. Journal of pain and symptom management Saeed, F., Ladwig, S., Allen, R. J., Eneanya, N. D., Tamura, M. K., Fiscella, K. A. 2022

  Abstract

  INTRODUCTION: Among people receiving maintenance dialysis, little is known about racial disparities in the occurrence of prognostic discussions, beliefs about future health, and completion of advance care planning (ACP) documents. We examined whether Black patients receiving maintenance dialysis differ from White patients in prognostic discussions, beliefs about future health, and completion of ACP-related documents.METHODS: We surveyed adult patients receiving maintenance dialysis from seven dialysis units in Cleveland, Ohio, and hospitalized patients at a tertiary care hospital in Cleveland. Of the 450 patients who were asked to participate in the study, 423 (94%) agreed. We restricted the current secondary analyses to include only Black (n=285) and White (n=114) patients. The survey assessed patients' knowledge of their kidney disease, attitudes toward chronic kidney disease (CKD) treatment, preferences for end-of-life (EoL) care, the patient-reported occurrence of prognostic discussions, experiences with kidney therapy decision making, sentiments of dialysis regret, beliefs about health over the next 12 months, and advance care planning. We used stepwise logistic regression to determine if race was associated with the occurrence of prognostic discussions, beliefs about future health, and completion of an ACP-related document, while controlling for potential confounders.RESULTS: We found no significant difference in the frequency of prognostic discussions between Black (11.9%) versus White patients (7%) (P=0.15). However, Black patients (19%) had lower odds of believing that their health would worsen over the next 12 months (OR 0.22, CI 0.12, 0.44) and reporting completion of any ACP-related document (OR 0.5, CI 0.32, 0.81) compared to White patients CONCLUSIONS: Racial differences exist in beliefs about future health and completion of ACP-related documents. Systemic efforts to investigate differences in health beliefs and address racial disparities in the completion of ACP-related documents are needed.

  View details for DOI 10.1016/j.jpainsymman.2022.12.002

  View details for PubMedID 36521766

• Risk of permanent hypoparathyroidism requiring calcitriol therapy in a population-based cohort of adults older than 65 undergoing total thyroidectomy for Graves' disease. Thyroid : official journal of the American Thyroid Association Seib, C. D., Meng, T., Cisco, R. M., Lin, D. T., McAninch, E. A., Chen, J., Tamura, M. K., Trickey, A. W., Kebebew, E. 2022

  Abstract

  Total thyroidectomy for Graves' disease (GD) is associated with rapid treatment of hyperthyroidism and low recurrence rates. However, it carries the risk of surgical complications including permanent hypoparathyroidism, which contribute to long-term impaired quality of life. The objective of this study was to determine the incidence of permanent hypoparathyroidism requiring calcitriol therapy among a population-based cohort of older adults undergoing total thyroidectomy for GD in the U.S.We performed a population-based cohort study using 100% Medicare claims from beneficiaries older than 65 with GD who underwent total thyroidectomy from 2007 to 2017. We required continuous enrollment in Medicare Parts A, B, and D for 12 months before and after surgery to ensure access to comprehensive claims data. Patients were excluded if they had a preoperative diagnosis of thyroid cancer or were on long-term preoperative calcitriol. Our primary outcome was permanent hypoparathyroidism, which was identified based on persistent use of calcitriol between 6-12 months following thyroidectomy. We used multivariable logistic regression to identify characteristics associated with permanent hypoparathyroidism, including patient age, sex, race/ethnicity, neighborhood disadvantage, Charlson-Deyo Comorbidity Index, urban or rural residence, and frailty.We identified 4,650 patients who underwent total thyroidectomy for GD during the study period and met inclusion criteria (mean age 72.8 years [SD 5.5], 86% female, and 79% white). Among this surgical cohort, 104 (2.2%, 95% CI: 1.8-2.7%) patients developed permanent hypoparathyroidism requiring calcitriol therapy. Patients who developed permanent hypoparathyroidism were on average older (mean age 74.1 vs. 72.8 years) than those who did not develop permanent hypoparathyroidism (p=0.04). On multivariable regression, older age was the only patient characteristic associated with permanent hypoparathyroidism (odds ratio [OR] age ≥ 76 years 1.68 [95% CI 1.13-2.51] compared to age 66-75 years).The risk of permanent hypoparathyroidism requiring calcitriol therapy among this national, U.S. population-based cohort of older adults with GD treated with total thyroidectomy was low, even when considering operations performed by a heterogeneous group of surgeons. These findings suggest the risk of hypoparathyroidism should not be a deterrent to operative management for GD in older adults who are appropriate surgical candidates.

  View details for DOI 10.1089/thy.2022.0140

  View details for PubMedID 36416252

• Prevalence of Apparent Treatment-Resistant Hypertension in Chronic Kidney Disease in Two Large US Health Care Systems CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY An, J., Kurella Tamura, M., Odden, M. C., Ni, L., Thomas, I., Montez-Rath, M. E., Sim, J. J. 2022; 17 (10): 1457-1466

  View details for DOI 10.2215/CJN.04110422

  View details for Web of Science ID 000863522000007

• Prevalence of Apparent Treatment-Resistant Hypertension in Chronic Kidney Disease in Two Large US Health Care Systems. Clinical journal of the American Society of Nephrology : CJASN An, J., Kurella Tamura, M., Odden, M. C., Ni, L., Thomas, I. C., Montez-Rath, M. E., Sim, J. J. 2022; 17 (10): 1457-1466

  Abstract

  More intensive BP goals have been recommended for patients with CKD. We estimated the prevalence of apparent treatment-resistant hypertension among patients with CKD according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA; BP goal <130/80 mm Hg) and 2021 Kidney Disease Improving Global Outcomes (KDIGO; systolic BP <120 mm Hg) guidelines in two US health care systems.We included adults with CKD (an eGFR <60 ml/min per 1.73 m2) and treated hypertension from Kaiser Permanente Southern California and the Veterans Health Administration. Using electronic health records, we identified apparent treatment-resistant hypertension on the basis of (1) BP above the goal while prescribed three or more classes of antihypertensive medications or (2) prescribed four or more classes of antihypertensive medications regardless of BP. In a sensitivity analysis, we required diuretic use to be classified as apparent treatment-resistant hypertension. We estimated the prevalence of apparent treatment-resistant hypertension per clinical guideline and by CKD stage.Among 44,543 Kaiser Permanente Southern California and 241,465 Veterans Health Administration patients with CKD and treated hypertension, the prevalence rates of apparent treatment-resistant hypertension were 39% (Kaiser Permanente Southern California) and 35% (Veterans Health Administration) per the 2017 ACC/AHA guideline and 48% (Kaiser Permanente Southern California) and 55% (Veterans Health Administration) per the 2021 KDIGO guideline. By requiring a diuretic as a criterion for apparent treatment-resistant hypertension, the prevalence rates of apparent treatment-resistant hypertension were lowered to 31% (Kaiser Permanente Southern California) and 23% (Veterans Health Administration) per the 2017 ACC/AHA guideline. The prevalence rates of apparent treatment-resistant hypertension were progressively higher at more advanced stages of CKD (34%/33%, 42%/36%, 52%/41%, and 60%/37% for Kaiser Permanente Southern California/Veterans Health Administration eGFR 45-59, 30-44, 15-29, and <15 ml/min per 1.73 m2, respectively) per the 2017 ACC/AHA guideline.Depending on the CKD stage, up to a half of patients with CKD met apparent treatment-resistant hypertension criteria.

  View details for DOI 10.2215/CJN.04110422

  View details for PubMedID 36400564

• Implementation and Effectiveness of a Learning Collaborative to Improve Palliative Care for Seriously Ill Hemodialysis Patients. Clinical journal of the American Society of Nephrology : CJASN Kurella Tamura, M., Holdsworth, L., Stedman, M., Aldous, A., Asch, S. M., Han, J., Harbert, G., Lorenz, K. A., Malcolm, E., Nicklas, A., Moss, A. H., Lupu, D. E. 2022

  Abstract

  BACKGROUND AND OBJECTIVES: Limited implementation of palliative care practices in hemodialysis may contribute to end-of-life care that is intensive and not patient centered. We determined whether a learning collaborative for hemodialysis center providers improved delivery of palliative care best practices.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Ten US hemodialysis centers participated in a pre-post study targeting seriously ill patients between April 2019 and September 2020. Three practices were prioritized: screening for serious illness, goals of care discussions, and use of a palliative dialysis care pathway. The collaborative educational bundle consisted of learning sessions, communication skills training, and implementation support. The primary outcome was change in the probability of complete advance care planning documentation among seriously ill patients. Health care utilization was a secondary outcome, and implementation outcomes of acceptability, adoption, feasibility, and penetration were assessed using mixed methods.RESULTS: One center dropped out due to the coronavirus disease 2019 pandemic. Among the remaining nine centers, 20% (273 of 1395) of patients were identified as seriously ill preimplementation, and 16% (203 of 1254) were identified as seriously ill postimplementation. From the preimplementation to postimplementation period, the adjusted probability of complete advance care planning documentation among seriously ill patients increased by 34.5 percentage points (95% confidence interval, 4.4 to 68.5). There was no difference in mortality or in utilization of palliative hemodialysis, hospice referral, or hemodialysis discontinuation. Screening for serious illness was widely adopted, and goals of care discussions were adopted with incomplete integration. There was limited adoption of a palliative dialysis care pathway.CONCLUSIONS: A learning collaborative for hemodialysis centers spanning the coronavirus disease 2019 pandemic was associated with adoption of serious illness screening and goals of care discussions as well as improved documentation of advance care planning for seriously ill patients.CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Pathways Project: Kidney Supportive Care, NCT04125537.

  View details for DOI 10.2215/CJN.00090122

  View details for PubMedID 36104084

• Adverse Cardiovascular Outcomes Among Older Adults with Primary Hyperparathyroidism Treated with Parathyroidectomy vs. non-operative Management. Annals of surgery Seib, C. D., Meng, T., Cisco, R. M., Suh, I., Lin, D. T., Harris, A. H., Trickey, A. W., Tamura, M. K., Kebebew, E. 2022

  Abstract

  We sought to compare the incidence of adverse cardiovascular events in older adults with primary hyperparathyroidism (PHPT) treated with parathyroidectomy versus non-operative management.PHPT is a common endocrine disorder that is associated with increased cardiovascular mortality, but it is not known whether parathyroidectomy reduces the incidence of adverse cardiovascular events.We conducted a population-based, longitudinal cohort study of Medicare beneficiaries diagnosed with PHPT (2006-2017). Multivariable, inverse probability weighted Cox proportional hazards regression was used to determine the associations of parathyroidectomy with major adverse cardiovascular events (MACE), cardiovascular disease-related hospitalization, and cardiovascular hospitalization-associated mortality.We identified 210,206 beneficiaries diagnosed with PHPT from 2006-2017. Among 63,136 (30.0%) treated with parathyroidectomy and 147,070 (70.0%) managed non-operatively within one year of diagnosis, the unadjusted incidence of MACE was 10.0% (mean follow-up 59.1 [SD 35.6] months) and 11.5% (mean follow-up 54.1 [SD 34.0] months), respectively. In multivariable analysis, parathyroidectomy was associated with a lower incidence of MACE (HR 0.92 [95%CI 0.90-0.94]), cardiovascular disease-related hospitalization (HR 0.89 [95%CI 0.87-0.91]), and cardiovascular hospitalization-associated mortality (HR 0.76 [95%CI 0.71-0.81]) compared to non-operative management. At 10 years, parathyroidectomy was associated with adjusted absolute risk reduction for MACE of 1.7% (95%CI 1.3%-2.1%), for cardiovascular disease-related hospitalization of 2.5% (95%CI 2.1%-2.9%), and for cardiovascular hospitalization-associated mortality of 1.4% (95%CI 1.2%-1.6%).In this large, population-based cohort study, parathyroidectomy was associated with a lower long-term incidence of adverse cardiovascular outcomes when compared with non-operative management for older adults with PHPT, which is relevant to surgical decision-making for patients with a long life expectancy.

  View details for DOI 10.1097/SLA.0000000000005691

  View details for PubMedID 36005546

• Vitamin K Status and Cognitive Function in Adults with Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort. Current developments in nutrition Shea, M. K., Wang, J., Barger, K., Weiner, D. E., Booth, S. L., Seliger, S. L., Anderson, A. H., Deo, R., Feldman, H. I., Go, A. S., He, J., Ricardo, A. C., Tamura, M. K. 2022; 6 (8): nzac111

  Abstract

  Vitamin K is linked to cognitive function, but studies in individuals with chronic kidney disease (CKD), who are at risk for vitamin K insufficiency and cognitive impairment, are lacking. The cross-sectional association of vitamin K status biomarkers with cognitive performance was evaluated in ≥55-y-old adults with CKD (N = 714, 49% female, 44% black). A composite score of a cognitive performance test battery, calculated by averaging the z scores of the individual tests, was the primary outcome. Vitamin K status was measured using plasma phylloquinone and dephospho-uncarboxylated matrix Gla protein [(dp)ucMGP]. Participants with low plasma (dp)ucMGP, reflecting higher vitamin K status, had better cognitive performance than those in the two higher (dp)ucMGP categories based on the composite outcome (P = 0.03), whereas it did not significantly differ according to plasma phylloquinone categories (P = 0.08). Neither biomarker was significantly associated with performance on individual tests (all P > 0.05). The importance of vitamin K to cognitive performance in adults with CKD remains to be clarified.

  View details for DOI 10.1093/cdn/nzac111

  View details for PubMedID 35957738

  View details for PubMedCentralID PMC9362761

• The Impact of Care Partners on the Mobility of Older Adults Receiving Hemodialysis. Kidney medicine Liu, C. K., Seo, J., Lee, D., Wright, K., Tamura, M. K., Moye, J., Weiner, D. E., Bean, J. F. 2022; 4 (6): 100473

  Abstract

  Rationale & Objective: Many older adults receiving hemodialysis have mobility limitations and rely on care partners, yet data are sparse regarding the support provided by care partners. Our aim was to examine how care partners support the mobility of an older adult receiving hemodialysis.Study Design: Qualitative study.Setting & Participants: Using purposive sampling, we recruited persons aged 60 years or more receiving maintenance hemodialysis and care partners aged 18 years or more who were providing support to an older adult receiving hemodialysis. We conducted in-person semi-structured interviews about mobility with each individual.Analytical Approach: We conducted descriptive and focused coding of interview transcripts and employed thematic analysis. Our outcome was to describe perceived mobility supports provided by care partners using qualitative themes.Results: We enrolled 31 older adults receiving hemodialysis (42% women, 68% Black) with a mean age of 73±8 years and a mean dialysis duration of 4.6±3.5 years. Of these, 87% of patients used assistive devices and 90% had care partners. We enrolled 12 care partners (75% women, 33% Black) with a mean age of 54±16 years. From our patient and care partner interviews, we found three themes: (1) what care partners see, (2) what care partners do, and (3) what care partners feel. Regarding what they see, care partners witness a decline in patient mobility. Regarding what they do, care partners guide and facilitate activities and manage others who also assist. Regarding what they feel, care partners respect the patient's autonomy but experience frustration and worry about the patient's future mobility.Limitations: Modest sample size; single geographic area.Conclusions: In older adults receiving hemodialysis, care partners observe a decline in mobility and provide support for mobility. They respect the patient's autonomy but worry about future mobility losses. Future research should incorporate care partners in interventions that address mobility in older adults receiving hemodialysis.

  View details for DOI 10.1016/j.xkme.2022.100473

  View details for PubMedID 35663231

• Association of Proximal Tubular Secretory Clearance with Long-Term Decline in Cognitive Function. Journal of the American Society of Nephrology : JASN Lidgard, B., Bansal, N., Zelnick, L., Hoofnagle, A., Chen, J., Colaizzo, D., Dobre, M., Mills, K., Porter, A., Rosas, S., Sarnak, M., Seliger, S., Sondheimer, J., Kurella Tamura, M., Yaffe, K., Kestenbaum, B. 2022

  Abstract

  Background Persons with chronic kidney disease (CKD) are at high risk for cognitive impairment and progressive cognitive decline. Retention of protein-bound organic solutes that are normally removed by tubular secretion is hypothesized to contribute to cognitive impairment in CKD. Methods We followed 2362 participants who were initially free of cognitive impairment and stroke in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study. We estimated tubular secretory clearance by the 24-hour kidney clearances of eight endogenous solutes that are primarily eliminated by tubular secretion. CRIC study investigators assessed participants' cognitive function annually, using the Modified Mini-Mental State (3MS) Examination. Cognitive decline was defined as a sustained >5 point decrease in the 3MS score from baseline. Using Cox regression models adjusted for potential confounders, we analyzed associations between secretory solute clearances, serum solute concentrations, and cognitive decline. Results The median number of follow-up 3MS examinations was 6 per participant. There were 247 incident cognitive decline events over a median of 9.1 years of follow-up. Lower kidney clearances of five of the eight secretory solutes (cinnamoylglycine, isovalerylglycine, kynurenic acid, pyridoxic acid, and tiglylglycine) were associated with cognitive decline after adjustment for baseline eGFR, proteinuria, and other confounding variables. Effect sizes ranged from a 17% to 34% higher risk of cognitive decline per 50% lower clearance. In contrast, serum concentrations of the solutes were not associated with cognitive decline. Conclusions Lower kidney clearances of secreted solutes are associated with incident global cognitive decline in a prospective study of CKD, independent of eGFR. Further work is needed to determine the domains of cognition most affected by decreased secretory clearance and the mechanisms of these associations.

  View details for DOI 10.1681/ASN.2021111435

  View details for PubMedID 35444055

• Video Images about Decisions for Ethical Outcomes in Kidney Disease (VIDEO-KD): the study protocol for a multi-centre randomised controlled trial. BMJ open Eneanya, N. D., Lakin, J. R., Paasche-Orlow, M. K., Lindvall, C., Moseley, E. T., Henault, L., Hanchate, A. D., Mandel, E. I., Wong, S. P., Zupanc, S. N., Davis, A. D., El-Jawahri, A., Quintiliani, L. M., Chang, Y., Waikar, S. S., Bansal, A. D., Schell, J. O., Lundquist, A. L., Tamura, M. K., Yu, M. K., Unruh, M. L., Argyropoulos, C., Germain, M. J., Volandes, A. 2022; 12 (4): e059313

  Abstract

  INTRODUCTION: Older patients with advanced chronic kidney disease (CKD) often are inadequately prepared to make informed decisions about treatments including dialysis and cardiopulmonary resuscitation. Further, evidence shows that patients with advanced CKD do not commonly engage in advance care planning (ACP), may suffer from poor quality of life, and may be exposed to end-of-life care that is not concordant with their goals. We aim to study the effectiveness of a video intervention on ACP, treatment preferences and other patient-reported outcomes.METHODS AND ANALYSIS: The Video Images about Decisions for Ethical Outcomes in Kidney Disease trial is a multi-centre randomised controlled trial that will test the effectiveness of an intervention that includes a CKD-related video decision aid followed by recording personal video declarations about goals of care and treatment preferences in older adults with advancing CKD. We aim to enrol 600 patients over 5 years at 10 sites.ETHICS AND DISSEMINATION: Regulatory and ethical aspects of this trial include a single Institutional Review Board mechanism for approval, data use agreements among sites, and a Data Safety and Monitoring Board. We intend to disseminate findings at national meetings and publish our results.TRIAL REGISTRATION NUMBER: NCT04347629.

  View details for DOI 10.1136/bmjopen-2021-059313

  View details for PubMedID 35396311

• Kidney stone events following parathyroidectomy vs. non-operative management for primary hyperparathyroidism. The Journal of clinical endocrinology and metabolism Seib, C. D., Ganesan, C., Arnow, K. D., Pao, A. C., Leppert, J. T., Barreto, N. B., Kebebew, E., Tamura, M. K. 2022

  Abstract

  CONTEXT: Primary hyperparathyroidism (PHPT) is associated with an increased risk of kidney stones. Few studies account for PHPT severity or stone risk when comparing stone events after parathyroidectomy vs. non-operative management.OBJECTIVE: Compare the incidence of kidney stone events in PHPT patients treated with parathyroidectomy vs. non-operative management.DESIGN: Longitudinal cohort study with propensity score inverse probability weighting and multivariable Cox proportional hazards regression.SETTING: Veterans Health Administration integrated health care system.PATIENTS: 44,978 patients with >2 years follow-up after PHPT diagnosis (2000-2018). 5,244 patients (11.7%) were treated with parathyroidectomy.MAIN OUTCOMES MEASURE: Clinically significant kidney stone event.RESULTS: The cohort had a mean age of 66.0 years, was 87.8% male, 66.4% White. Patients treated with parathyroidectomy had higher mean serum calcium (11.2 vs. 10.8mg/dL) and were more likely to have a history of kidney stone events. Among patients with baseline history of kidney stones, the unadjusted incidence of ≥1 kidney stone event was 30.5% in patients managed with parathyroidectomy (mean follow-up 5.6 years) compared to 18.0% in those managed non-operatively (mean follow-up 5.0 years). Patients treated with parathyroidectomy had a higher adjusted hazard of recurrent kidney stone events (hazard ratio[HR] 1.98, 95%CI 1.56-2.51); however, this association declined over time (parathyroidectomy*time HR 0.80, 95%CI 0.73-0.87).CONCLUSION: In this predominantly male cohort with PHPT, patients treated with parathyroidectomy continued to be at higher risk of kidney stone events in the immediate years after treatment than patients managed non-operatively, although the adjusted risk of stone events declined with time, suggesting a benefit to surgical treatment.

  View details for DOI 10.1210/clinem/dgac193

  View details for PubMedID 35363858

• Association of Intensive vs Standard Blood Pressure Control With Cerebral Blood Flow: Secondary Analysis of the SPRINT MIND Randomized Clinical Trial. JAMA neurology Dolui, S., Detre, J. A., Gaussoin, S. A., Herrick, J. S., Wang, D. J., Tamura, M. K., Cho, M. E., Haley, W. E., Launer, L. J., Punzi, H. A., Rastogi, A., Still, C. H., Weiner, D. E., Wright, J. T., Williamson, J. D., Wright, C. B., Bryan, R. N., Bress, A. P., Pajewski, N. M., Nasrallah, I. M. 2022

  Abstract

  Importance: Antihypertensive treatments benefit cerebrovascular health and cognitive function in patients with hypertension, but it is uncertain whether an intensive blood pressure target leads to potentially harmful cerebral hypoperfusion.Objective: To investigate the association of intensive systolic blood pressure (SBP) control vs standard control with whole-brain cerebral blood flow (CBF).Design, Setting, and Participants: This substudy of the Systolic Blood Pressure Intervention Trial (SPRINT) randomized clinical trial compared the efficacy of 2 different blood pressure-lowering strategies with longitudinal brain magnetic resonance imaging (MRI) including arterial spin labeled perfusion imaging to quantify CBF. A total of 1267 adults 50 years or older with hypertension and increased cardiovascular risk but free of diabetes or dementia were screened for the SPRINT substudy from 6 sites in the US. Randomization began in November 2010 with final follow-up MRI in July 2016. Analyses were performed from September 2020 through December 2021.Interventions: Study participants with baseline CBF measures were randomized to an intensive SBP target less than 120 mm Hg or standard SBP target less than 140 mm Hg.Main Outcomes and Measures: The primary outcome was change in whole-brain CBF from baseline. Secondary outcomes were change in gray matter, white matter, and periventricular white matter CBF.Results: Among 547 participants with CBF measured at baseline, the mean (SD) age was 67.5 (8.1) years and 219 (40.0%) were women; 315 completed follow-up MRI at a median (IQR) of 4.0 (3.7-4.1) years after randomization. Mean whole-brain CBF increased from 38.90 to 40.36 (difference, 1.46 [95% CI, 0.08-2.83]) mL/100 g/min in the intensive treatment group, with no mean increase in the standard treatment group (37.96 to 37.12; difference, -0.84 [95% CI, -2.30 to 0.61] mL/100 g/min; between-group difference, 2.30 [95% CI, 0.30-4.30; P=.02]). Gray, white, and periventricular white matter CBF showed similar changes. The association of intensive vs standard treatment with CBF was generally similar across subgroups defined by age, sex, race, chronic kidney disease, SBP, orthostatic hypotension, and frailty, with the exception of an indication of larger mean increases in CBF associated with intensive treatment among participants with a history of cardiovascular disease (interaction P=.05).Conclusions and Relevance: Intensive vs standard antihypertensive treatment was associated with increased, rather than decreased, cerebral perfusion, most notably in participants with a history of cardiovascular disease.Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

  View details for DOI 10.1001/jamaneurol.2022.0074

  View details for PubMedID 35254390

• The Relationship of Kidney Tubule Biomarkers with Brain Imaging in CKD Patients in SPRINT. Kidney360 Miller, L. M., Kurella Tamura, M., Pajewski, N. M., Rifkin, D., Weiner, D., Marquine, M., Shlipak, M. G., Ix, J. H. 2022; 3 (2): 337-340

  Abstract

  Urine biomarker concentrations reflecting kidney tubule injury and dysfunction were not associated with brain MRI measures.Higher eGFR was associated with lower total brain cerebral blood flow.This is the first evaluation of the relationship of kidney tubule biomarkers with brain imaging by MRI in patients with CKD.

  View details for DOI 10.34067/KID.0007702021

  View details for PubMedID 35373134

• Risk of Fracture Among Older Adults With Primary Hyperparathyroidism Receiving Parathyroidectomy vs Nonoperative Management. JAMA internal medicine Seib, C. D., Meng, T., Suh, I., Harris, A. H., Covinsky, K. E., Shoback, D. M., Trickey, A. W., Kebebew, E., Tamura, M. K. 2021

  Abstract

  Importance: Primary hyperparathyroidism (PHPT) contributes to the development and progression of osteoporosis in older adults. The effectiveness of parathyroidectomy for reducing fracture risk in older adults is unknown.Objective: To compare the incidence of clinical fracture among older adults with PHPT treated with parathyroidectomy vs nonoperative management.Design, Setting, and Participants: This was a population-based, longitudinal cohort study of all Medicare beneficiaries with PHPT from 2006 to 2017. Multivariable, inverse probability weighted Cox proportional hazards and Fine-Gray competing risk regression models were constructed to determine the association of parathyroidectomy vs nonoperative management with incident fracture. Data analysis was conducted from February 17, 2021, to September 14, 2021.Main Outcomes and Measures: The primary outcome was clinical fracture at any anatomic site not associated with major trauma during the follow-up period.Results: Among the 210 206 Medicare beneficiaries with PHPT (mean [SD] age, 75 [6.8] years; 165 637 [78.8%] women; 183 433 [87.3%] White individuals), 63 136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis, and 147 070 (70.0%) were managed nonoperatively. During a mean (SD) follow-up period of 58.5 (35.5) months, the unadjusted incidence of fracture was 10.2% in patients treated with parathyroidectomy. During a mean (SD) follow-up of 52.5 (33.8) months, the unadjusted incidence of fracture was 13.7% in patients observed nonoperatively. On multivariable analysis, parathyroidectomy was associated with lower adjusted rates of any fracture (hazard ratio [HR], 0.78; 95% CI, 0.76-0.80]) and hip fracture (HR, 0.76; 95% CI, 0.72-0.79). At 2, 5, and 10 years, parathyroidectomy was associated with adjusted absolute fracture risk reduction of 1.2% (95% CI, 1.0-1.4), 2.8% (95% CI, 2.5-3.1), and 5.1% (95% CI, 4.6-5.5), respectively, compared with nonoperative management. On subgroup analysis, there were no significant differences in the association of parathyroidectomy with fracture risk by age group, sex, frailty, history of osteoporosis, or meeting operative guidelines. Fine-Gray competing risk regression confirmed parathyroidectomy was associated with a lower probability of any fracture and hip fracture when accounting for the competing risk of death (HR, 0.84; 95% CI, 0.82-0.85; and HR, 0.83; 95% CI, 0.80-0.85, respectively).Conclusions and Relevance: This longitudinal cohort study found that parathyroidectomy was associated with a lower risk of any fracture and hip fracture among older adults with PHPT, suggesting a clinically meaningful benefit of operative management in this population.

  View details for DOI 10.1001/jamainternmed.2021.6437

  View details for PubMedID 34842909

• Plasma amyloid beta, neurofilament light chain, and total tau in the Systolic Blood Pressure Intervention Trial (SPRINT). Alzheimer's & dementia : the journal of the Alzheimer's Association Pajewski, N. M., Elahi, F. M., Tamura, M. K., Hinman, J. D., Nasrallah, I. M., Ix, J. H., Miller, L. M., Launer, L. J., Wright, C. B., Supiano, M. A., Lerner, A. J., Sudduth, T. L., Killeen, A. A., Cheung, A. K., Reboussin, D. M., Wilcock, D. M., Williamson, J. D. 2021

  Abstract

  INTRODUCTION: Lowering blood pressure (BP) reduces the risk for cognitive impairment and the progression of cerebral white matter lesions. It is unclear whether hypertension control also influences plasma biomarkers related to Alzheimer's disease and non-disease-specific neurodegeneration.METHODS: We examined the effect of intensive (<120mm Hg) versus standard (<140mm Hg) BP control on longitudinal changes in plasma amyloid beta (Abeta)40 and Abeta42 , total tau, and neurofilament light chain (NfL) in a subgroup of participants from the Systolic Blood Pressure Intervention Trial (N=517).RESULTS: Over 3.8 years, there were no significant between-group differences for Abeta40, Abeta42, Abeta42 /Abeta40, or total tau. Intensive treatment was associated with larger increases in NfL compared to standard treatment. Adjusting for kidney function, but not BP, attenuated the association between intensive treatment and NfL.DISCUSSION: Intensive BP treatment was associated with changes in NfL, which were correlated with changes in kidney function associated with intensive treatment.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01206062.

  View details for DOI 10.1002/alz.12496

  View details for PubMedID 34786815

• Family Members' Understanding of the End-of-Life Wishes of People Undergoing Maintenance Dialysis. Clinical journal of the American Society of Nephrology : CJASN Saeed, F., Butler, C. R., Clark, C., O'Loughlin, K., Engelberg, R. A., Hebert, P. L., Lavallee, D. C., Vig, E. K., Tamura, M. K., Curtis, J. R., O'Hare, A. M. 2021; 16 (11): 1630-1638

  Abstract

  BACKGROUND AND OBJECTIVES: People receiving maintenance dialysis must often rely on family members and other close persons to make critical treatment decisions toward the end of life. Contemporary data on family members' understanding of the end-of-life wishes of members of this population are lacking.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 172 family members of people undergoing maintenance dialysis, we ascertained their level of involvement in the patient's care and prior discussions about care preferences. We also compared patient and family member responses to questions about end-of-life care using percentage agreement and the kappa-statistic.RESULTS: The mean (SD) age of the 172 enrolled family members was 55 (±17) years, 136 (79%) were women, and 43 (25%) were Black individuals. Sixty-seven (39%) family members were spouses or partners of enrolled patients. A total of 137 (80%) family members had spoken with the patient about whom they would want to make medical decisions, 108 (63%) had spoken with the patient about their treatment preferences, 47 (27%) had spoken with the patient about stopping dialysis, and 56 (33%) had spoken with the patient about hospice. Agreement between patient and family member responses was highest for the question about whether the patient would want cardiopulmonary resuscitation (percentage agreement 83%, kappa=0.31), and was substantially lower for questions about a range of other aspects of end-of-life care, including preference for mechanical ventilation (62%, 0.21), values around life prolongation versus comfort (45%, 0.13), preferred place of death (58%, 0.07), preferred decisional role (54%, 0.15), and prognostic expectations (38%, 0.15).CONCLUSIONS: Most surveyed family members reported they had spoken with the patient about their end-of-life preferences but not about stopping dialysis or hospice. Although family members had a fair understanding of patients' cardiopulmonary resuscitation preferences, most lacked a detailed understanding of their perspectives on other aspects of end-of-life care.

  View details for DOI 10.2215/CJN.04860421

  View details for PubMedID 34507967

• Mobility in Older Adults Receiving Maintenance Hemodialysis: A Qualitative Study. American journal of kidney diseases : the official journal of the National Kidney Foundation Liu, C. K., Seo, J., Lee, D., Wright, K., Tamura, M. K., Moye, J. A., Bean, J. F., Weiner, D. E. 2021

  Abstract

  RATIONALE & OBJECTIVE: For older adults, maintaining mobility is a major priority, especially for those with advanced chronic diseases like kidney failure. However, our understanding of the factors affecting mobility in older adults receiving maintenance hemodialysis is limited.STUDY DESIGN: Descriptive qualitative study.SETTING AND PARTICIPANTS: Using purposive sampling, we recruited 1) persons aged ≥ 60 years receiving maintenance hemodialysis and 2) care partners (≥ 18 years) providing regular support to an older adult receiving hemodialysis. During a single in-person home visit, we assessed mobility using the Short Physical Performance Battery (SPPB) and conducted individual one-on-one interviews regarding important personal factors related to mobility.ANALYTIC APPROACH: Descriptive statistics were used for demographic and SPPB data. Transcripts underwent thematic coding, informed by the International Classification of Function framework of mobility. We used conceptual content analysis to inductively extract themes and subthemes.RESULTS: We enrolled 31 older adults receiving hemodialysis (42% female, 68% Black) with mean age of 73±8 years and mean dialysis duration of 4.6±3.5 years; mean SPPB was 3.6±2.8 points. Among 12 care partners (75% female, 33% Black), mean age was 54±16 years and mean SPPB was 10.1±2.4 points. Major themes extracted were: 1) mobility represents independence; 2) mobility is precarious; 3) limitations in mobility cause distress; 4) sources of encouragement and motivation are critical; and 5) adaptability is key.LIMITATIONS: Modest sample from single geographic area.CONCLUSIONS: For older adults receiving hemodialysis, mobility is severely limited and is often precarious in nature, causing distress. Older adults receiving hemodialysis and their care partners have identified sources of encouragement and motivation for mobility, and cite an adaptable mindset as important. Future studies should conceptualize mobility as a variable condition, and build upon this outlook of adaptability in the development of interventions.

  View details for DOI 10.1053/j.ajkd.2021.07.010

  View details for PubMedID 34419517

• Nephrology Referral Based on Laboratory Values, Kidney Failure Risk, or Both: A Study Using Veterans Affairs Health System Data. American journal of kidney diseases : the official journal of the National Kidney Foundation Duggal, V., Montez-Rath, M. E., Thomas, I., Goldstein, M. K., Tamura, M. K. 2021

  Abstract

  RATIONALE AND OBJECTIV: Current guidelines for nephrology referral are based on laboratory criteria. We sought to evaluate whether nephrology referral patterns reflect current clinical practice guidelines and to estimate change in referral volume if they were based on the estimated risk of kidney failure.STUDY DESIGN: Observational cohort.SETTING AND PARTICIPANTS: Retrospective study of 399,644 veterans with chronic kidney disease (October 1, 2015 -September 30, 2016).EXPOSURES: Laboratory referral criteria based on VA/Department of Defense guidelines, categories of predicted risk for kidney failure using the Kidney Failure Risk Equation, and the combination of laboratory referral criteria and predicted risk.OUTCOMES: Number of patients identified for referral.ANALYTICAL APPROACH: We evaluated the number of patients who were referred and their predicted two-year risk for kidney failure. For each exposure, we estimated the number of patients who would be identified for referral.RESULTS: There were 66,276 patients who met laboratory indications for referral. Among these patients, 11,752 (17.7%) were referred to nephrology in the following year. Median two-year predicted risk of kidney failure was 1.5% [25th-75th percentiles 0.3-4.7%] among all patients meeting laboratory referral criteria. If referral were restricted to patients with predicted risk ≥1% in addition to laboratory indications, potential referral volume would be reduced from 66,276 to 38,229 patients. If referrals were based on predicted risk alone, a two-year risk threshold of 1% or higher would identify a similar number of patients (N=72,948) as laboratory-based criteria with median predicted risk of 2.3% [1.4-4.6%].LIMITATIONS: Missing proteinuria measurements.CONCLUSIONS: Current laboratory based guidelines for nephrology referral identify patients who are, on average, at low risk for progression, most of whom are not referred. As an alternative, referral based on a two-year kidney failure risk exceeding 1% would identify a similar number of patients but with a higher median risk of kidney failure.

  View details for DOI 10.1053/j.ajkd.2021.06.028

  View details for PubMedID 34450193

• Association Between Self-reported Importance of Religious or Spiritual Beliefs and End-of-Life Care Preferences Among People Receiving Dialysis JAMA NETWORK OPEN Scherer, J. S., Milazzo, K. C., Hebert, P. L., Engelberg, R. A., Lavallee, D. C., Vig, E. K., Kurella Tamura, M., Roberts, G., Curtis, J., O'Hare, A. M. 2021; 4 (8): e2119355

  Abstract

  Although people receiving maintenance dialysis have limited life expectancy and a high burden of comorbidity, relatively few studies have examined spirituality and religious beliefs among members of this population.To examine whether there is an association between the importance of religious or spiritual beliefs and care preferences and palliative care needs in people who receive dialysis.A cross-sectional survey study was conducted among adults who were undergoing maintenance dialysis at 31 facilities in Seattle, Washington, and Nashville, Tennessee, between April 22, 2015, and October 2, 2018. The survey included a series of questions assessing patients' knowledge, preferences, values, and expectations related to end-of-life care. Data were analyzed from February 12, 2020, to April 21, 2021.The importance of religious or spiritual beliefs was ascertained by asking participants to respond to this statement: "My religious or spiritual beliefs are what really lie behind my whole approach to life." Response options were definitely true, tends to be true, tends not to be true, or definitely not true.Outcome measures were based on self-reported engagement in advance care planning, resuscitation preferences, values regarding life prolongation, preferred place of death, decision-making preference, thoughts or discussion about hospice or stopping dialysis, prognostic expectations, and palliative care needs.A total of 937 participants were included in the cohort, of whom the mean (SD) age was 62.8 (13.8) years and 524 (55.9%) were men. Overall, 435 (46.4%) participants rated the statement about religious or spiritual beliefs as definitely true, 230 (24.6%) rated it as tends to be true, 137 (14.6%) rated it as tends not to be true, and 135 (14.4%) rated it as definitely not true. Participants for whom these beliefs were more important were more likely to prefer cardiopulmonary resuscitation (estimated probability for definitely true: 69.8% [95% CI, 66.5%-73.2%]; tends to be true: 60.8% [95% CI, 53.4%-68.3%]; tends not to be true: 61.6% [95% CI, 53.6%-69.6%]; and definitely not true: 60.6% [95% CI, 52.5%-68.6%]; P for trend = .003) and mechanical ventilation (estimated probability for definitely true: 42.6% [95% CI, 38.1%-47.0%]; tends to be true: 33.5% [95% CI, 25.9%-41.2%]; tends not to be true: 35.1% [95% CI, 27.2%-42.9%]; and definitely not true: 27.9% [95% CI, 19.6%-36.1%]; P for trend = .002) and to prefer a shared role in decision-making (estimated probability for definitely true: 41.6% [95% CI, 37.7%-45.5%]; tends to be true: 35.4% [95% CI, 29.0%-41.8%]; tends not to be true: 36.0% [95% CI, 26.7%-45.2%]; and definitely not true: 23.8% [95% CI, 17.3%-30.3%]; P for trend = .001) and were less likely to have thought or spoken about stopping dialysis. These participants were no less likely to have engaged in advance care planning, to value relief of pain and discomfort, to prefer to die at home, to have ever thought or spoken about hospice, and to have unmet palliative care needs and had similar prognostic expectations.The finding that religious or spiritual beliefs were important to most study participants suggests the value of an integrative approach that addresses these beliefs in caring for people who receive dialysis.

  View details for DOI 10.1001/jamanetworkopen.2021.19355

  View details for Web of Science ID 000681774200005

  View details for PubMedID 34347059

  View details for PubMedCentralID PMC8339933

• Racial disparities in the utilization of parathyroidectomy among patients with primary hyperparathyroidism: Evidence from a nationwide analysis of Medicare claims. Surgery Alobuia, W. M., Meng, T., Cisco, R. M., Lin, D. T., Suh, I., Tamura, M. K., Trickey, A. W., Kebebew, E., Seib, C. D. 2021

  Abstract

  BACKGROUND: Among patients with primary hyperparathyroidism, parathyroidectomy offers a chance of cure and mitigation of disease-related complications. The impact of race/ethnicity on referral and utilization of parathyroidectomy has not been fully explored.METHODS: Population-based, retrospective cohort study using 100% Medicare claims from beneficiaries with primary hyperparathyroidism from 2006 to 2016. Associations of race/ethnicity with disease severity, surgeon evaluation, and subsequent parathyroidectomy were analyzed using adjusted multivariable logistic regression models.RESULTS: Among 210,206 beneficiaries with primary hyperparathyroidism, 63,136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis. Black patients were more likely than other races/ethnicities to have stage 3 chronic kidney disease (10.8%) but had lower prevalence of osteoporosis and nephrolithiasis compared to White patients, Black and Hispanic patients were more likely to have been hospitalized for primaryhyperparathyroidism-associated conditions (White 4.8%, Black 8.1%, Hispanic 5.8%; P < .001). Patients who were White and met operative criteria were more likely to undergo parathyroidectomy than Black, Hispanic, or Asian patients (White 30.5%, Black 23.0%, Hispanic 21.4%, Asian 18.7%; P < .001). Black and Hispanicpatients had lower adjusted odds of being evaluated by a surgeon (odds ratios 0.71 [95% confidenceinterval 0.69-0.74], 0.68 [95% confidence interval 0.61-0.74], respectively) and undergoing parathyroidectomy if evaluated by a surgeon (odds ratios 0.72 [95% confidence interval 0.68-0.77], 0.82 [95%confidence interval 0.67-0.99]). Asian race was associated with lower adjusted odds of being evaluated by a surgeon (odds ratio 0.64 [95% confidence interval 0.57-0.71]), but no difference in odds of parathyroidectomy.CONCLUSION: Racial/ethnic disparities exist in the management of primary hyperparathyroidism among older adults. Determining the factors that account for this disparity require urgent attention to achieve parity in the management of primary hyperparathyroidism.

  View details for DOI 10.1016/j.surg.2021.05.037

  View details for PubMedID 34229901

• Association of parathyroidectomy with 5-year clinically significant kidney stone events in patients with primary hyperparathyroidism. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists Seib, C. D., Ganesan, C., Arnow, K. D., Suh, I., Pao, A. C., Leppert, J. T., Tamura, M. K., Trickey, A. W., Kebebew, E. 2021

  Abstract

  OBJECTIVE: Patients with primary hyperparathyroidism (PHPT) are at increased risk of kidney stones. Guidelines recommend parathyroidectomy in PHPT patients with a history of stone disease. This study aimed to compare the 5-year incidence of clinically significant kidney stone events in patients with PHPT treated with parathyroidectomy vs. non-operative management.METHODS: We performed a longitudinal cohort study of patients with PHPT in a national commercial insurance claims database (2006-2019). Propensity score inverse probability weighting-adjusted multivariable regression models were calculated.RESULTS: We identified 7,623 patients ≥35 years-old with continuous enrollment >1 year before and >5 years after PHPT diagnosis. 2,933 patients (38.5%) were treated with parathyroidectomy. The cohort had a mean age of 66.5 years, 78.1% were female, 72.4% were White. Over 5 years, the unadjusted incidence of ≥1 kidney stone event was higher in patients managed with parathyroidectomy compared to those managed non-operatively overall (5.4% vs. 4.1%) and among those with a history of kidney stones at PHPT diagnosis (17.9% vs. 16.4%). On multivariable analysis, parathyroidectomy was associated with no statistically significant difference in the odds of 5-year kidney stone event among patients with a history of kidney stones (OR 1.03, 95%CI 0.71-1.50) or those without history of kidney stones (OR 1.16, 95%CI 0.84-1.60).CONCLUSION: Based on this claims analysis, there was no difference in the odds of 5-year kidney stone events in PHPT patients treated with parathyroidectomy vs. non-operative management. Time-horizon for benefit should be considered when making treatment decisions for PHPT based on risk of kidney stone events.

  View details for DOI 10.1016/j.eprac.2021.06.004

  View details for PubMedID 34126246

• Osteoporosis, Fractures, and Bone Mineral Density Screening in Veterans With Kidney Stone Disease. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Ganesan, C., Thomas, I., Romero, R., Song, S., Conti, S., Elliott, C., Chertow, G. M., Tamura, M. K., Leppert, J. T., Pao, A. C. 2021

  Abstract

  Whether a link exists between kidney stone disease and osteoporosis or fractures remains an open question. In this retrospective cohort study, we sought to determine the prevalence of osteoporosis and fractures and rate of bone mineral density screening by dual-energy X-ray absorptiometry (DXA) in patients with kidney stone disease. We examined nationwide data from the Veterans Health Administration and identified 531,431 patients with kidney stone disease between 2007 and 2015. Nearly 1 in 4 patients (23.6%, 95% confidence interval [CI] 23.5-23.7) with kidney stone disease had a prevalent diagnosis of osteoporosis or fracture. In patients with no prior history of osteoporosis or bone mineral density assessment before a kidney stone diagnosis, 9.1% were screened with DXA after their kidney stone diagnosis, of whom 20% were subsequently diagnosed with osteoporosis. Our findings provide support for wider use of bone mineral density screening in patients with kidney stone disease, including middle-aged and older men, a group less well recognized as at risk for osteoporosis or fractures. © 2021 American Society for Bone and Mineral Research (ASBMR).

  View details for DOI 10.1002/jbmr.4260

  View details for PubMedID 33655611

• Atrial Fibrillation and Longitudinal Change in Cognitive Function in CKD KIDNEY INTERNATIONAL REPORTS McCauley, M. D., Hsu, J. Y., Ricardo, A. C., Darbar, D., Kansal, M., Tamura, M., Feldman, H. I., Kusek, J. W., Taliercio, J. J., Rao, P. S., Shafi, T., He, J., Wang, X., Sha, D., Lamar, M., Go, A. S., Yaffe, K., Rahman, M., Townsend, R. R., McCauley, M. D., Hsu, J. Y., Ricardo, A. C., Darbar, D., Kansal, M., Tamura, M., Feldman, H. I., Kusek, J. W., Taliercio, J. J., Rao, P. S., Shafi, T., He, J., Wang, X., Sha, D., Lamar, M., Go, A. S., Yaffe, K., Lash, J. P., CRIC Study Investigators 2021; 6 (3): 669–74

  Abstract

  Studies in the general population suggest that atrial fibrillation (AF) is an independent risk factor for decline in cognitive function, but this relationship has not been examined in adults with chronic kidney disease (CKD). We investigated the association between incident AF and changes in cognitive function over time in this population.We studied a subgroup of 3254 adults participating in the Chronic Renal Insufficiency Cohort Study. Incident AF was ascertained by 12-lead electrocardiogram (ECG) obtained at a study visit and/or identification of a hospitalization with AF during follow-up. Cognitive function was assessed biennially using the Modified Mini-Mental State Exam. Linear mixed effects regression was used to evaluate the association between incident AF and longitudinal change in cognitive function. Compared with individuals without incident AF (n = 3158), those with incident AF (n = 96) were older, had a higher prevalence of cardiovascular disease and hypertension, and lower estimated glomerular filtration rate. After median follow-up of 6.8 years, we observed no significant multivariable association between incident AF and change in cognitive function test score.In this cohort of adults with CKD, incident AF was not associated with a decline in cognitive function.

  View details for DOI 10.1016/j.ekir.2020.12.023

  View details for Web of Science ID 000631874200015

  View details for PubMedID 33732981

  View details for PubMedCentralID PMC7938064

• Association of Urine Biomarkers of Kidney Tubular Injury and Dysfunction With Frailty Index and Cognitive Function in Persons with CKD in SPRINT. American journal of kidney diseases : the official journal of the National Kidney Foundation Miller, L. M., Rifkin, D., Lee, A. K., Tamura, M. K., Pajewski, N. M., Weiner, D. E., Al-Rousan, T., Shlipak, M., Ix, J. H. 2021

  Abstract

  RATIONALE AND OBJECTIVE: The associations of glomerular markers of kidney disease (eGFR and albuminuria) with frailty and cognition are well established. However, the relationship of kidney tubular injury and dysfunction with frailty and cognition are unknown.STUDY DESIGN: Observational cross-sectional study; SETTING: & Participants: 2,253 participants with eGFR < 60 ml/min/1.73m2 in the Systolic Blood Pressure Intervention Trial EXPOSURES: Eight urine biomarkers: Interleukin-18 [IL-18, pg/mL], kidney injury molecule-1 [KIM-1, pg/mL], neutrophil gelatinase-associated lipocalin [NGAL, ng/mL], chitinase-3-like protein-1 [YKL-40, pg/mL], monocyte chemoattractant protein-1 [MCP-1, pg/mL], alpha-1 microglobulin [alpha1M mg/g], beta-2 microglobulin [beta2M ng/mL], and uromodulin [Umod ng/mL].OUTCOMES: Frailty was measured using a previously validated frailty index (FI), categorized as fit (FI < 0.10), less fit (0.10 < FI < 0.21) and frail (FI > 0.21). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA).ANALYTICAL APPROACH: Associations between kidney tubule biomarkers with categorical FI were evaluated using multinomial logistic regression with the fit group as the reference. Cognitive function was evaluated using linear regression. Models were adjusted for demographic, behavioral and clinical variables including eGFR and urine albumin.RESULTS: Three of the 8 urine biomarkers of tubule injury and dysfunction were independently associated with FI. Each two-fold higher level of urine KIM-1, a marker of tubule injury, was associated with a 1.22 [95% CI: 1.01, 1.49) fold greater odds of being in frail group. MCP-1, a marker of tubulo-interstitial fibrosis, was associated with a 1.30 [95% CI 1.04, 1.64] greater odds of being in frail group, and alpha1M, a marker of tubule re-absorptive capacity, was associated with a 1.48 [95% CI 1.11, 1.96] greater odds. These associations were independent of confounders including eGFR and urine albumin, and were stronger than those of urine albumin with frailty index (1.15 [95% CI 0.99, 1.34]). Higher urine beta2M, another marker of tubule reabsorptive capacity, was associated with worse cognitive scores at baseline (beta: -0.09; 95% CI -0.17, -0.01). Urine albumin was not associated with cognitive function.LIMITATIONS: Cross-sectional design, FI may not be generalizable in other populations.CONCLUSIONS: Urine biomarkers of tubule injury, fibrosis and proximal tubule reabsorptive capacity are variably associated with FI and worse cognition, independent of glomerular markers of kidney health. Future studies are needed to validate these results among other patient populations.

  View details for DOI 10.1053/j.ajkd.2021.01.009

  View details for PubMedID 33647393

• Pathways Project: Development of a Multimodal Innovation To Improve Kidney Supportive Care in Dialysis Centers. Kidney360 Lupu, D. E., Aldous, A., Harbert, G., Kurella Tamura, M., Holdsworth, L. M., Nicklas, A., Vinson, B., Moss, A. H. 2021; 2 (1): 114-128

  Abstract

  Current care models for older patients with kidney failure in the United States do not incorporate supportive care approaches. The absence of supportive care contributes to poor symptom management and unwanted forms of care at the end of life. Using an Institute for Healthcare Improvement Collaborative Model for Achieving Breakthrough Improvement, we conducted a focused literature review, interviewed implementation experts, and convened a technical expert panel to distill existing evidence into an evidence-based supportive care change package. The change package consists of 14 best-practice recommendations for the care of patients seriously ill with kidney failure, emphasizing three key practices: systematic identification of patients who are seriously ill, goals-of-care conversations with identified patients, and care options to respond to patient wishes. Implementation will be supported through a collaborative consisting of three intensive learning sessions, monthly learning and collaboration calls, site data feedback, and quality-improvement technical assistance. To evaluate the change package's implementation and effectiveness, we designed a mixed-methods hybrid study involving the following: (1) effectiveness evaluation (including patient outcomes and staff perception of the effectiveness of the implementation of the change package); (2) quality-improvement monitoring via monthly tracking of a suite of quality-improvement indicators tied to the change package; and (3) implementation evaluation conducted by the external evaluator using mixed methods to assess implementation of the collaborative processes. Ten dialysis centers across the country, treating approximately 1550 patients, will participate. This article describes the process informing the intervention design, components of the intervention, evaluation design and measurements, and preliminary feasibility assessments.Pathways Project: Kidney Supportive Care, NCT04125537.

  View details for DOI 10.34067/KID.0005892020

  View details for PubMedID 35368811

  View details for PubMedCentralID PMC8785737

• Patient Factors Associated With Parathyroidectomy in Older Adults With Primary Hyperparathyroidism. JAMA surgery Seib, C. D., Suh, I., Meng, T., Trickey, A., Smith, A. K., Finlayson, E., Covinsky, K. E., Kurella Tamura, M., Kebebew, E. 2021

  Abstract

  Importance: Parathyroidectomy provides definitive management for primary hyperparathyroidism (PHPT), reducing the risk of subsequent fracture, nephrolithiasis, and chronic kidney disease (CKD), but its use among older adults in the US is unknown.Objective: To identify patient characteristics associated with the use of parathyroidectomy for the management of PHPT in older adults.Design, Setting, and Participants: This population-based, retrospective cohort study used 100% Medicare claims from beneficiaries with an initial diagnosis of PHPT from January 1, 2006, to December 31, 2016. Patients were considered to meet consensus guideline criteria for parathyroidectomy based on diagnosis codes indicating osteoporosis, nephrolithiasis, or stage 3 CKD. Multivariable logistic regression was used to identify patient characteristics associated with parathyroidectomy. Data were analyzed from February 11, 2020, to October 8, 2020.Main Outcomes and Measures: The primary outcome was parathyroidectomy within 1 year of diagnosis.Results: Among 210 206 beneficiaries with an incident diagnosis of PHPT (78.8% women; mean [SD] age, 75.3 [6.8] years), 63 136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis. Among the subset of patients who met consensus guideline criteria for operative management (n=131 723), 38 983 (29.6%) were treated with parathyroidectomy. Patients treated operatively were younger (mean [SD] age, 73.5 [5.7] vs 76.0 [7.1] years) and more likely to be White (90.1% vs 86.0%), to be robust or prefrail (92.1% vs 85.7%), and to have fewer comorbidities (Charlson Comorbidity Index score of 0 or 1, 54.6% vs 44.1%), in addition to being more likely to live in socioeconomically disadvantaged (46.9% vs 40.3%) and rural (18.1% vs 13.6%) areas (all P<.001). On multivariable analysis, increasing age had a strong inverse association with parathyroidectomy among patients aged 76 to 85 years (unadjusted rate, 25.9%; odds ratio [OR], 0.68 [95% CI, 0.67-0.70]) and older than 85 years (unadjusted rate, 11.2%; OR, 0.27 [95% CI, 0.26-0.29]) compared with those aged 66 to 75 years (unadjusted rate, 35.6%), as did patients with moderate to severe frailty (unadjusted rate, 18.9%; OR, 0.60 [95% CI, 0.56-0.64]) compared with robust patients (unadjusted rate, 36.1%) and those with a Charlson Comorbidity Index score of 2 or greater (unadjusted rate, 25.9%; OR, 0.77 [95% CI, 0.75-0.79]) compared with a Charlson Comorbidity Index score of 0 (unadjusted rate, 37.0%). With regard to operative guidelines, a history of nephrolithiasis increased the odds of parathyroidectomy (OR, 1.43 [95% CI, 1.39-1.47]); stage 3 CKD decreased the odds of parathyroidectomy (OR, 0.71 [95% CI, 0.68-0.74]); and osteoporosis showed no association (OR, 1.01 [95% CI, 0.99-1.03]).Conclusions and Relevance: In this cohort study, most older adults with PHPT did not receive definitive treatment with parathyroidectomy. Older age, frailty, and multimorbidity were associated with nonoperative management, and guideline recommendations had minimal effect on treatment decisions. Further research is needed to identify barriers to surgical care and develop tools to target parathyroidectomy to older adults most likely to benefit.

  View details for DOI 10.1001/jamasurg.2020.6175

  View details for PubMedID 33404646

• Changes in brain functional connectivity and cognition related to white matter lesion burden in hypertensive patients from SPRINT. Neuroradiology Shah, C. n., Srinivasan, D. n., Erus, G. n., Schmitt, J. E., Agarwal, A. n., Cho, M. E., Lerner, A. J., Haley, W. E., Kurella Tamura, M. n., Davatzikos, C. n., Bryan, R. N., Fan, Y. n., Nasrallah, I. M. 2021

  Abstract

  Hypertension is a risk factor for cognitive impairment; however, the mechanisms leading to cognitive changes remain unclear. In this cross-sectional study, we evaluate the impact of white matter lesion (WML) burden on brain functional connectivity (FC) and cognition in a large cohort of hypertensive patients from the Systolic Blood Pressure Intervention Trial (SPRINT) at baseline.Functional networks were identified from baseline resting state functional MRI scans of 660 SPRINT participants using independent component analysis. WML volumes were calculated from structural MRI. Correlation analyses were carried out between mean FC of each functional network and global WML as well as WML within atlas-defined white matter regions. For networks of interest, voxel-wise-adjusted correlation analyses between FC and regional WML volume were performed. Multiple variable linear regression models were built for cognitive test performance as a function of network FC, followed by mediation analysis.Mean FC of the default mode network (DMN) was negatively correlated with global WML volume, and regional WML volume within the precuneus. Voxel-wise correlation analyses revealed that regional WML was negatively correlated with FC of the DMN's left lateral temporal region. FC in this region of the DMN was positively correlated to performance on the Montreal Cognitive Assessment and demonstrated significant mediation effects. Additional networks also demonstrated global and regional WML correlations; however, they did not demonstrate an association with cognition.In hypertensive patients, greater WML volume is associated with lower FC of the DMN, which in turn is related to poorer cognitive test performance.NCT01206062.

  View details for DOI 10.1007/s00234-020-02614-6

  View details for PubMedID 33404789

• Kidney Disease, Hypertension Treatment, and Cerebral Perfusion and Structure. American journal of kidney diseases : the official journal of the National Kidney Foundation Kurella Tamura, M., Gaussoin, S., Pajewski, N. M., Zaharchuk, G., Freedman, B. I., Rapp, S. R., Auchus, A. P., Haley, W. E., Oparil, S., Kendrick, J., Roumie, C. L., Beddhu, S., Cheung, A. K., Williamson, J. D., Detre, J. A., Dolui, S., Bryan, R. N., Nasrallah, I. M. 2021

  Abstract

  The safety of intensive blood pressure (BP) targets is controversial for persons with chronic kidney disease (CKD). We studied the effects of hypertension treatment on cerebral perfusion and structure in those with and without CKD.Neuroimaging substudy of a randomized trial.A subset of participants in the Systolic Blood Pressure Intervention Trial who underwent brain MRI studies. Presence of baseline CKD was assessed by estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR).Participants were randomly assigned to intensive (systolic BP <120 mm Hg) versus standard (systolic BP <140 mm Hg) BP lowering.The magnetic resonance imaging outcome measures were the four-year change in global cerebral blood flow, white matter lesion (WML) volume, and total brain volume.A total of 716 randomized participants with mean age of 68 years were enrolled; follow-up imaging occurred after a median 3.9 years. Among participants with eGFR <60 ml/min/1.73m2 (N=234), the effects of intensive versus standard BP treatment on change in global cerebral blood flow, WMLs and total brain volume were 3.38 mL/100 g/min (95% CI 0.32, 6.44), -0.06 cm3 (asinh transformed, 95% CI -0.16, 0.04), and -3.8 cm3 (95% CI -8.3, 0.7), respectively. Among participants with UACR >30 mg/g (N=151), the effects of intensive versus standard BP treatment on change in global cerebral blood flow, WMLs and total brain volume were 1.91 ml/100g/min (95% CI -3.01, 6.82), 0.003 cm3 (asinh transformed, 95% CI -0.13, 0.13), and -7.0 cm3 (95% CI -13.3, -0.3), respectively. The overall treatment effects on cerebral blood flow and total brain volume were not modified by baseline eGFR or UACR; however the effect on WMLs was attenuated in participants with albuminuria (interaction p-value 0.04).Measurement variability due to multi-site design.Among hypertensive adults with primarily early kidney disease, intensive versus standard blood pressure treatment did not appear to have a detrimental effect on brain perfusion or structure. The findings support the safety of intensive blood pressure treatment targets on brain health in persons with early kidney disease.

  View details for DOI 10.1053/j.ajkd.2021.07.024

  View details for PubMedID 34543687

• Measuring Patient Experience with Home Dialysis in the United States. Clinical journal of the American Society of Nephrology : CJASN Brady, B. M., Kurella Tamura, M. n. 2021

  View details for DOI 10.2215/CJN.01990221

  View details for PubMedID 33788703

• A Single Point-in-Time eGFR Is Not Associated with Increased Risk of Dementia in the Elderly Authors' Reply JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kurella Tamura, M., Pajewski, N., Weiner, D. E. 2020; 31 (12): 2966

  View details for DOI 10.1681/ASN.2020081189

  View details for Web of Science ID 000596028500019

• Authors' Reply. Journal of the American Society of Nephrology : JASN Kurella Tamura, M., Pajewski, N., Weiner, D. E. 2020; 31 (12): 2966

  View details for DOI 10.1681/ASN.2020081189

  View details for PubMedID 32931447

  View details for PubMedCentralID PMC7790209

• End-of-Life Care among US Adults with ESKD Who Were Waitlisted or Received a Kidney Transplant, 2005-2014 JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Butler, C. R., Reese, P. P., Perkins, J. D., Hall, Y. N., Curtis, J., Kurella Tamura, M., O'Hare, A. M. 2020; 31 (10): 2424-2433

  Abstract

  The care of patients in the United States who have ESKD is often shaped by their hopes and prognostic expectations related to kidney transplant. Little is known about how patients' engagement in the transplant process might relate to patterns of end-of-life care.We compared six measures of intensity of end-of-life care among adults in the United States with ESKD who died between 2005 and 2014 after experiencing differing exposure to the kidney transplant process.Of 567,832 decedents with ESKD, 27,633 (5%) had a functioning kidney transplant at the time of death, 14,653 (3%) had a failed transplant, 16,490 (3%) had been removed from the deceased donor waitlist, 17,010 (3%) were inactive on the waitlist, 11,529 (2%) were active on the waitlist, and 480,517 (85%) had never been waitlisted for or received a transplant (reference group). In adjusted analyses, compared with the reference group, patients exposed to the transplant process were significantly more likely to have been admitted to an intensive care unit and to have received an intensive procedure in the last 30 days of life; they were also significantly more likely to have died in the hospital. Those who died on the transplant waitlist were also less likely than those in the reference group to have been enrolled in hospice and to have discontinued dialysis before death.Patients who had engaged in the kidney transplant process received more intensive patterns of end-of-life care than other patients with ESKD. These findings support the relevance of advance care planning, even for this relatively healthy segment of the ESKD population.

  View details for DOI 10.1681/ASN.2020030342

  View details for Web of Science ID 000577091000020

  View details for PubMedID 32908000

  View details for PubMedCentralID PMC7608994

• Health-Related Quality of Life, Depressive Symptoms, and Kidney Transplant Access in Advanced CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. Kidney medicine Harhay, M. N., Yang, W., Sha, D., Roy, J., Chai, B., Fischer, M. J., Hamm, L. L., Hart, P. D., Hsu, C., Huan, Y., Huml, A. M., Kallem, R. R., Tamura, M. K., Porter, A. C., Ricardo, A. C., Slaven, A., Rosas, S. E., Townsend, R. R., Reese, P. P., Lash, J. P., Akkina, S., CRIC Study Investigators, Appel, L. J., Feldman, H. I., Go, A. S., He, J., Kusek, J. W., Rao, P., Rahman, M. 2020; 2 (5): 600

  Abstract

  Rationale & Objective: Among individuals with chronic kidney disease (CKD), poor self-reported health is associated with adverse outcomes including hospitalization and death. We sought to examine the association between health-related quality-of-life (HRQoL) and depressive symptoms in advanced CKD and subsequent access to the kidney transplant waiting list.Study Design: Prospective cohort study.Setting & Population: 1,676 Chronic Renal Insufficiency Cohort (CRIC) study participants with estimated glomerular filtration rates≤30mL/min/1.73m2 at study entry or during follow-up.Exposures: HRQoL ascertained by 5 scales of the Kidney Disease Quality of Life-36 Survey (Physical Component Summary [PCS], Mental Component Summary, Symptoms, Burdens, and Effects), with higher scores indicating better HRQoL, and depressive symptoms ascertained using the Beck Depression Inventory.Outcomes: Time to kidney transplant wait-listing and time to pre-emptive wait-listing.Analytic Approach: Time-to-event analysis using Cox proportional hazards regression.Results: During a median follow-up of 5.1 years, 652 (39%) participants were wait-listed, of whom 304 were preemptively wait-listed. Adjusted for demographics, comorbid conditions, estimated glomerular filtration rate slope, and cognitive function, participants with the highest scores on the Burden and Effects scales, respectively, had lower rates of wait-listing than those with the lowest scores on the Burden (wait-listing adjusted hazard ratio [aHR], 0.70; 95% CI, 0.57-0.85; P<0.001) and Effects scales (wait-listing aHR, 0.74; 95% CI, 0.59-0.92; P=0.007). Participants with fewer depressive symptoms (ie, Beck Depression Inventory score<14) had lower wait-listing rates than those with more depressive symptoms (aHR, 0.81; 95% CI, 0.66-0.99; P=0.04). Participants with lower Burden and Effects scale scores and those with higher Symptoms and PCS scores had higher pre-emptive wait-listing rates (aHR in highest tertile of PCS relative to lowest tertile, 1.58; 95% CI, 1.12-2.23; P= 0.01).Limitations: Unmeasured confounders.Conclusions: Self-reported health in late-stage CKD may influence the timing of kidney transplantation.

  View details for DOI 10.1016/j.xkme.2020.06.010

  View details for PubMedID 33089138

• Cardiopulmonary Resuscitation Preferences of People Receiving Dialysis JAMA NETWORK OPEN Bernacki, G. M., Engelberg, R. A., Curtis, J., Tamura, M., Brumback, L. C., Lavallee, D. C., Vig, E. K., O'Hare, A. M. 2020; 3 (8): e2010398

  Abstract

  Whether the cardiopulmonary resuscitation (CPR) preferences of patients receiving dialysis align with their values and other aspects of end-of-life care is not known.To describe the CPR preferences of patients receiving dialysis and how these preferences are associated with their responses to questions about other aspects of end-of-life care.Cross-sectional survey study of a consecutive sample of patients receiving dialysis at 31 nonprofit dialysis facilities in 2 US metropolitan areas (Seattle, Washington, and Nashville, Tennessee) between April 22, 2015, and October 2, 2018. Analyses for this article were conducted between December 2018 and April 2020.Participants were asked to respond to the question "If you had to decide right now, would you want CPR if your heart were to stop beating?" Those who indicated they would probably or definitely want CPR were categorized as preferring CPR.This study examined the association between preference for CPR and other treatment preferences, engagement in advance care planning, values, desired place of death, expectations about prognosis, symptoms, and palliative care needs.Of the 1434 individuals invited to complete the survey, 1009 agreed to participate, and 876 were included in the analytic cohort (61.1%). The final cohort had a mean (SD) age of 62.6 (14.0) years; 492 (56.2%) were men, and 528 (60.3%) were White individuals. Among 738 of 876 participants (84.2%) who indicated that they would definitely or probably want CPR (CPR group), 555 (75.2%) wanted mechanical ventilation vs 13 of 138 (9.4%) of those who did not want CPR (do not resuscitate [DNR] group) (P < .001). A total of 249 of 738 participants (33.7%) in the CPR group vs 84 of 138 (60.9%) in the DNR group had documented treatment preferences (P < .001). In terms of values about future care, 171 participants (23.2%) in the CPR group vs 5 of 138 (3.6%) in the DNR group valued life prolongation (P < .001); 320 in the CPR group (43.4%) vs 109 of 138 in the DNR group (79.0%) valued comfort (P < .001); and 247 participants (33.5%) in the CPR group vs 24 of 138 (17.4%) in the DNR group were unsure about their wishes for future care (P < .001). In the CPR group, 207 (28.0%) had thought about stopping dialysis vs 62 of 138 (44.9%) in the DNR group (P < .001), and 181 (24.5%) vs 58 of 138 (42.0%) had discussed stopping dialysis (P = .001). No statistically significant associations were observed between CPR preference and documentation of a surrogate decision maker, thoughts or discussion of hospice, preferred place of death, expectations about prognosis, reported symptoms, or palliative care needs.The CPR preferences of patients receiving dialysis were associated with some, but not all, other aspects of end-of-life care. How participants responded to questions about these other aspects of end-of-life care were not always aligned with their CPR preference. More work is needed to integrate discussions about code status with bigger picture conversations about patients' values, goals, and preferences for end-of-life care.

  View details for DOI 10.1001/jamanetworkopen.2020.10398

  View details for Web of Science ID 000567336400001

  View details for PubMedID 32833017

  View details for PubMedCentralID PMC7445594

• Analysis of Primary Hyperparathyroidism Screening Among US Veterans With Kidney Stones. JAMA surgery Ganesan, C., Weia, B., Thomas, I., Song, S., Velaer, K., Seib, C. D., Conti, S., Elliott, C., Chertow, G. M., Kurella Tamura, M., Leppert, J. T., Pao, A. C. 2020

  Abstract

  Importance: Approximately 3% to 5% of patients with kidney stones have primary hyperparathyroidism (PHPT), a treatable cause of recurrent stones. However, the rate of screening for PHPT in patients with kidney stones remains unknown.Objectives: To estimate the prevalence of parathyroid hormone (PTH) testing in veterans with kidney stones and hypercalcemia and to identify the demographic, geographic, and clinical characteristics of veterans who were more or less likely to receive PTH testing.Design, Setting, and Participants: This cohort study obtained Veterans Health Administration (VHA) health records from the Corporate Data Warehouse for veterans who received care in 1 of the 130 VHA facilities across the United States from January 1, 2008, through December 31, 2013. Historical encounters, medical codes, and laboratory data were assessed. Included patients had diagnostic or procedural codes for kidney or ureteral stones, and excluded patients were those with a previous serum PTH level measurement. Data were collected from January 1, 2006, to December 31, 2014. Data analysis was conducted from June 1, 2019, to January 31, 2020.Exposures: Elevated serum calcium concentration measurement between 6 months before and 6 months after kidney stone diagnosis.Main Outcomes and Measures: Proportion of patients with a serum PTH level measurement and proportion of patients with biochemical evidence of PHPT who underwent parathyroidectomy.Results: The final cohort comprised 7561 patients with kidney stones and hypercalcemia and a mean (SD) age of 64.3 (12.3) years. Of these patients, 7139 were men (94.4%) and 5673 were white individuals (75.0%). The proportion of patients who completed a serum PTH level measurement was 24.8% (1873 of 7561). Across the 130 VHA facilities included in the study, testing rates ranged from 4% to 57%. The factors associated with PTH testing included the magnitude of calcium concentration elevation (odds ratio [OR], 1.07 per 0.1 mg/dL >10.5 mg/dL; 95% CI, 1.05-1.08) and the number of elevated serum calcium concentration measurements (OR, 1.08 per measurement >10.5 mg/dL; 95% CI, 1.06-1.10) as well as visits to both a nephrologist and a urologist (OR, 6.57; 95% CI, 5.33-8.10) or an endocrinologist (OR, 4.93; 95% CI, 4.11-5.93). Of the 717 patients with biochemical evidence of PHPT, 189 (26.4%) underwent parathyroidectomy within 2 years of a stone diagnosis.Conclusions and Relevance: This cohort study found that only 1 in 4 patients with kidney stones and hypercalcemia were tested for PHPT in VHA facilities and that testing rates varied widely across these facilities. These findings suggest that raising clinician awareness to PHPT screening indications may improve evaluation for parathyroidectomy, increase the rates of detection and treatment of PHPT, and decrease recurrent kidney stone disease.

  View details for DOI 10.1001/jamasurg.2020.2423

  View details for PubMedID 32725208

• Association of 24-Hour Ambulatory Blood Pressure Patterns with Cognitive Function and Physical Functioning in CKD. Clinical journal of the American Society of Nephrology : CJASN Ghazi, L. n., Yaffe, K. n., Tamura, M. K., Rahman, M. n., Hsu, C. Y., Anderson, A. H., Cohen, J. B., Fischer, M. J., Miller, E. R., Navaneethan, S. D., He, J. n., Weir, M. R., Townsend, R. R., Cohen, D. L., Feldman, H. I., Drawz, P. E. 2020

  Abstract

  Hypertension is highly prevalent in patients with CKD as is cognitive impairment and frailty, but the link between them is understudied. Our objective was to determine the association between ambulatory BP patterns, cognitive function, physical function, and frailty among patients with nondialysis-dependent CKD.Ambulatory BP readings were obtained on 1502 participants of the Chronic Renal Insufficiency Cohort. We evaluated the following exposures: (1) BP patterns (white coat, masked, sustained versus controlled hypertension) and (2) dipping patterns (reverse, extreme, nondippers versus normal dippers). Outcomes included the following: (1) cognitive impairment scores from the Modified Mini Mental Status Examination of <85, <80, and <75 for participants <65, 65-79, and ≥80 years, respectively; (2) physical function, measured by the short physical performance battery (SPPB), with higher scores (0-12) indicating better functioning; and (3) frailty, measured by meeting three or more of the following criteria: slow gait speed, muscle weakness, low physical activity, exhaustion, and unintentional weight loss. Cognitive function and frailty were assessed at the time of ambulatory BP (baseline) and annually thereafter. SPPB was assessed at baseline logistic and linear regression and Cox discrete models assessed the cross-sectional and longitudinal relationship between dipping and BP patterns and outcomes.Mean age of participants was 63±10 years, 56% were male, and 39% were black. At baseline, 129 participants had cognitive impairment, and 275 were frail. Median SPPB score was 9 (interquartile range, 7-10). At baseline, participants with masked hypertension had 0.41 (95% CI, -0.78 to -0.05) lower SPPB scores compared with those with controlled hypertension in the fully adjusted model. Over 4 years of follow-up, 529 participants had incident frailty, and 207 had incident cognitive impairment. After multivariable adjustment, there was no association between BP or dipping patterns and incident frailty or cognitive impairment.In patients with CKD, dipping and BP patterns are not associated with incident or prevalent cognitive impairment or prevalent frailty.

  View details for DOI 10.2215/CJN.10570919

  View details for PubMedID 32217634

• Racial and Sex Disparities in Catheter Use and Dialysis Access in the United States Medicare Population. Journal of the American Society of Nephrology : JASN Arya, S. n., Melanson, T. A., George, E. L., Rothenberg, K. A., Kurella Tamura, M. n., Patzer, R. E., Hockenberry, J. M. 2020

  Abstract

  Despite efforts to increase arteriovenous fistula and graft use, 80% of patients in the United States start hemodialysis on a central venous catheter (CVC).To better understand in incident hemodialysis patients how sex and race/ethnicity are associated with time on a central venous catheter and transition to an arteriovenous fistula and graft, our observational cohort study analyzed US Renal Data System data for patients with incident ESKD aged ≥66 years who started hemodialysis on a CVC in July 2010 through 2013.At 1 year, 32.7% of 74,194 patients transitioned to an arteriovenous fistula, 10.8% transitioned to an arteriovenous graft, 32.1% stayed on a CVC, and 24.5% died. Women spent a significantly longer time on a CVC than men. Compared with white patients, patients who were black, Hispanic, or of another racial/ethnicity minority spent significantly more days on a CVC. In competing risk regression, women were significantly less likely than men to transition to a fistula and more likely to transition to a graft. Compared with white patients, blacks were significantly less likely to transition to a fistula but more likely to transition to a graft, Hispanics were significantly more likely to transition to a fistula, and other races/ethnicities were significantly more likely to transition to either a fistula or a graft.Female patients spend a longer time on a CVC and are less likely to transition to permanent access. Compared with white patients, minorities also spend longer time on a CVC, but are more likely to eventually transition to permanent access. Strategies to speed transition to permanent access should target groups that currently lag in this area.

  View details for DOI 10.1681/ASN.2019030274

  View details for PubMedID 31941721

• Medical Record Documentation of Goals-of-Care Discussions Among Older Veterans With Incident Kidney Failure. American journal of kidney diseases : the official journal of the National Kidney Foundation Bradshaw, C. L., Gale, R. C., Chettiar, A., Ghaus, S. J., Thomas, I., Fung, E., Lorenz, K., Asch, S. M., Anand, S., Kurella Tamura, M. 2019

  Abstract

  RATIONALE & OBJECTIVE: Elicitation and documentation of patient preferences is at the core of shared decision making and is particularly important among patients with high anticipated mortality. The extent to which older patients with incident kidney failure undertake such discussions with their providers is unknown and its characterization was the focus of this study.STUDY DESIGN: Retrospective cohort study.SETTING & PARTICIPANTS: A random sample of veterans 67 years and older with incident kidney failure receiving care from the US Veterans Health Administration between 2005 and2010.EXPOSURES: Demographic and facility characteristics, as well as predicted 6-month mortality risk after dialysis initiation and documentation of resuscitation preferences.OUTCOMES: Documented discussions of dialysis treatment and supportive care.ANALYTICAL APPROACH: We reviewed medical records over the 2 years before incident kidney failure and up to 1 year afterward to ascertain the frequency and timing of documented discussions about dialysis treatment, supportive care, and resuscitation. Logistic regression was used to identify factors associated with these documented discussions.RESULTS: The cohort of 821 veterans had a mean age of 80.9±7.2 years, and 37.2% had a predicted 6-month mortality risk>20% with dialysis. Documented discussions addressing dialysis treatment and resuscitation were present in 55.6% and 77.1% of patients, respectively. Those addressing supportive care were present in 32.4%. The frequency of documentation varied by mortality risk and whether the patient ultimately started dialysis. In adjusted analyses, the frequency and pattern of documentation were more strongly associated with geographic location and receipt of outpatient nephrology care than with patient demographic or clinical characteristics.LIMITATIONS: Documentation may not fully reflect the quality and content of discussions, and generalizability to nonveteran patients is limited.CONCLUSIONS: Among older veterans with incident kidney failure, discussions of dialysis treatment are decoupled from other aspects of advance care planning and are suboptimally documented, even among patients at high risk for mortality.

  View details for DOI 10.1053/j.ajkd.2019.07.024

  View details for PubMedID 31679746

• Assessment of Self-reported Prognostic Expectations of People Undergoing Dialysis: United States Renal Data System Study of Treatment Preferences (USTATE). JAMA internal medicine O'Hare, A. M., Kurella Tamura, M., Lavallee, D. C., Vig, E. K., Taylor, J. S., Hall, Y. N., Katz, R., Curtis, J. R., Engelberg, R. A. 2019

  Abstract

  Importance: Prognostic understanding can shape patients' treatment goals and preferences. Patients undergoing dialysis in the United States have limited life expectancy and may receive end-of-life care directed at life extension. Little is known about their prognostic expectations.Objective: To understand the prognostic expectations of patients undergoing dialysis and how these relate to care planning, goals, and preferences.Design, Setting, and Participants: Cross-sectional survey study of 996 eligible patients treated with regular dialysis at 31 nonprofit dialysis facilities in 2 metropolitan areas (Seattle, Washington, and Nashville, Tennessee) between April 2015 and October 2018. After a pilot phase, 1434 eligible patients were invited to participate (response rate, 69.5%). To provide a context for interpreting survey participants' prognostic estimates, United States Renal Data System standard analysis files were used to construct a comparison cohort of 307 602 patients undergoing in-center hemodialysis on January 1, 2006, and followed for death through July 31, 2017. Final analyses for this study were conducted between November 2018 and March 2019.Exposures: Responses to the question "How long would you guess people your age with similar health conditions usually live?" (<5 years, 5-10 years, >10 years, or not sure).Main Outcomes and Measures: Self-reported (1) documentation of a surrogate decision-maker, (2) documentation of treatment preferences, (3) values around life prolongation, (4) preferences for receipt of cardiopulmonary resuscitation and mechanical ventilation, and (5) desired place of death.Results: Of the 996 survey respondents, the mean (SD) age was 62.7 (13.9) years, and 438 (44.0%) were women. Overall, 112 (11.2%) survey respondents selected a prognosis of fewer than 5 years, 150 (15.1%) respondents selected 5 to 10 years, 330 (33.1%) respondents selected more than 10 years, and 404 (40.6%) were not sure. By comparison, 185 427 (60.3%) prevalent US in-center patients undergoing hemodialysis died within 5 years, 58 437 (19.0%) died within 5 to 10 years, and 63 738 (20.7%) lived more than 10 years. In analyses adjusted for participant characteristics, survey respondents with a prognostic expectation of more than 10 years (vs <5 years) were less likely to report documentation of a surrogate decision-maker (adjusted odds ratio [aOR], 0.6; 95% CI, 0.4-0.9) and treatment preferences (aOR, 0.4; 95% CI, 0.2-0.6) and to value comfort over life extension (aOR, 0.1; 95% CI, 0.04-0.3), and were more likely to want cardiopulmonary resuscitation (aOR, 5.3; 95% CI, 3.2-8.7) and mechanical ventilation (aOR, 2.2; 95% CI, 1.2-3.7). The respondents who reported that they were not sure about prognosis had similar associations.Conclusions and Relevance: Uncertain and overly optimistic prognostic expectations may limit the benefit of advance care planning and contribute to high-intensity end-of-life care in patients undergoing dialysis.

  View details for DOI 10.1001/jamainternmed.2019.2879

  View details for PubMedID 31282920

• Paying for Hemodialysis in Kerala, India: A Description of Household Financial Hardship in the Context of Medical Subsidy KIDNEY INTERNATIONAL REPORTS Bradshaw, C., Gracious, N., Narayanan, R., Narayanan, S., Safeer, M., Nair, G. M., Murlidharan, P., Sundaresan, A., Santhi, S., Prabhakaran, D., Tamura, M., Jha, V., Chertow, G. M., Jeemon, P., Anand, S. 2019; 4 (3): 390–98

  View details for DOI 10.1016/j.ekir.2018.12.007

  View details for Web of Science ID 000460067100007

• Paying for Hemodialysis in Kerala, India: A Description of Household Financial Hardship in the Context of Medical Subsidy. Kidney international reports Bradshaw, C., Gracious, N., Narayanan, R., Narayanan, S., Safeer, M., Nair, G. M., Murlidharan, P., Sundaresan, A., Retnaraj Santhi, S., Prabhakaran, D., Kurella Tamura, M., Jha, V., Chertow, G. M., Jeemon, P., Anand, S. 2019; 4 (3): 390-398

  Abstract

  Many low- and middle-income countries are implementing strategies to increase dialysis availability as growing numbers of people reach end-stage renal disease. Despite efforts to subsidize care, the economic sustainability of chronic dialysis in these settings remains uncertain. We evaluated the association of medical subsidy with household financial hardship related to hemodialysis in Kerala, India, a state with high penetrance of procedure-based subsidies for patients on dialysis.Patients on maintenance hemodialysis at 15 facilities in Kerala were administered a questionnaire that ascertained demographics, dialysis details, and household finances. We estimated direct and indirect costs of hemodialysis, and described the use of medical subsidy. We evaluated whether presence of subsidy (private, charity, or government-sponsored) was associated with lower catastrophic health expenditure (defined as ≥40% of nonsubsistence expenditure spent on dialysis) or distress financing.Of the 835 patients surveyed, 759 (91%) reported their households experienced catastrophic health expenditure, and 644 (77%) engaged in distress financing. Median dialysis-related expenditure was 80% (25th-75th percentile: 60%-90%) of household nonsubsistence expenditure. Government subsidies were used by 238 (29%) of households, 139 (58%) of which were in the lowest income category. Catastrophic health expenditure was present in 215 (90%) of households receiving government subsidy and 332 (93%) without subsidy.Provision of medical subsidy in Kerala, India was not associated with lower rates of household financial hardship related to long-term hemodialysis therapy. Transparent counseling on impending costs and innovative strategies to mitigate household financial distress are necessary for persons with end-stage renal disease in resource-limited settings.

  View details for DOI 10.1016/j.ekir.2018.12.007

  View details for PubMedID 30899866

  View details for PubMedCentralID PMC6409432

• Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia A Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Williamson, J. D., Pajewski, N. M., Auchus, A. P., Bryan, R., Chelune, G., Cheung, A. K., Cleveland, M. L., Coker, L. H., Crowe, M. G., Cushman, W. C., Cutler, J. A., Davatzikos, C., Desiderio, L., Erus, G., Fine, L. J., Gaussoin, S. A., Harris, D., Hsieh, M., Johnson, K. C., Kimmel, P. L., Tamura, M., Launer, L. J., Lerner, A. J., Lewis, C. E., Martindale-Adams, J., Moy, C. S., Nasrallah, I. M., Nichols, L. O., Oparil, S., Ogrocki, P. K., Rahman, M., Rapp, S. R., Reboussin, D. M., Rocco, M. V., Sachs, B. C., Sink, K. M., Still, C. H., Supiano, M. A., Snyder, J. K., Wadley, V. G., Walker, J., Weiner, D. E., Whelton, P. K., Wilson, V. M., Woolard, N., Wright, J. T., Wright, C. B., SPRINT MIND Investigators SPRINT 2019; 321 (6): 553–61

  View details for DOI 10.1001/jama.2018.21442

  View details for Web of Science ID 000458456700016

• Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial. JAMA SPRINT MIND Investigators for the SPRINT Research Group, Williamson, J. D., Pajewski, N. M., Auchus, A. P., Bryan, R. N., Chelune, G., Cheung, A. K., Cleveland, M. L., Coker, L. H., Crowe, M. G., Cushman, W. C., Cutler, J. A., Davatzikos, C., Desiderio, L., Erus, G., Fine, L. J., Gaussoin, S. A., Harris, D., Hsieh, M., Johnson, K. C., Kimmel, P. L., Tamura, M. K., Launer, L. J., Lerner, A. J., Lewis, C. E., Martindale-Adams, J., Moy, C. S., Nasrallah, I. M., Nichols, L. O., Oparil, S., Ogrocki, P. K., Rahman, M., Rapp, S. R., Reboussin, D. M., Rocco, M. V., Sachs, B. C., Sink, K. M., Still, C. H., Supiano, M. A., Snyder, J. K., Wadley, V. G., Walker, J., Weiner, D. E., Whelton, P. K., Wilson, V. M., Woolard, N., Wright, J. T., Wright, C. B. 2019

  Abstract

  Importance: There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia.Objective: To evaluate the effect of intensive blood pressure control on risk of dementia.Design, Setting, and Participants: Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018.Interventions: Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n=4678) or less than 140 mm Hg (standard treatment group; n=4683).Main Outcomes and Measures: The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia.Results: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97).Conclusions and Relevance: Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point.Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

  View details for PubMedID 30688979

• Prevalence of twenty-four hour urine testing in Veterans with urinary stone disease. PloS one Ganesan, C. n., Thomas, I. C., Song, S. n., Sun, A. J., Sohlberg, E. M., Kurella Tamura, M. n., Chertow, G. M., Liao, J. C., Conti, S. n., Elliott, C. S., Leppert, J. T., Pao, A. C. 2019; 14 (8): e0220768

  Abstract

  The American Urological Association guidelines recommend 24-hour urine testing in patients with urinary stone disease to decrease the risk of stone recurrence; however, national practice patterns for 24-hour urine testing are not well characterized. Our objective is to determine the prevalence of 24-hour urine testing in patients with urinary stone disease in the Veterans Health Administration and examine patient-specific and facility-level factors associated with 24-hour urine testing. Identifying variations in clinical practice can inform future quality improvement efforts in the management of urinary stone disease in integrated healthcare systems.We accessed national Veterans Health Administration data through the Corporate Data Warehouse (CDW), hosted by the Veterans Affairs Informatics and Computing Infrastructure (VINCI), to identify patients with urinary stone disease. We defined stone formers as Veterans with one inpatient ICD-9 code for kidney or ureteral stones, two or more outpatient ICD-9 codes for kidney or ureteral stones, or one or more CPT codes for kidney or ureteral stone procedures from 2007 through 2013. We defined a 24-hour urine test as a 24-hour collection for calcium, oxalate, citrate or sulfate. We used multivariable regression to assess demographic, geographic, and selected clinical factors associated with 24-hour urine testing.We identified 130,489 Veterans with urinary stone disease; 19,288 (14.8%) underwent 24-hour urine testing. Patients who completed 24-hour urine testing were younger, had fewer comorbidities, and were more likely to be White. Utilization of 24-hour urine testing varied widely by geography and facility, the latter ranging from 1 to 40%.Fewer than one in six patients with urinary stone disease complete 24-hour urine testing in the Veterans Health Administration. In addition, utilization of 24-hour urine testing varies widely by facility identifying a target area for improvement in the care of patients with urinary stone disease. Future efforts to increase utilization of 24-hour urine testing and improve clinician awareness of targeted approaches to stone prevention may be warranted to reduce the morbidity and cost of urinary stone disease.

  View details for DOI 10.1371/journal.pone.0220768

  View details for PubMedID 31393935

• Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions. JAMA SPRINT MIND Investigators for the SPRINT Research Group, Nasrallah, I. M., Pajewski, N. M., Auchus, A. P., Chelune, G., Cheung, A. K., Cleveland, M. L., Coker, L. H., Crowe, M. G., Cushman, W. C., Cutler, J. A., Davatzikos, C., Desiderio, L., Doshi, J., Erus, G., Fine, L. J., Gaussoin, S. A., Harris, D., Johnson, K. C., Kimmel, P. L., Kurella Tamura, M., Launer, L. J., Lerner, A. J., Lewis, C. E., Martindale-Adams, J., Moy, C. S., Nichols, L. O., Oparil, S., Ogrocki, P. K., Rahman, M., Rapp, S. R., Reboussin, D. M., Rocco, M. V., Sachs, B. C., Sink, K. M., Still, C. H., Supiano, M. A., Snyder, J. K., Wadley, V. G., Walker, J., Weiner, D. E., Whelton, P. K., Wilson, V. M., Woolard, N., Wright, J. T., Wright, C. B., Williamson, J. D., Bryan, R. N. 2019; 322 (6): 524–34

  Abstract

  Importance: The effect of intensive blood pressure lowering on brain health remains uncertain.Objective: To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes.Design, Setting, and Participants: A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n=670) and at 4 years of follow-up (n=449); final follow-up date was July 1, 2016.Interventions: Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n=355) or less than 140 mm Hg (standard treatment, n=315).Main Outcomes and Measures: The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome.Results: Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3 (difference, 0.92 cm3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3 (difference, 1.45 cm3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, -0.54 cm3 [95% CI, -0.87 to -0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3 (difference, -30.6 cm3 [95% CI, -32.3 to -28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3 (difference, -26.9 cm3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, -3.7 cm3 [95% CI, -6.3 to -1.1]).Conclusions and Relevance: Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small.Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

  View details for DOI 10.1001/jama.2019.10551

  View details for PubMedID 31408137

• Cognitive Impairment in Non-Dialysis-Dependent CKD and the Transition to Dialysis: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study AMERICAN JOURNAL OF KIDNEY DISEASES Harhay, M. N., Xie, D., Zhang, X., Hsu, C., Vittinghoff, E., Go, A. S., Sozio, S. M., Blumenthal, J., Seliger, S., Chen, J., Deo, R., Dobre, M., Akkina, S., Reese, P. P., Lash, J. P., Yaffe, K., Tamura, M., CRIC Study Investigators 2018; 72 (4): 499–508

  Abstract

  Advanced chronic kidney disease is associated with elevated risk for cognitive impairment. However, it is not known whether and how cognitive impairment is associated with planning and preparation for end-stage renal disease.Retrospective observational study.630 adults participating in the CRIC (Chronic Renal Insufficiency Cohort) Study who had cognitive assessments in late-stage CKD, defined as estimated glome-rular filtration rate ≤ 20mL/min/1.73m2, and subsequently initiated maintenance dialysis therapy.Predialysis cognitive impairment, defined as a score on the Modified Mini-Mental State Examination lower than previously derived age-based threshold scores. Covariates included age, race/ethnicity, educational attainment, comorbid conditions, and health literacy.Peritoneal dialysis (PD) as first dialysis modality, preemptive permanent access placement, venous catheter avoidance at dialysis therapy initiation, and preemptive wait-listing for a kidney transplant.Multivariable-adjusted logistic regression.Predialysis cognitive impairment was present in 117 (19%) participants. PD was the first dialysis modality among 16% of participants (n=100), 75% had preemptive access placed (n=473), 45% avoided using a venous catheter at dialysis therapy initiation (n=279), and 20% were preemptively wait-listed (n=126). Predialysis cognitive impairment was independently associated with 78% lower odds of PD as the first dialysis modality (adjusted OR [aOR], 0.22; 95% CI, 0.06-0.74; P=0.02) and 42% lower odds of venous catheter avoidance at dialysis therapy initiation (aOR, 0.58; 95% CI, 0.34-0.98; P=0.04). Predialysis cognitive impairment was not independently associated with preemptive permanent access placement or wait-listing.Potential unmeasured confounders; single measure of cognitive function.Predialysis cognitive impairment is associated with a lower likelihood of PD as a first dialysis modality and of venous catheter avoidance at dialysis therapy initiation. Future studies may consider addressing cognitive function when testing strategies to improve patient transitions to dialysis therapy.

  View details for PubMedID 29728316

  View details for PubMedCentralID PMC6153064

• Association of Inpatient Palliative Care with Health Care Utilization and Postdischarge Outcomes among Medicare Beneficiaries with End Stage Kidney Disease CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chettiar, A., Montez-Rath, M., Liu, S., Hall, Y. N., O'Hare, A. M., Kurella Tamura, M. 2018; 13 (8): 1180–87

  Abstract

  Palliative care may improve quality of life and reduce the cost of care for patients with chronic illness, but utilization and cost implications of palliative care in ESKD have not been evaluated. We sought to determine the association of inpatient palliative care with health care utilization and postdischarge outcomes in ESKD.In analyses stratified by whether patients died during the index hospitalization, we identified Medicare beneficiaries with ESKD who received inpatient palliative care, ascertained by provider specialty codes, between 2012 and 2013. These patients were matched to hospitalized patients who received usual care using propensity scores. Primary outcomes were length of stay and hospitalization costs. Secondary outcomes were 30-day readmission and hospice enrollment.Inpatient palliative care occurred in <1% of hospitalizations lasting >2 days. Among the decedent cohort (n=1308), inpatient palliative care was associated with a 21% shorter length of stay (-4.2 days; 95% confidence interval, -5.6 to -2.9 days) and 14% lower hospitalization costs (-$10,698; 95% confidence interval, -$17,553 to -$3843) compared with usual care. Among the nondecedent cohort (n=5024), inpatient palliative care was associated with no difference in length of stay (0.4 days; 95% confidence interval, -0.3 to 1.0 days) and 11% higher hospitalization costs ($4275; 95% confidence interval, $1984 to $6567) compared with usual care. In the 30-day postdischarge period, patients who received inpatient palliative care had higher likelihood of hospice enrollment (hazard ratio, 8.3; 95% confidence interval, 6.6 to 10.5) and lower likelihood of rehospitalization (hazard ratio, 0.8; 95% confidence interval, 0.7 to 0.9).Among patients with ESKD who died in the hospital, inpatient palliative care was associated with shorter hospitalizations and lower costs. Among those who survived to discharge, inpatient palliative care was associated with no difference in length of stay and higher hospitalization costs but markedly higher hospice use and fewer readmissions after discharge.

  View details for PubMedID 30026286

  View details for PubMedCentralID PMC6086714

• Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M., Desai, M., Kapphahn, K. I., Thomas, I., Asch, S. M., Chertow, G. M. 2018; 29 (8): 2169–77

  View details for DOI 10.1681/ASN.2017121273

  View details for Web of Science ID 000445764500017

• Association Between Hospice Length of Stay, Health Care Utilization, and Medicare Costs at the End of Life Among Patients Who Received Maintenance Hemodialysis JAMA INTERNAL MEDICINE Wachterman, M. W., Hailpern, S. M., Keating, N. L., Tamura, M., O'Hare, A. M. 2018; 178 (6): 792–99

  Abstract

  Patients with end-stage renal disease are less likely to use hospice services than other patients with advanced chronic illness. Little is known about the timing of hospice referral in this population and its association with health care utilization and costs.To examine the association between hospice length of stay and health care utilization and costs at the end of life among Medicare beneficiaries who had received maintenance hemodialysis.This cross-sectional observational study was conducted via the United States Renal Data System registry. Participants were all 770 191 hemodialysis patients in the registry who were enrolled in fee-for-service Medicare and died between January 1, 2000, and December 31, 2014. The dates of analysis were April 2016 to December 2017.Hospital admission, intensive care unit (ICU) admission, and receipt of an intensive procedure during the last month of life; death in the hospital; and costs to the Medicare program in the last week of life.Among 770 191 patients, the mean (SD) age was 74.8 (11.0) years, and 53.7% were male. Twenty percent of cohort members were receiving hospice services when they died. Of these, 41.5% received hospice for 3 days or fewer. In adjusted analyses, compared with patients who did not receive hospice, those enrolled in hospice for 3 days or fewer were less likely to die in the hospital (13.5% vs 55.1%; P < .001) or to undergo an intensive procedure in the last month of life (17.7% vs 31.6%; P < .001) but had higher rates of hospitalization (83.6% vs 74.4%; P < .001) and ICU admission (54.0% vs 51.0%; P < .001) and similar Medicare costs in the last week of life ($10 756 vs $10 871; P = .08). Longer lengths of stay in hospice beyond 3 days were associated with progressively lower rates of utilization and costs, especially for those referred more than 15 days before death (35.1% hospitalized and 16.7% admitted to an ICU in the last month of life; the mean Medicare costs in the last week of life were $3221).Overall, 41.5% of hospice enrollees who had been treated with hemodialysis for their end-stage renal disease entered hospice within 3 days of death. Although less likely to die in the hospital and to receive an intensive procedure, these patients were more likely than those not enrolled in hospice to be hospitalized and admitted to the ICU, and they had similar Medicare costs. Without addressing barriers to more timely referral, greater use of hospice may not translate into meaningful changes in patterns of health care utilization, costs, and quality of care at the end of life in this population.

  View details for DOI 10.1001/jamainternmed.2018.0256

  View details for Web of Science ID 000434133500016

  View details for PubMedID 29710217

  View details for PubMedCentralID PMC5988968

• Hospice Use And End-Of-Life Spending Trajectories In Medicare Beneficiaries On Hemodialysis HEALTH AFFAIRS O'Hare, A. M., Hailpern, S. M., Wachterman, M., Kreuter, W., Katz, R., Hall, Y. N., Montez-Rath, M., Tamura, M., Daratha, K. B. 2018; 37 (6): 980–87

  View details for DOI 10.1377/hlthaff.2017.1181

  View details for Web of Science ID 000463956300020

• Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4+): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference KIDNEY INTERNATIONAL Eckardt, K., Bansal, N., Coresh, J., Evans, M., Grams, M. E., Herzog, C. A., James, M. T., Heerspink, H. L., Pollock, C. A., Stevens, P. E., Tamura, M., Tonelli, M. A., Wheeler, D. C., Winkelmayer, W. C., Cheung, M., Hemmelgarn, B. R., Conference Participants 2018; 93 (6): 1281–92

  Abstract

  Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences.

  View details for PubMedID 29656903

• Palliative Care Disincentives in CKD: Changing Policy to Improve CKD Care AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M., O'Hare, A. M., Lin, E., Holdsworth, L. M., Malcolm, E., Moss, A. H. 2018; 71 (6): 866–73

  Abstract

  The dominant health delivery model for advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States, which focuses on provision of dialysis, is ill-equipped to address many of the needs of seriously ill patients. Although palliative care may address some of these gaps in care, its integration into advanced CKD care has been suboptimal due to several health system barriers. These barriers include uneven access to specialty palliative care services, underdeveloped models of care for seriously ill patients with advanced CKD, and misaligned policy incentives. This article reviews policies that affect the delivery of palliative care for this population, discusses reforms that could address disincentives to palliative care, identifies quality measurement issues for palliative care for individuals with advanced CKD and ESRD, and considers potential pitfalls in the implementation of new models of integrated palliative care. Reforming health care delivery in ways that remove policy disincentives to palliative care for patients with advanced CKD and ESRD will fill a critical gap in care.

  View details for PubMedID 29510920

  View details for PubMedCentralID PMC5970958

• Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD. Journal of the American Society of Nephrology : JASN Kurella Tamura, M., Desai, M., Kapphahn, K. I., Thomas, I., Asch, S. M., Chertow, G. M. 2018

  Abstract

  Background Appropriate patient selection and optimal timing of dialysis initiation among older adults with advanced CKD are uncertain. We determined the association between dialysis versus medical management and survival at different ages and levels of kidney function.Methods We assembled a nationally representative 20% sample of United States veterans with eGFR<30 ml/min per 1.73 m2 between 2005 and 2010 (n=73,349), with follow-up through 2012. We used an extended Cox model to determine associations among the time-varying exposures, age (<65, 65-74, 75-84, and ≥85 years), eGFR (<6, 6-<9, 9-<12, 12-<15, and 15-<29 ml/min per 1.73 m2), and provision of dialysis, and survival.Result Over the mean±SEM follow-up of 3.4±2.2 years, 15% of patients started dialysis and 52% died. The eGFR at which dialysis, compared with medical management, associated with lower mortality varied by age (P<0.001). For patients aged <65, 65-74, 75-84, and ≥85 years, dialysis associated with lower mortality for those with eGFR not exceeding 6-<9, <6, 9-<12, and 9-<12 ml/min per 1.73 m2, respectively. Dialysis initiation at eGFR<6 ml/min per 1.73 m2 associated with a higher median life expectancy of 26, 25, and 19 months for patients aged 65, 75, and 85 years, respectively. When dialysis was initiated at eGFR 9-<12 ml/min per 1.73 m2, the estimated difference in median life expectancy was <1 year for these patients.Conclusions Provision of dialysis at higher levels of kidney function may extend survival for some older patients.

  View details for PubMedID 29789430

• Outcomes Associated With Left Ventricular Assist Devices Among Recipients With and Without End-stage Renal Disease JAMA INTERNAL MEDICINE Bansal, N., Hailpern, S. M., Katz, R., Hall, Y. N., Tamura, M. K., Kreuter, W., O'Hare, A. M. 2018; 178 (2): 204–9

  Abstract

  Left ventricular assist devices (LVADs) are widely used both as a bridge to heart transplant and as destination therapy in advanced heart failure. Although heart failure is common in patients with end-stage renal disease (ESRD), little is known about outcomes after LVAD implantation in this population.To determine the utilization of and outcomes associated with LVADs in nationally representative cohorts of patients with and without ESRD.We described LVAD utilization and outcomes among Medicare beneficiaries after ESRD onset (defined as having received maintenance dialysis or a kidney transplant) from 2003 to 2013 based on Medicare claims linked to data from the United States Renal Data System (USRDS), a national registry for ESRD. We compared Medicare beneficiaries with ESRD to a 5% sample of Medicare beneficiaries without ESRD.ESRD (vs no ESRD) among patients who underwent LVAD placement.The primary outcome was survival after LVAD placement.Among the patients with ESRD, the mean age was 58.4 (12.1) years and 62.0% (96) were male. Among those without ESRD, the mean age was 62.2 (12.6) years and 75.1% (196) were male. From 2003 to 2013, 155 Medicare beneficiaries with ESRD (median and interquartile range [IQR] days from ESRD onset to LVAD placement were 1655 days [453-3050 days]) and 261 beneficiaries without ESRD in the Medicare 5% sample received an LVAD. During a median follow-up of 762 days (IQR, 92-3850 days), 127 patients (81.9%) with and 95 (36.4%) without ESRD died. more than half of patients with ESRD (80 [51.6%]) compared with 11 (4%) of those without ESRD died during the index hospitalization. The median time to death was 16 days (IQR 2-447 days) for patients with ESRD compared with 2125 days (IQR, 565-3850 days) for those without ESRD. With adjustment for demographics, comorbidity and time period, patients with ESRD had a markedly increased adjusted risk of death (hazard ratio, 36.3; 95% CI, 15.6-84.5), especially in the first 60 days after LVAD placement.Patients with ESRD at the time of LVAD placement had an extremely poor prognosis, with most surviving for less than 3 weeks. This information may be crucial in supporting shared decision-making around treatments for advanced heart failure for patients with ESRD.

  View details for PubMedID 29255896

  View details for PubMedCentralID PMC5801100

• Hospice Use And End-Of-Life Spending Trajectories In Medicare Beneficiaries On Hemodialysis. Health affairs (Project Hope) O'Hare, A. M., Hailpern, S. M., Wachterman, M., Kreuter, W., Katz, R., Hall, Y. N., Montez-Rath, M., Tamura, M. K., Daratha, K. B. 2018; 37 (6): 980–87

  Abstract

  Infrequent and late referral to hospice among patients on dialysis likely reflects the impact of a Medicare payment policy that discourages the concurrent receipt of these services, but it may also reflect these patients' less predictable illness trajectories. Among a national cohort of patients on hemodialysis, we identified four distinct spending trajectories during the last year of life that represented markedly different intensities of care. Within the cohort, 9percent had escalating spending and 13percent had persistently high spending throughout the last year of life, while 41percent had relatively low spending with late escalation, and 37percent had moderate spending with late escalation. Across the four groups, the percentages of patients enrolled in hospice at the time of death were uniformly low ranging from only 19percent of those with persistently high costs to 21percent of those with moderate costs and the median number of days spent in hospice during the last year of life was virtually the same (either five or six days). These findings signal the need for greater flexibility in the provision of end-of-life care in this population.

  View details for PubMedID 29863925

• The Association of Sleep Duration and Quality with CKD Progression JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Ricardo, A. C., Knutson, K., Chen, J., Appel, L. J., Bazzano, L., Carmona-Powell, E., Cohan, J., Tamura, M., Steigerwalt, S., Thornton, J., Weir, M., Turek, N. F., Rahman, M., Van Cauter, E., Lash, J. P., Chronic Renal Insufficiency Cohort 2017; 28 (12): 3708–15

  Abstract

  Evidence suggests that sleep disorders are common in individuals with CKD, but the influence of sleep duration and quality on CKD progression is unknown. We examined the association of habitual sleep duration and quality with CKD progression in 431 Chronic Renal Insufficiency Cohort (CRIC) Study participants, of whom 48% were women and 50% had diabetes (mean age of 60 years old, mean eGFR =38 ml/min per 1.73 m2, and median urine protein-to-creatinine ratio [UPCR] =0.20 g/g). We assessed sleep duration and quality by 5-7 days of wrist actigraphy and self-report. Primary outcomes were incident ESRD, eGFR slope, log-transformed UPCR slope, and all-cause death. Participants slept an average of 6.5 hours per night; mean sleep fragmentation was 21%. Over a median follow-up of 5 years, we observed 70 ESRD events and 48 deaths. In adjusted analyses, greater sleep fragmentation associated with increased ESRD risk (hazard ratio, 1.04; 95% confidence interval, 1.01 to 1.07 per 1% increase in fragmentation). In adjusted mixed effects regression models, shorter sleep duration (per hour less) and greater sleep fragmentation (per 1% more) each associated with greater eGFR decline (-1.12 and -0.18 ml/min per 1.73 m2 per year, respectively; P=0.02 and P<0.01, respectively) and greater log UPCR slope (0.06/yr and 0.01/yr, respectively; P=0.02 and P<0.001, respectively). Self-reported daytime sleepiness associated with increased risk for all-cause death (hazard ratio, 1.11; 95% confidence interval, 1.02 to 1.20 per one-point increase in the Epworth Sleepiness Scale score). These findings suggest that short and poor-quality sleep are unrecognized risk factors for CKD progression.

  View details for PubMedID 28912373

  View details for PubMedCentralID PMC5698066

• Introduction to Patient-Reported Outcomes Perspectives Series CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. 2017; 12 (11): 1881

  View details for DOI 10.2215/CJN.07700717

  View details for Web of Science ID 000415700600023

  View details for PubMedID 28847908

  View details for PubMedCentralID PMC5672976

• Hospitalizations and Nursing Facility Stays During the Transition from CKD to ESRD on Dialysis: An Observational Study JOURNAL OF GENERAL INTERNAL MEDICINE Montez-Rath, M. E., Zheng, Y., Tamura, M., Grubbs, V., Winkelmayer, W. C., Chang, T. I. 2017; 32 (11): 1220–27

  Abstract

  There is little information on hospital and nursing facility stays during the transition from pre-dialysis kidney disease to end-stage renal disease treated with dialysis.To examine hospital and nursing facility stays in the years pre- and post-dialysis initiation, and to develop a novel method for visualizing these data.Observational study of patients in the US Renal Data System initiating dialysis from October 2011 to October 2012.Patients aged ≥67 years with Medicare Part A/B coverage for 1 year pre-dialysis initiation.Proportion of patients with ≥1 facility day, and among these, the mean number of days and the mean proportion of time spent in a facility in the first year post-dialysis initiation. We created "heat maps" to represent data visually.Among 28,049 patients, > 60% initiated dialysis in the hospital. Patients with at least 1 facility day spent 37-42 days in a facility in the year pre-dialysis initiation and 59-67 facility days in the year post-dialysis initiation. The duration of facility stay varied by age: patients aged 67-70 years spent 60 (95% CI 57-62) days or 25.8% of the first year post-dialysis initiation in a facility, while patients aged >80 years spent 67 (CI 65-69) days or 36.8% of the first year post-dialysis initiation in a facility. Patterns varied depending on the presence or absence of certain comorbid conditions, with dementia having a particularly large effect: patients with dementia spent approximately 50% of the first year post-dialysis initiation in a facility, regardless of age.Older patients, particularly octogenarians and patients with dementia or other comorbidities, spend a large proportion of time in a facility during the first year after dialysis initiation. Our heat maps provide a novel and concise visual representation of a large amount of quantitative data regarding expected outcomes after initiation of dialysis.

  View details for PubMedID 28808869

  View details for PubMedCentralID PMC5653560

• Receipt of Nephrology Care and Clinical Outcomes Among Veterans With Advanced CKD AMERICAN JOURNAL OF KIDNEY DISEASES Fung, E., Chang, T. I., Chertow, G. M., Thomas, I., Asch, S. M., Tamura, M. 2017; 70 (5): 705–14

  Abstract

  Clinical practice guidelines recommend referral to nephrology when estimated glomerular filtration rate (eGFR) decreases to <30mL/min/1.73m2; however, evidence for benefits of nephrology care are mixed.Observational cohort using landmark analysis.A national cohort of veterans with advanced chronic kidney disease, defined as an outpatient eGFR≤30mL/min/1.73m2 for January 1, 2010, through December 31, 2010, and a prior eGFR<60mL/min/1.73m2, using administrative and laboratory data from the Department of Veterans Affairs and the US Renal Data System.Receipt and frequency of outpatient nephrology care over 12 months.Survival and progression to end-stage renal disease (ESRD; receipt of dialysis or kidney transplantation) were the primary outcomes. In addition, control of associated clinical parameters over 12 months were intermediate outcomes.Of 39,669 patients included in the cohort, 14,983 (37.8%) received nephrology care. Older age, heart failure, dementia, depression, and rapidly declining kidney function were independently associated with the absence of nephrology care. During a mean follow-up of 2.9 years, 14,719 (37.1%) patients died and 4,310 (10.9%) progressed to ESRD. In models adjusting for demographics, comorbid conditions, and trajectory of kidney function, nephrology care was associated with lower risk for death (HR, 0.88; 95% CI, 0.85-0.91), but higher risk for ESRD (HR, 1.48; 95% CI, 1.38-1.58). Among patients with clinical parameters outside guideline recommendations at cohort entry, a significantly higher adjusted proportion of patients who received nephrology care had improvement in control of hemoglobin, potassium, albumin, calcium, and phosphorus concentrations compared with those who did not receive nephrology care.May not be generalizable to nonveterans.Among patients with advanced chronic kidney disease, nephrology care was associated with lower mortality, but was not associated with lower risk for progression to ESRD.

  View details for PubMedID 28811048

• Measures of Kidney Disease and the Risk of Venous Thromboembolism in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study AMERICAN JOURNAL OF KIDNEY DISEASES Cheung, K. L., Zakai, N. A., Folsom, A. R., Tamura, M., Peralta, C. A., Judd, S. E., Callas, P. W., Cushman, M. 2017; 70 (2): 182–90

  Abstract

  Kidney disease has been associated with venous thromboembolism (VTE) risk, but results conflict and there is little information regarding blacks.Prospective cohort study.30,239 black and white adults 45 years or older enrolled in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study 2003 to 2007.Estimated glomerular filtration rate (eGFR) using the combined creatinine-cystatin C (eGFRcr-cys) equation and urinary albumin-creatinine ratio (ACR).The primary outcome was adjudicated VTE, and secondary outcomes were provoked and unprovoked VTE, separately. Mortality was a competing-risk event.During 4.6 years of follow-up, 239 incident VTE events occurred over 124,624 person-years. Cause-specific HRs of VTE were calculated using proportional hazards regression adjusted for age, sex, race, region of residence, and body mass index. Adjusted VTE HRs for eGFRcr-cys of 60 to <90, 45 to <60, and <45 versus ≥90mL/min/1.73m2 were 1.28 (95% CI, 0.94-1.76), 1.30 (95% CI, 0.77-2.18), and 2.13 (95% CI, 1.21-3.76). Adjusted VTE HRs for ACR of 10 to <30, 30 to <300, and ≥300 versus <10mg/g were 1.14 (95% CI, 0.84-1.56), 1.15 (95% CI, 0.79-1.69), and 0.64 (95% CI, 0.25-1.62). Associations were similar for provoked and unprovoked VTE.Single measurement of eGFR and ACR may have led to misclassification. Smaller numbers of events may have limited power.There was an independent association of low eGFR (<45 vs ≥90mL/min/1.73m2) with VTE risk, but no association of ACR and VTE.

  View details for DOI 10.1053/j.ajkd.2016.10.039

  View details for Web of Science ID 000406047500011

  View details for PubMedID 28126238

  View details for PubMedCentralID PMC5522772

• Persistent Gaps in Use of Advance Directives Among Nursing Home Residents Receiving Maintenance Dialysis. JAMA internal medicine Kurella Tamura, M., Liu, S., Montez-Rath, M. E., O'Hare, A. M., Hall, Y. N., Lorenz, K. A. 2017

  View details for DOI 10.1001/jamainternmed.2017.1618

  View details for PubMedID 28520863

• Research Priorities for Palliative Care for Older Adults with Advanced Chronic Kidney Disease JOURNAL OF PALLIATIVE MEDICINE O'Hare, A. M., Song, M., Tamura, M. K., Moss, A. H. 2017; 20 (5): 453-460

  Abstract

  Older adults with advanced chronic kidney disease (CKD) often have multiple comorbid conditions, a high symptom burden, and limited life expectancy. There is mounting concern that the intensive patterns of care that many of these patients receive at the end of life are discordant with their values and preferences. The nephrology community has recognized that there are significant unmet palliative care needs in this population. In this article, we identify three broad areas of knowledge deficit where more evidence is needed to support the "best care possible" for this population: (1) what matters most to older adults with advanced CKD and their caregivers near the end of life; (2) how the nephrology community can best support older adults with advanced CKD to navigate complex treatment decisions throughout their illness; and (3) how the healthcare system should be reconfigured to promote patient- and family-centered care for older adults with advanced CKD. Research priorities include identifying opportunities for improving the end-of-life experience of older adults with CKD and their caregivers; developing and testing communication interventions before and during dialysis to ensure that treatment decisions reflect patients' preferences; and assessing the effectiveness of palliative care in improving quality of life for patients and caregivers, satisfaction with care, and aligning treatment decisions with patient goals and preferences.

  View details for DOI 10.1089/jpm.2016.0571

  View details for Web of Science ID 000400572600006

  View details for PubMedID 28463635

• Loss of executive function after dialysis initiation in adults with chronic kidney disease KIDNEY INTERNATIONAL Tamura, M. K., Vittinghoff, E., Hsu, C., Tam, K., Seliger, S. L., Sozio, S., Fischer, M., Chen, J., Lustigova, E., Strauss, L., Deo, R., Go, A. S., Yaffe, K. 2017; 91 (4): 948-953

  Abstract

  The association of dialysis initiation with changes in cognitive function among patients with advanced chronic kidney disease is poorly described. To better define this, we enrolled participants with advanced chronic kidney disease from the Chronic Renal Insufficiency Cohort in a prospective study of cognitive function. Eligible participants had a glomerular filtration rate of 20 ml/min/1.73m(2) or less, or dialysis initiation within the past two years. We evaluated cognitive function by a validated telephone battery at regular intervals over two years and analyzed test scores as z scores. Of 212 participants, 123 did not transition to dialysis during follow-up, 37 transitioned to dialysis after baseline, and 52 transitioned to dialysis prior to baseline. In adjusted analyses, the transition to dialysis was associated with a significant loss of executive function, but no significant changes in global cognition or memory. The estimated net difference in cognitive z scores at two years for participants who transitioned to dialysis during follow-up compared to participants who did not transition to dialysis was -0.01 (95% confidence interval -0.13, 0.11) for global cognition, -0.24 (-0.51, 0.03) for memory, and -0.33 (-0.60, -0.07) for executive function. Thus, among adults with advanced chronic kidney disease, dialysis initiation was associated with loss of executive function with no change in other aspects of cognition. Larger studies are needed to evaluate cognition during dialysis initiation.

  View details for Web of Science ID 000397835900023

  View details for PubMedCentralID PMC5357463

• TIMING OF HOSPICE ENROLLMENT AND END-OF-LIFE UTILIZATION AND SPENDING AMONG PATIENTS WITH END-STAGE RENAL DISEASE Wachterman, M. W., Hailpern, S., Keating, N. L., Tamura, M. K., O'Hare, A. SPRINGER. 2017: S354-S355

  View details for Web of Science ID 000440259001130

• Advance Directives and End-of-Life Care among Nursing Home Residents Receiving Maintenance Dialysis. Clinical journal of the American Society of Nephrology : CJASN Kurella Tamura, M., Montez-Rath, M. E., Hall, Y. N., Katz, R., O'Hare, A. M. 2017; 12 (3): 435-442

  Abstract

  Little is known about the relation between the content of advance directives and downstream treatment decisions among patients receiving maintenance dialysis. In this study, we determined the prevalence of advance directives specifying treatment limitations and/or surrogate decision-makers in the last year of life and their association with end-of-life care among nursing home residents.Using national data from 2006 to 2007, we compared the content of advance directives among 30,716 nursing home residents receiving dialysis to 30,825 nursing home residents with other serious illnesses during the year before death. Among patients receiving dialysis, we linked the content of advance directives to Medicare claims to ascertain site of death and treatment intensity in the last month of life.In the last year of life, 36% of nursing home residents receiving dialysis had a treatment-limiting directive, 22% had a surrogate decision-maker, and 13% had both in adjusted analyses. These estimates were 13%-27%, 5%-11%, and 6%-13% lower, respectively, than for decedents with other serious illnesses. For patients receiving dialysis who had both a treatment-limiting directive and surrogate decision-maker, the adjusted frequency of hospitalization, intensive care unit admission, intensive procedures, and inpatient death were lower by 13%, 17%, 13%, and 14%, respectively, and hospice use and dialysis discontinuation were 5% and 7% higher compared with patients receiving dialysis lacking both components.Among nursing home residents receiving dialysis, treatment-limiting directives and surrogates were associated with fewer intensive interventions and inpatient deaths, but were in place much less often than for nursing home residents with other serious illnesses.

  View details for DOI 10.2215/CJN.07510716

  View details for PubMedID 28057703

  View details for PubMedCentralID PMC5338713

• Advance Directives and End-of-Life Care among Nursing Home Residents Receiving Maintenance Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Montez-Rath, M. E., Hall, Y. N., Katz, R., O'Hare, A. M. 2017; 12 (3): 435-442

  Abstract

  Little is known about the relation between the content of advance directives and downstream treatment decisions among patients receiving maintenance dialysis. In this study, we determined the prevalence of advance directives specifying treatment limitations and/or surrogate decision-makers in the last year of life and their association with end-of-life care among nursing home residents.Using national data from 2006 to 2007, we compared the content of advance directives among 30,716 nursing home residents receiving dialysis to 30,825 nursing home residents with other serious illnesses during the year before death. Among patients receiving dialysis, we linked the content of advance directives to Medicare claims to ascertain site of death and treatment intensity in the last month of life.In the last year of life, 36% of nursing home residents receiving dialysis had a treatment-limiting directive, 22% had a surrogate decision-maker, and 13% had both in adjusted analyses. These estimates were 13%-27%, 5%-11%, and 6%-13% lower, respectively, than for decedents with other serious illnesses. For patients receiving dialysis who had both a treatment-limiting directive and surrogate decision-maker, the adjusted frequency of hospitalization, intensive care unit admission, intensive procedures, and inpatient death were lower by 13%, 17%, 13%, and 14%, respectively, and hospice use and dialysis discontinuation were 5% and 7% higher compared with patients receiving dialysis lacking both components.Among nursing home residents receiving dialysis, treatment-limiting directives and surrogates were associated with fewer intensive interventions and inpatient deaths, but were in place much less often than for nursing home residents with other serious illnesses.

  View details for DOI 10.2215/CJN.07510716

  View details for Web of Science ID 000396822000011

  View details for PubMedCentralID PMC5338713

• Inflammatory Markers and Risk for Cognitive Decline in Chronic Kidney Disease: The CRIC Study. Kidney international reports Kurella Tamura, M., Tam, K., Vittinghoff, E., Raj, D., Sozio, S. M., Rosas, S. E., Makos, G., Lora, C., He, J., Go, A. S., Hsu, C., Yaffe, K. 2017; 2 (2): 192-200

  Abstract

  Chronic kidney disease (CKD) is associated with an increased risk of cognitive decline, but the mechanisms remain poorly defined. We sought to determine the relation between serum inflammatory markers and risk of cognitive decline among adults with CKD.We studied 757 adults aged ≥55 years with CKD participating in the Chronic Renal Insufficiency Cohort Cognitive study. We measured interleukin (IL)-1β, IL-1 receptor antagonist, IL-6, tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein (hs-CRP), and fibrinogen in baseline plasma samples. We assessed cognitive function at regular intervals in 4 domains and defined incident impairment as a follow-up score more than 1 SD poorer than the group mean.The mean age of the sample was 64.3 ± 5.6 years, and the mean follow-up was 6.2 ± 2.5 years. At baseline, higher levels of each inflammatory marker were associated with poorer age-adjusted performance. In analyses adjusted for baseline cognition, demographics, comorbid conditions, and kidney function, participants in the highest tertile of hs-CRP, the highest tertile of fibrinogen, and the highest tertile of IL-1β had an increased risk of impairment in attention compared to participants in the lowest tertile of each marker. Participants in the highest versus lowest tertile of TNF-α had a lower adjusted risk of impairment in executive function. There was no association between other inflammatory markers and change in cognitive function.Among adults with CKD, higher levels of hs-CRP, fibrinogen, and IL-1β were associated with a higher risk of impairment in attention. Higher levels of TNF-α were associated with a lower risk of impaired executive function.

  View details for DOI 10.1016/j.ekir.2016.10.007

  View details for PubMedID 28439566

• Optimizing the Transition to End-Stage Renal Disease SEMINARS IN NEPHROLOGY Tamura, M. 2017; 37 (2): 113

  View details for DOI 10.1016/j.semnephrol.2016.12.010

  View details for Web of Science ID 000399852900001

  View details for PubMedID 28410644

• Loss of executive function after dialysis initiation in adults with chronic kidney disease. Kidney international Kurella Tamura, M., Vittinghoff, E., Hsu, C., Tam, K., Seliger, S. L., Sozio, S., Fischer, M., Chen, J., Lustigova, E., Strauss, L., Deo, R., Go, A. S., Yaffe, K. 2017

  Abstract

  The association of dialysis initiation with changes in cognitive function among patients with advanced chronic kidney disease is poorly described. To better define this, we enrolled participants with advanced chronic kidney disease from the Chronic Renal Insufficiency Cohort in a prospective study of cognitive function. Eligible participants had a glomerular filtration rate of 20 ml/min/1.73m(2) or less, or dialysis initiation within the past two years. We evaluated cognitive function by a validated telephone battery at regular intervals over two years and analyzed test scores as z scores. Of 212 participants, 123 did not transition to dialysis during follow-up, 37 transitioned to dialysis after baseline, and 52 transitioned to dialysis prior to baseline. In adjusted analyses, the transition to dialysis was associated with a significant loss of executive function, but no significant changes in global cognition or memory. The estimated net difference in cognitive z scores at two years for participants who transitioned to dialysis during follow-up compared to participants who did not transition to dialysis was -0.01 (95% confidence interval -0.13, 0.11) for global cognition, -0.24 (-0.51, 0.03) for memory, and -0.33 (-0.60, -0.07) for executive function. Thus, among adults with advanced chronic kidney disease, dialysis initiation was associated with loss of executive function with no change in other aspects of cognition. Larger studies are needed to evaluate cognition during dialysis initiation.

  View details for DOI 10.1016/j.kint.2016.11.015

  View details for PubMedID 28139292

• Effect of a Dialysis Access Coordinator on Preemptive Access Placement among Veterans: A Quality Improvement Initiative AMERICAN JOURNAL OF NEPHROLOGY Gale, R. C., Kehoe, D., Lit, Y. Z., Asch, S. M., Tamura, M. K. 2017; 45 (1): 14-21

  Abstract

  Preemptive placement of permanent dialysis access is recommended in order to reduce the morbidity associated with central venous catheters. We assessed the effect of a dialysis access coordinator on preemptive access placement in veterans who are at high risk for end-stage renal disease (ESRD).Pre-post evaluation of a dialysis access coordinator in the nephrology clinics of the Veterans Affairs Palo Alto. The access coordinator streamlined access referrals, prioritized surgical waiting lists and addressed patient barriers. We compared the frequency of preemptive access referral, surgery, and use for dialysis during the intervention period, July 1, 2013 to May 31, 2016, to a pre-intervention period, January 1, 2011 to December 31, 2013, among all patients with a predicted 1-year risk for ESRD ≥20%.There were 156 patients in the historical cohort and 131 in the intervention cohort. The mean age was 69.9 ± 11.6 years and the mean estimated glomerular filtration rate was 14.5 ± 5.7 ml/min/1.73 m2. The intervention was associated with an 11.8% increase in access referral (p value = 0.03), and a 9.4% increase in completed access surgery (p value = 0.05). Increases in permanent access at the start of dialysis (15.2%), and functional permanent access at the start of dialysis (12.4%) did not reach statistical significance. Among patients who received access surgery, there was no significant difference in the prevalence of unused access.Implementation of an access coordinator was associated with a modest increase in preemptive access placement among patients who are at high risk for ESRD without increasing the prevalence of unused access.

  View details for DOI 10.1159/000452346

  View details for Web of Science ID 000391428900003

• Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT). American journal of kidney diseases : the official journal of the National Kidney Foundation Weiner, D. E., Gaussoin, S. A., Nord, J. n., Auchus, A. P., Chelune, G. J., Chonchol, M. n., Coker, L. n., Haley, W. E., Killeen, A. A., Kimmel, P. L., Lerner, A. J., Oparil, S. n., Saklayen, M. G., Slinin, Y. M., Wright, C. B., Williamson, J. D., Kurella Tamura, M. n. 2017; 70 (3): 357–67

  Abstract

  Chronic kidney disease is common and is associated with cardiovascular disease, cerebrovascular disease, and cognitive function, although the nature of this relationship remains uncertain.Cross-sectional cohort using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT).Participants in SPRINT, a randomized clinical trial of blood pressure targets in older community-dwelling adults with cardiovascular disease, chronic kidney disease, or high cardiovascular disease risk and without diabetes or known stroke, who underwent detailed neurocognitive testing in the cognition substudy, SPRINT-Memory and Cognition in Decreased Hypertension (SPRINT-MIND).Urine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR).Cognitive function, a priori defined as 5 cognitive domains based on 11 cognitive tests using z scores, and abnormal white matter volume quantified by brain magnetic resonance imaging.Of 9,361 SPRINT participants, 2,800 participated in SPRINT-MIND and 2,707 had complete data; 637 had brain imaging. Mean age was 68 years, 37% were women, 30% were black, and 20% had known cardiovascular disease. Mean eGFR was 70.8±20.9mL/min/1.73m2 and median urine ACR was 9.7 (IQR, 5.7-22.5) mg/g. In adjusted analyses, higher ACR was associated with worse global cognitive function, executive function, memory, and attention, such that each doubling of urine ACR had the same association with cognitive performance as being 7, 10, 6, and 14 months older, respectively. Lower eGFR was independently associated with worse global cognitive function and memory. In adjusted models, higher ACR, but not eGFR, was associated with larger abnormal white matter volume.Cross-sectional only, no patients with diabetes were included.In older adults, higher urine ACR and lower eGFR have independent associations with global cognitive performance with different affected domains. Albuminuria concurrently identifies a higher burden of abnormal brain white matter disease, suggesting that vascular disease may mediate these relationships.

  View details for PubMedID 28606731

  View details for PubMedCentralID PMC5572661

• Trends in Receipt of Intensive Procedures at the End of Life Among Patients Treated With Maintenance Dialysis AMERICAN JOURNAL OF KIDNEY DISEASES Eneanya, N. D., Hailpern, S. M., O'Hare, A. M., Tamura, M. K., Katz, R., Kreuter, W., Montez-Rath, M. E., Hebert, P. L., Hall, Y. N. 2017; 69 (1): 60-68

  Abstract

  Many dialysis patients receive intensive procedures intended to prolong life at the very end of life. However, little is known about trends over time in the use of these procedures. We describe temporal trends in receipt of inpatient intensive procedures during the last 6 months of life among patients treated with maintenance dialysis.Mortality follow-back study.649,607 adult Medicare beneficiaries on maintenance dialysis therapy who died in 2000 to 2012.Period of death (2000-2003, 2004-2008, or 2009-2012), age at time of death (18-59, 60-64, 65-69, 70-74, 75-79, 80-84, and ≥85 years), and race/ethnicity (Hispanic, non-Hispanic black, or non-Hispanic white).Receipt of an inpatient intensive procedure (defined as invasive mechanical ventilation/intubation, tracheostomy, gastrostomy/jejunostomy tube insertion, enteral or parenteral nutrition, or cardiopulmonary resuscitation) during the last 6 months of life.Overall, 34% of cohort patients received an intensive procedure in the last 6 months of life, increasing from 29% in 2000 to 36% in 2012 (with 2000-2003 as the referent category; adjusted risk ratios [RRs] were 1.06 [95% CI, 1.05-1.07] and 1.10 [95% CI, 1.09-1.12] for 2004-2008 and 2009-2012, respectively). Use of intensive procedures increased more markedly over time in younger versus older patients (comparing 2009-2012 to 2000-2003, adjusted RR was 1.18 [95% CI, 1.15-1.20] for the youngest age group as opposed to 1.00 [95% CI, 0.96-1.04] for the oldest group). Comparing 2009 to 2012 to 2000 to 2003, the use of intensive procedures increased more dramatically for Hispanic patients than for non-Hispanic black or non-Hispanic white patients (adjusted RRs of 1.18 [95% CI, 1.14-1.22], 1.09 [95% CI, 1.07-1.11], and 1.10 [95% CI, 1.08-1.12], respectively).Data sources do not provide insight into reasons for observed trends in the use of intensive procedures.Among patients treated with maintenance dialysis, there is a trend toward more frequent use of intensive procedures at the end of life, especially in younger patients and those of Hispanic ethnicity.

  View details for DOI 10.1053/j.ajkd.2016.07.028

  View details for Web of Science ID 000390526300014

  View details for PubMedCentralID PMC5182121

• Metabolic Profiling of Impaired Cognitive Function in Patients Receiving Dialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Chertow, G. M., Depner, T. A., Nissenson, A. R., Schiller, B., Mehta, R. L., Liu, S., Sirich, T. L. 2016; 27 (12): 3780-3787

  Abstract

  Retention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients participating in a trial of frequent hemodialysis. We assessed executive function with the Trail Making Test Part B and the Digit Symbol Substitution test. Impaired executive function was defined as a score ≥2 SDs below normative values. Four metabolites-4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline-were associated with impaired executive function at the false-detection rate significance threshold. After adjustment for demographic and clinical characteristics, the associations remained statistically significant: relative risk 1.16 (95% confidence interval [95% CI], 1.03 to 1.32), 1.39 (95% CI, 1.13 to 1.71), 1.24 (95% CI, 1.03 to 1.50), and 1.20 (95% CI, 1.05 to 1.38) for each SD increase in 4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline, respectively. The association between 4-hydroxyphenylacetate and impaired executive function was replicated in the second cohort (relative risk 1.12; 95% CI, 1.02 to 1.23), whereas the associations for phenylacetylglutamine, hippurate, and prolyl-hydroxyproline did not reach statistical significance in this cohort. In summary, four metabolites related to phenylalanine, benzoate, and glutamate metabolism may be markers of cognitive impairment in patients receiving maintenance dialysis.

  View details for DOI 10.1681/ASN.2016010039

  View details for PubMedID 27444566

• Recognition for Conservative Care in Kidney Failure AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M. 2016; 68 (5): 671-673

  View details for DOI 10.1053/j.ajkd.2016.08.009

  View details for Web of Science ID 000389511300006

  View details for PubMedID 27595396

• Re-evaluation of re-hospitalization and rehabilitation in renal research. Hemodialysis international. International Symposium on Home Hemodialysis Lin, E., Kurella Tamura, M., Montez-Rath, M. E., Chertow, G. M. 2016

  Abstract

  Introduction The use of administrative data to capture 30-day readmission rates in end-stage renal disease is challenging since Medicare combines claims from acute care, inpatient rehabilitation (IRF), and long-term care hospital stays into a single "Inpatient" file. For data prior to 2012, the United States Renal Data System does not contain the variables necessary to easily identify different facility types, making it likely that prior studies have inaccurately estimated 30-day readmission rates. Methods For this report, we developed two methods (a "simple method" and a "rehabilitation-adjusted method") to identify acute care, IRF, and long-term care hospital stays from United States Renal Data System claims data, and compared them to methods used in previously published reports. Findings We found that prior methods overestimated 30-day readmission rates by up to 12.3% and overestimated average 30-day readmission costs by up to 11%. In contrast, the simple and rehabilitation-adjusted methods overestimated 30-day readmission rates by 0.1% and average 30-day readmission costs by 1.8%. The rehabilitation-adjusted method also accurately identified 96.8% of IRF stays. Discussion Prior research has likely provided inaccurate estimates of 30-day readmissions in patients undergoing dialysis. In the absence of data on specific facility types particularly when using data prior to 2012, future researchers could employ our method to more accurately characterize 30-day readmission rates and associated outcomes in patients with end-stage renal disease.

  View details for DOI 10.1111/hdi.12497

  View details for PubMedID 27766736

• Supportive Care: Economic Considerations in Advanced Kidney Disease CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Morton, R. L., Tamura, M., Coast, J., Davison, S. N. 2016; 11 (10): 1915-1920

  Abstract

  Kidney supportive care describes multiple interventions for patients with advanced CKD that focus on improving the quality of life and addressing what matters most to patients. This includes shared decision making and aligning treatment plans with patient goals through advance care planning and providing relief from pain and other distressing symptoms. Kidney supportive care is an essential component of quality care throughout the illness trajectory. However, in the context of limited health care resources, evidence of its cost-effectiveness is required to support decisions regarding appropriate resource allocation. We review the literature and outline the evidence gaps and particular issues associated with measuring the costs, benefits, and cost-effectiveness of kidney supportive care. We find evidence that the dominant evaluative framework of a cost per quality-adjusted life year may not be suitable for evaluations in this context and that relevant outcomes may include broader measures of patient wellbeing, having care aligned with treatment preferences, and family satisfaction with the end of life care experience. To improve the evidence base for the cost-effectiveness of kidney supportive care, large prospective cohort studies are recommended to collect data on both resource use and health outcomes and should include patients who receive conservative kidney management without dialysis. Linkage to administrative datasets, such as Medicare, Hospital Episode Statistics, and the Pharmaceutical Benefits Scheme for prescribed medicines, can provide a detailed estimate of publicly funded resource use and reduce the burden of data collection for patients and families. Longitudinal collection of quality of life and functional status should be added to existing cohort or kidney registry studies. Interventions that improve health outcomes for people with advanced CKD, such as kidney supportive care, not only have the potential to improve quality of life, but also may reduce the high costs associated with unwanted hospitalization and intensive medical treatments.

  View details for DOI 10.2215/CJN.12651115

  View details for Web of Science ID 000384830500027

  View details for PubMedID 27510455

  View details for PubMedCentralID PMC5053800

• Trends in Receipt of Intensive Procedures at the End of Life Among Patients Treated With Maintenance Dialysis. American journal of kidney diseases Eneanya, N. D., Hailpern, S. M., O'Hare, A. M., Kurella Tamura, M., Katz, R., Kreuter, W., Montez-Rath, M. E., Hebert, P. L., Hall, Y. N. 2016

  Abstract

  Many dialysis patients receive intensive procedures intended to prolong life at the very end of life. However, little is known about trends over time in the use of these procedures. We describe temporal trends in receipt of inpatient intensive procedures during the last 6 months of life among patients treated with maintenance dialysis.Mortality follow-back study.649,607 adult Medicare beneficiaries on maintenance dialysis therapy who died in 2000 to 2012.Period of death (2000-2003, 2004-2008, or 2009-2012), age at time of death (18-59, 60-64, 65-69, 70-74, 75-79, 80-84, and ≥85 years), and race/ethnicity (Hispanic, non-Hispanic black, or non-Hispanic white).Receipt of an inpatient intensive procedure (defined as invasive mechanical ventilation/intubation, tracheostomy, gastrostomy/jejunostomy tube insertion, enteral or parenteral nutrition, or cardiopulmonary resuscitation) during the last 6 months of life.Overall, 34% of cohort patients received an intensive procedure in the last 6 months of life, increasing from 29% in 2000 to 36% in 2012 (with 2000-2003 as the referent category; adjusted risk ratios [RRs] were 1.06 [95% CI, 1.05-1.07] and 1.10 [95% CI, 1.09-1.12] for 2004-2008 and 2009-2012, respectively). Use of intensive procedures increased more markedly over time in younger versus older patients (comparing 2009-2012 to 2000-2003, adjusted RR was 1.18 [95% CI, 1.15-1.20] for the youngest age group as opposed to 1.00 [95% CI, 0.96-1.04] for the oldest group). Comparing 2009 to 2012 to 2000 to 2003, the use of intensive procedures increased more dramatically for Hispanic patients than for non-Hispanic black or non-Hispanic white patients (adjusted RRs of 1.18 [95% CI, 1.14-1.22], 1.09 [95% CI, 1.07-1.11], and 1.10 [95% CI, 1.08-1.12], respectively).Data sources do not provide insight into reasons for observed trends in the use of intensive procedures.Among patients treated with maintenance dialysis, there is a trend toward more frequent use of intensive procedures at the end of life, especially in younger patients and those of Hispanic ethnicity.

  View details for DOI 10.1053/j.ajkd.2016.07.028

  View details for PubMedID 27693262

  View details for PubMedCentralID PMC5182121

• Measuring vascular reactivity with resting-state blood oxygenation level-dependent (BOLD) signal fluctuations: A potential alternative to the breath-holding challenge? Journal of cerebral blood flow and metabolism Jahanian, H., Christen, T., Moseley, M. E., Pajewski, N. M., Wright, C. B., Tamura, M. K., Zaharchuk, G. 2016

  Abstract

  Measurement of the ability of blood vessels to dilate and constrict, known as vascular reactivity, is often performed with breath-holding tasks that transiently raise arterial blood carbon dioxide (PaCO2) levels. However, following the proper commands for a breath-holding experiment may be difficult or impossible for many patients. In this study, we evaluated two approaches for obtaining vascular reactivity information using blood oxygenation level-dependent signal fluctuations obtained from resting-state functional magnetic resonance imaging data: physiological fluctuation regression and coefficient of variation of the resting-state functional magnetic resonance imaging signal. We studied a cohort of 28 older adults (69 ± 7 years) and found that six of them (21%) could not perform the breath-holding protocol, based on an objective comparison with an idealized respiratory waveform. In the subjects that could comply, we found a strong linear correlation between data extracted from spontaneous resting-state functional magnetic resonance imaging signal fluctuations and the blood oxygenation level-dependent percentage signal change during breath-holding challenge ( R(2 )= 0.57 and 0.61 for resting-state physiological fluctuation regression and resting-state coefficient of variation methods, respectively). This technique may eliminate the need for subject cooperation, thus allowing the evaluation of vascular reactivity in a wider range of clinical and research conditions in which it may otherwise be impractical.

  View details for PubMedID 27683452

• Cognitive Impairment and Progression of CKD AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M. K., Yaffe, K., Hsu, C., Yang, J., Sozio, S., Fischer, M., Chen, J., Ojo, A., DeLuca, J., Xie, D., Vittinghoff, E., Go, A. S. 2016; 68 (1): 77-83

  Abstract

  Cognitive impairment is common among patients with chronic kidney disease (CKD); however, its prognostic significance is unclear. We assessed the independent association between cognitive impairment and CKD progression in adults with mild to moderate CKD.Prospective cohort.Adults with CKD participating in the CRIC (Chronic Renal Insufficiency Cohort) Study. Mean age of the sample was 57.7±11.0 years and mean estimated glomerular filtration rate (eGFR) was 45.0±16.9mL/min/1.73m(2).Cognitive function was assessed with the Modified Mini-Mental State Examination at study entry. A subset of participants 55 years and older underwent 5 additional cognitive tests assessing different domains. Cognitive impairment was defined as a score > 1 SD below the mean score on each test. Covariates included demographics, kidney function, comorbid conditions, and medications.Incident end-stage renal disease (ESRD) and incident ESRD or 50% decline in baseline eGFR.In 3,883 CRIC participants, 524 (13.5%) had cognitive impairment at baseline. During a median 6.1 years of follow-up, 813 developed ESRD and 1,062 developed ESRD or a ≥50% reduction in eGFR. There was no significant association between cognitive impairment and risk for ESRD (HR, 1.07; 95% CI, 0.87-1.30) or the composite of ESRD or 50% reduction in eGFR (HR, 1.06; 95% CI, 0.89-1.27). Similarly, there was no association between cognitive impairment and the joint outcome of death, ESRD, or 50% reduction in eGFR (HR, 1.06; 95% CI, 0.91-1.23). Among CRIC participants who underwent additional cognitive testing, we found no consistent association between impairment in specific cognitive domains and risk for CKD progression in adjusted analyses.Unmeasured potential confounders, single measure of cognition for younger participants.Among adults with CKD, cognitive impairment is not associated with excess risk for CKD progression after accounting for traditional risk factors.

  View details for DOI 10.1053/j.ajkd.2016.01.026

  View details for Web of Science ID 000378636100016

  View details for PubMedCentralID PMC4921255

• A survey of views and practice patterns of dialysis medical directors toward end-of-life decision making for patients with end-stage renal disease. Palliative medicine Fung, E., Slesnick, N., Kurella Tamura, M., Schiller, B. 2016; 30 (7): 653-660

  Abstract

  Patients with end-stage renal disease report infrequent end-of-life discussions, and nephrology trainees report feeling unprepared for end-of-life decision making, but the views of dialysis medical directors have not been studied.Our objective is to understand dialysis medical directors' views and practice patterns on end-of-life decision making for patients with ESRD.We administered questionnaires to dialysis medical directors during medical director meetings of three different dialysis organizations in 2013. Survey questions corresponded to recommendations from the Renal Physicians Association clinical practice guidelines on initiation and withdrawal of dialysis.There were 121 medical director respondents from 28 states.The majority of respondents felt "very prepared" (66%) or "somewhat prepared" (29%) to participate in end-of-life decisions and most (80%) endorsed a model of shared decision making. If asked to do so, 70% of the respondents provided prognostic information "often" or "nearly always." For patients with a poor prognosis, 36% of respondents would offer a time-limited trial of dialysis "often" or "nearly always", while 56% of respondents would suggest withdrawal from dialysis "often" or "nearly always" for those with a poor prognosis currently receiving dialysis therapy. Patient resistance and fear of taking away hope were the most commonly cited barriers to end-of-life discussions.Views and reported practice patterns of medical directors are consistent with clinical practice guidelines for end-of-life decision making for patients with end-stage renal disease but inconsistent with patient perceptions.

  View details for DOI 10.1177/0269216315625856

  View details for PubMedID 26814215

• Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults NEUROLOGY Tamura, M. K., Pajewski, N. M., Bryan, R. N., Weiner, D. E., Diamond, M., Van Buren, P., Taylor, A., Beddhu, S., Rosendorff, C., Jahanian, H., Zaharchuk, G. 2016; 86 (13): 1208-1216

  Abstract

  To determine the relation between markers of kidney disease-estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR)-with cerebral blood flow (CBF) and white matter volume (WMV) in hypertensive adults.We used baseline data collected from 665 nondiabetic hypertensive adults aged ≥50 years participating in the Systolic Blood Pressure Intervention Trial (SPRINT). We used arterial spin labeling to measure CBF and structural 3T images to segment tissue into normal and abnormal WMV. We used quantile regression to estimate the association between eGFR and UACR with CBF and abnormal WMV, adjusting for sociodemographic and clinical characteristics.There were 218 participants (33%) with eGFR <60 mL/min/1.73 m(2) and 146 participants (22%) with UACR ≥30 mg/g. Reduced eGFR was independently associated with higher adjusted median CBF, but not with abnormal WMV. Conversely, in adjusted analyses, there was a linear independent association between UACR and larger abnormal WMV, but not with CBF. Compared to participants with neither marker of CKD (eGFR ≥60 mL/min/1.73 m(2) and UACR <30 mg/g), median CBF was 5.03 mL/100 g/min higher (95% confidence interval [CI] 0.78, 9.29) and abnormal WMV was 0.63 cm(3) larger (95% CI 0.08, 1.17) among participants with both markers of CKD (eGFR <60 mL/min/1.73 m(2) and UACR ≥30 mg/g).Among nondiabetic hypertensive adults, reduced eGFR was associated with higher CBF and higher UACR was associated with larger abnormal WMV.

  View details for DOI 10.1212/WNL.0000000000002527

  View details for Web of Science ID 000372853000007

  View details for PubMedCentralID PMC4818564

• Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults. Neurology Kurella Tamura, M., Pajewski, N. M., Bryan, R. N., Weiner, D. E., Diamond, M., Van Buren, P., Taylor, A., Beddhu, S., Rosendorff, C., Jahanian, H., Zaharchuk, G. 2016; 86 (13): 1208-1216

  Abstract

  To determine the relation between markers of kidney disease-estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR)-with cerebral blood flow (CBF) and white matter volume (WMV) in hypertensive adults.We used baseline data collected from 665 nondiabetic hypertensive adults aged ≥50 years participating in the Systolic Blood Pressure Intervention Trial (SPRINT). We used arterial spin labeling to measure CBF and structural 3T images to segment tissue into normal and abnormal WMV. We used quantile regression to estimate the association between eGFR and UACR with CBF and abnormal WMV, adjusting for sociodemographic and clinical characteristics.There were 218 participants (33%) with eGFR <60 mL/min/1.73 m(2) and 146 participants (22%) with UACR ≥30 mg/g. Reduced eGFR was independently associated with higher adjusted median CBF, but not with abnormal WMV. Conversely, in adjusted analyses, there was a linear independent association between UACR and larger abnormal WMV, but not with CBF. Compared to participants with neither marker of CKD (eGFR ≥60 mL/min/1.73 m(2) and UACR <30 mg/g), median CBF was 5.03 mL/100 g/min higher (95% confidence interval [CI] 0.78, 9.29) and abnormal WMV was 0.63 cm(3) larger (95% CI 0.08, 1.17) among participants with both markers of CKD (eGFR <60 mL/min/1.73 m(2) and UACR ≥30 mg/g).Among nondiabetic hypertensive adults, reduced eGFR was associated with higher CBF and higher UACR was associated with larger abnormal WMV.

  View details for DOI 10.1212/WNL.0000000000002527

  View details for PubMedID 26920359

• Anemia and risk for cognitive decline in chronic kidney disease BMC NEPHROLOGY Tamura, M. K., Vittinghoff, E., Yang, J., Go, A. S., Seliger, S. L., Kusek, J. W., Lash, J., Cohen, D. L., Simon, J., Batuman, V., Ordonez, J., Makos, G., Yaffe, K. 2016; 17

  Abstract

  Anemia is common among patients with chronic kidney disease (CKD) but its health consequences are poorly defined. The aim of this study was to determine the relationship between anemia and cognitive decline in older adults with CKD.We studied a subgroup of 762 adults age ≥55 years with CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) study. Anemia was defined according to the World Health Organization criteria (hemoglobin <13 g/dL for men and <12 g/dL for women). Cognitive function was assessed annually with a battery of six tests. We used logistic regression to determine the association between anemia and baseline cognitive impairment on each test, defined as a cognitive score more than one standard deviation from the mean, and mixed effects models to determine the relation between anemia and change in cognitive function during follow-up after adjustment for demographic and clinical characteristics.Of 762 participants with mean estimated glomerular filtration rate of 42.7 ± 16.4 ml/min/1.73 m(2), 349 (46 %) had anemia. Anemia was not independently associated with baseline cognitive impairment on any test after adjustment for demographic and clinical characteristics. Over a median 2.9 (IQR 2.6-3.0) years of follow-up, there was no independent association between anemia and change in cognitive function on any of the six cognitive tests.Among older adults with CKD, anemia was not independently associated with baseline cognitive function or decline.

  View details for DOI 10.1186/s12882-016-0226-6

  View details for Web of Science ID 000369153500001

  View details for PubMedCentralID PMC4730636

• Epidemiology and Public Health Concerns of CKD in Older Adults ADVANCES IN CHRONIC KIDNEY DISEASE Fung, E., Tamura, M. K. 2016; 23 (1): 8-11

  Abstract

  CKD is increasingly common in older adults. Estimating the glomerular filtration rate can be challenging in this population, with sarcopenia affecting the accuracy of various formulae. Competing risks of death influence the risk of progression to end-stage kidney disease. In managing CKD in this population, one must take into consideration other comorbidities including assessment of geriatric syndromes. More research is still needed to guide medical management in this heterogeneous population.

  View details for DOI 10.1053/j.ackd.2015.10.001

  View details for Web of Science ID 000368652200003

  View details for PubMedCentralID PMC4693627

• Prevalence and correlates of functional dependence among maintenance dialysis patients HEMODIALYSIS INTERNATIONAL Kavanagh, N. T., Schiller, B., Saxena, A. B., Thomas, I., Tamura, M. K. 2015; 19 (4): 593-600

  Abstract

  Functional dependence is an important determinant of longevity and quality of life. The purpose of the current study was to determine the prevalence and correlates of functional dependence among patients with end-stage renal disease (ESRD) receiving maintenance dialysis. We enrolled 148 participants with ESRD from five clinics. Functional status, as measured by basic and instrumental activities of daily living (ADL, IADL), was ascertained by validated questionnaires. Functional dependence was defined as needing assistance in at least one of seven IADLs or at least one of four ADLs. Demographic characteristics, chronic health conditions, anthropometric measurements, and laboratories were assessed by a combination of self-report and chart review. Cognitive function was assessed with a neurocognitive battery, and depressive symptoms were assessed by questionnaire. Mean age of the sample was 56.2 ± 14.6 years. Eighty-seven participants (58.8%) demonstrated dependence in ADLs or IADLs, 70 (47.2%) exhibited IADL dependence alone, and 17 (11.5%) exhibited combined IADL and ADL dependence. In a multivariable-adjusted model, stroke, cognitive impairment, and higher systolic blood pressure were independent correlates of functional dependence. We found no significant association between demographic characteristics, chronic health conditions, depressive symptoms or laboratory measurements, and functional dependence. Impairment in executive function was more strongly associated with functional dependence than memory impairment. Functional dependence is common among ESRD patients and independently associated with stroke, systolic blood pressure, and executive function impairment.

  View details for DOI 10.1111/hdi.12286

  View details for Web of Science ID 000362584500030

• Menopausal symptoms in women with chronic kidney disease. Menopause (New York, N.Y.) Cheung, K. L., Stefanick, M. L., Allison, M. A., LeBlanc, E. S., Vitolins, M. Z., Shara, N., Chertow, G. M., Winkelmayer, W. C., Kurella Tamura, M. 2015; 22 (9): 1006-1011

  Abstract

  This study aims to determine whether menopausal symptoms differed between women with chronic kidney disease (CKD) and women without CKD, and whether CKD modified associations of late vasomotor symptoms (VMS) with mortality and/or cardiovascular events.CKD, defined as estimated glomerular filtration rate lower than 60 mL/minute/1.73 m (using the Chronic Kidney Disease Epidemiology Collaboration equation), was determined in 17,891 postmenopausal women, aged 50 to 79 years at baseline, in the multiethnic Women's Health Initiative cohort. Primary outcomes were presence, severity, and timing/duration of VMS (self-reported hot flashes and night sweats) at baseline. We used polytomous logistic regression to test for associations among CKD and four VMS categories (no VMS; early VMS-present before menopause but not at study baseline; late VMS-present only at study baseline; persistent VMS-present before menopause and study baseline) and Cox regression to determine whether CKD modified associations between late VMS and mortality or cardiovascular events.Women with CKD (1,017 of 17,891; mean estimated glomerular filtration rate, 50.7 mL/min/1.73 m) were more likely to have had menopause before age 45 years (26% vs 23%, P = 0.02) but were less likely to experience VMS (38% vs 46%, P < 0.001) than women without CKD. Women with CKD were not more likely than women without CKD to experience late VMS. Late VMS (hazard ratio, 1.16; 95% CI, 1.04-1.29) and CKD (hazard ratio, 1.74; 95% CI, 1.54-1.97) were each independently associated with increased risk for mortality, but CKD did not modify the association of late VMS with mortality (Pinteraction = 0.53), coronary heart disease (Pinteraction = 0.12), or stroke (Pinteraction = 0.68).Women with mild CKD experience earlier menopause and fewer VMS than women without CKD.

  View details for DOI 10.1097/GME.0000000000000416

  View details for PubMedID 25628057

• US Renal Data System 2014 Annual Data Report: Epidemiology of Kidney Disease in the United States AMERICAN JOURNAL OF KIDNEY DISEASES Saran, R., Li, Y., Robinson, B., Ayanian, J., Balkrishnan, R., Bragg-Gresham, J., Chen, J. L., Cope, E., Gipson, D., He, K., Herman, W., Heung, M., Hirth, R. A., Jacobsen, S. S., Kalantar-Zadeh, K., Kovesdy, C. P., Leichtman, A. B., Lu, Y., Molnar, M. Z., Morgenstern, H., Nallamothu, B., O'Hare, A. M., Pisoni, R., Plattner, B., Port, F. K., Rao, P., Rhee, C. M., Schaubel, D. E., Selewski, D. T., Shahinian, V., Sim, J. J., Song, P., Streja, E., Tamura, M., Tentori, F., Eggers, P. W., Agodoa, L. C., Abbott, K. C. 2015; 66 (1): S1-+

  View details for DOI 10.1053/j.ajkd.2015.05.001

  View details for Web of Science ID 000356729900001

  View details for PubMedID 26111994

  View details for PubMedCentralID PMC6643986

• Overlooked care transitions: an opportunity to reduce acute care use in ESRD. Clinical journal of the American Society of Nephrology Erickson, K. F., Kurella Tamura, M. 2015; 10 (3): 347-349

  View details for DOI 10.2215/CJN.00220115

  View details for PubMedID 25649156

  View details for PubMedCentralID PMC4348670

• Introduction: Sleep and Neurologic Disorders in Chronic Kidney Disease. Seminars in nephrology Unruh, M. n., Tamura, M. K. 2015; 35 (4): 303

  View details for PubMedID 26355248

• Cognitive Function in Adults Aging with Fabry Disease: A Case-Control Feasibility Study Using Telephone-Based Assessments JIMD REPORTS, VOL 18 Wadley, V. G., McClure, L. A., Warnock, D. G., Lassen-Greene, C. L., Hopkin, R. J., Laney, D. A., Clarke, V. M., Tamura, M., Howard, G., Sims, K., Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters 2015; 18: 41-50

  Abstract

  We examined the feasibility of recruiting US adults ≥45 years old with Fabry disease (FD) for telephone assessments of cognitive functioning. A case-control design matched each FD participant on age, sex, race, and education to four participants from a population-based study. Fifty-four participants with FD age 46-72 years were matched to 216 controls. Standardized cognitive assessments, quality of life (QOL), and medical histories were obtained by phone, supplemented by objective indices of comorbidities. Normalized scores on six cognitive tasks were calculated. On the individual tasks, scores on list recall and semantic fluency were significantly lower among FD participants (p-values < 0.05), while scores on the other four tasks did not differ. After averaging each participant's normalized scores to form a cognitive composite, we examined group differences in composite scores, before and after adjusting for multiple covariates using generalized estimating equations. The composite scores of FD cases were marginally lower than controls before covariate adjustments (p = 0.08). QOL and mental health variables substantially attenuated this finding (p = 0.75), highlighting the influence of these factors on cognition in FD. Additional adjustment for cardiovascular comorbidities, kidney function, and stroke had negligible impact, despite higher prevalence in the FD sample. Telephone-based cognitive assessment methods are feasible among adults with FD, affording access to a geographically dispersed sample. Although decrements in discrete cognitive domains were observed, the overall cognitive function of older adults with FD was equivalent to that of well-matched controls before and after accounting for multiple confounding variables.

  View details for DOI 10.1007/8904_2014_346

  View details for Web of Science ID 000376981500005

  View details for PubMedID 25567791

  View details for PubMedCentralID PMC4361921

• Nondisease-Specific Problems and All-Cause Mortality among Older Adults with CKD: The REGARDS Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Bowling, C. B., Booth, J. N., Gutierrez, O. M., Tamura, M. K., Huang, L., Kilgore, M., Judd, S., Warnock, D. G., McClellan, W. M., Allman, R. M., Muntner, P. 2014; 9 (10): 1737-1745

  Abstract

  The term "nondisease-specific" has been used to describe problems that cross multiple domains of health and are not necessarily the result of a single underlying disease. Although individuals with reduced eGFR and elevated albumin-to-creatinine ratio have many comorbidities, the prevalence of and outcomes associated with nondisease-specific problems have not been well studied.Participants included 3557 black and white United States adults ≥75 years of age from the Reasons for Geographic and Racial Differences in Stroke Study. Nondisease-specific problems included cognitive impairment, depressive symptoms, exhaustion, falls, impaired mobility, and polypharmacy. Hazard ratios for mortality over a median (interquartile range) of 5.4 (4.2-6.9) years of follow-up associated with one, two, or three to six nondisease-specific problems were calculated and stratified by eGFR (≥60, 45-59, and <45 ml/min per 1.73 m(2)) and separately, albumin-to-creatinine ratio (<30, 30-299, and ≥300 mg/g). Secondary outcomes included hospitalizations and emergency department visits over 1.8 (0.7-4.0) and 2.3 (0.9-4.7) years of follow-up, respectively.The prevalence of nondisease-specific problems was more common at lower eGFR and higher albumin-to-creatinine ratio levels. Within each eGFR and albumin-to-creatinine ratio strata, the risk for mortality was higher among those with a greater number of nondisease-specific problems. For example, among those with an eGFR=45-59 ml/min per 1.73 m(2), the multivariable adjusted hazard ratios (95% confidence intervals) for mortality associated with one, two, or three to six nondisease-specific problems were 1.17 (0.78 to 1.76), 1.95 (1.24 to 3.07), and 2.44 (1.39 to 4.27; P trend <0.001). Risk for hospitalization and emergency department visits was higher among those with more nondisease-specific problems within eGFR and albumin-to-creatinine ratio strata.Among older adults, nondisease-specific problems commonly co-occur with reduced eGFR and elevated albumin-to-creatinine ratio. Identification of nondisease-specific problems may provide mortality risk information independent of measures of kidney function.

  View details for DOI 10.2215/CJN.00880114

  View details for Web of Science ID 000342713100011

  View details for PubMedID 25278551

  View details for PubMedCentralID PMC4186504

• Performance of the NINDS-CSN 5-Minute Protocol in a National Population-Based Sample JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY Kennedy, R. E., Wadley, V. G., McClure, L. A., Letter, A. J., Unverzagt, F. W., Crowe, M., Nyenhius, D., Kelley, B. J., Kana, B., Marceaux, J., Tamura, M. K., Howard, V., Howard, G. 2014; 20 (8): 856-867

  Abstract

  In 2006, the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) Vascular Cognitive Impairment Harmonization Standards recommended a 5-Minute Protocol as a brief screening instrument for vascular cognitive impairment (VCI). We report demographically adjusted norms for the 5-Minute Protocol and its relation to other measures of cognitive function and cerebrovascular risk factors. We performed a cross-sectional analysis of 7199 stroke-free adults in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study on the NINDS-CSN 5-Minute Protocol score. Total scores on the 5-Minute Protocol were inversely correlated with age and positively correlated with years of education, and performance on the Six-Item Screener, Word List Learning, and Animal Fluency (all p-values <.001). Higher cerebrovascular risk on the Framingham Stroke Risk Profile (FSRP) was associated with lower total 5-Minute Protocol scores (p <.001). The 5-Minute Protocol also differentiated between participants with and without confirmed stroke and with and without stroke symptom histories (p <.001). The NINDS-CSN 5-Minute Protocol is a brief, easily administered screening measure that is sensitive to cerebrovascular risk and offers a valid method of screening for cognitive impairment in populations at risk for VCI.

  View details for DOI 10.1017/S1355617714000733

  View details for Web of Science ID 000344951500009

  View details for PubMedCentralID PMC4452126

• Higher Levels of Cystatin C Are Associated with Worse Cognitive Function in Older Adults with Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort Cognitive Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Yaffe, K., Kurella-Tamura, M., Ackerson, L., Hoang, T. D., Anderson, A. H., Duckworth, M., Go, A. S., Krousel-Wood, M., Kusek, J. W., Lash, J. P., Ojo, A., Robinson, N., Sehgal, A. R., Sondheimer, J. H., Steigerwalt, S., Townsend, R. R., CRIC Study Investigators 2014; 62 (9): 1623-1629

  Abstract

  To determine the association between cognition and levels of cystatin C in persons with chronic kidney disease (CKD).Prospective observational study.Chronic Renal Insufficiency Cohort Cognitive Study.Individuals with a baseline cognitive assessment completed at the same visit as serum cystatin C measurement (N = 821; mean age 64.9, 50.6% male, 48.6% white).Levels of serum cystatin C were categorized into tertiles; cognitive function was assessed using six neuropsychological tests. Scores on these tests were compared across tertiles of cystatin C using linear regression and logistic regression to examine the association between cystatin C level and cognitive performance (1 standard deviation difference from the mean).After multivariable adjustment for age, race, education, and medical comorbidities in linear models, higher levels of cystatin C were associated with worse cognition on the modified Mini-Mental State Examination, Buschke Delayed Recall, Trail-Making Test Part (Trails) A and Part B, and Boston Naming (P < .05 for all). This association remained statistically significant for Buschke Delayed Recall (P = .01) and Trails A (P = .03) after additional adjustment for estimated glomerular filtration rate (eGFR). The highest tertile of cystatin C was associated with greater likelihood of poor performance on Trails A (odds ratio (OR) = 2.17, 95% confidence interval (CI) = 1.16-4.06), Trails B (OR = 1.89, 95% CI = 1.09-3.27), and Boston Naming (OR = 1.85, 95% CI = 1.07-3.19) than the lowest tertile after multivariate adjustment in logistic models.In individuals with CKD, higher serum cystatin C levels were associated with worse cognition and greater likelihood of poor cognitive performance on attention, executive function, and naming. Cystatin C is a marker of cognitive impairment and may be associated with cognition independent of eGFR.

  View details for DOI 10.1111/jgs.12986

  View details for Web of Science ID 000342722900001

  View details for PubMedID 25125225

  View details for PubMedCentralID PMC4201363

• Prognostic stratification in older adults commencing dialysis. journals of gerontology. Series A, Biological sciences and medical sciences Cheung, K. L., Montez-Rath, M. E., Chertow, G. M., Winkelmayer, W. C., Periyakoil, V. S., Kurella Tamura, M. 2014; 69 (8): 1033-1039

  Abstract

  Accurate prognostic models could inform treatment decisions for older adults with end-stage renal disease who are considering dialysis and might identify patients more appropriate for conservative care or hospice.In a cohort of patients aged ≥67 years commencing dialysis in the United States between January 1, 2008 and June 30, 2009, we compared the discrimination of three existing instruments (the Liu index; the French Renal Epidemiology and Information Network score; and hospice eligibility criteria) for the prediction of 6-month mortality. We estimated the odds of death associated with each prognostic index using logistic regression with and without adjustment for age. Predictive indices were compared using the concordance ("c")-statistic.Of 44,109 eligible patients, 10,289 (23.3%) died within 6 months of dialysis initiation. The c-statistic for the Liu, Renal Epidemiology and Information Network, hospice eligibility criteria, and combined Liu/hospice eligibility criteria scores without and with age were 0.62/0.65, 0.63/0.66, 0.65/0.68, and 0.68/0.70, respectively. Discrimination was poorer at older ages, especially for the Liu and Renal Epidemiology and Information Network scores. Although sensitivity was poor, a Renal Epidemiology and Information Network score ≥9 or an hospice eligibility criteria ≥3 had relatively high specificity.Existing prognostic indices based on administrative data perform poorly with respect to prediction of 6-month mortality in older patients with end-stage renal disease commencing dialysis.

  View details for DOI 10.1093/gerona/glt289

  View details for PubMedID 24482541

• A Patient-Centered Vision of Care for ESRD: Dialysis as a Bridging Treatment or as a Final Destination? JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Vandecasteele, S. J., Tamura, M. 2014; 25 (8): 1647-1651

  Abstract

  The ESRD population is heterogeneous, including patients without severe comorbidity for whom dialysis is a bridge to transplantation or a long-term maintenance treatment, as well as patients with a limited life expectancy as a result of advanced age or severe comorbidity for whom dialysis will be the final treatment destination. The complex medical and social context of this latter group fits poorly in the homogeneous, disease-centered, and process-driven approach of many clinical practice guidelines for dialysis. In this commentary, we argue that the standards of treatment allocated to each individual patient should be defined not merely by his or her disease state, but also by his or her preferences and prognosis. In this more patient-centered approach, three attainable treatment goals with a corresponding therapeutic approach could be defined: (1) dialysis as bridging or long-term maintenance treatment, (2) dialysis as final treatment destination, and (3) active medical management without dialysis. For patients with a better overall prognosis, this approach will emphasize complication prevention and long-term survival. For patients with a limited overall prognosis, strictly disease-centered interventions often impose a treatment burden that does not translate into a proportional improvement in quantity or quality of life. For these patients, a patient-centered approach will place more emphasis on palliative management strategies that are less disease specific.

  View details for DOI 10.1681/ASN.2013101082

  View details for Web of Science ID 000339686400008

  View details for PubMedID 24833125

  View details for PubMedCentralID PMC4116069

• Thematic Synthesis of Qualitative Studies on Patient and Caregiver Perspectives on End-of-Life Care in CKD AMERICAN JOURNAL OF KIDNEY DISEASES Tong, A., Cheung, K. L., Nair, S. S., Tamura, M. K., Craig, J. C., Winkelmayer, W. C. 2014; 63 (6): 913-927

  Abstract

  Although dialysis prolongs life for patients with end-stage kidney disease, 20% of deaths in this population are preceded by dialysis therapy withdrawal. Recently, there has been more focus on conservative (nondialytic) care as a legitimate option, particularly for elderly patients. This study aims to describe patients' and caregivers' perspectives on conservative treatment and end-of-life care in chronic kidney disease (CKD).Systematic review and thematic synthesis of qualitative studies.Patients with CKD and caregivers.MEDLINE, Embase, PsycINFO, CINAHL, and reference lists were searched to May 2013.Thematic synthesis was used to analyze the findings.26 studies involving more than 711 patients (non-dialysis dependent [n=41], hemodialysis [n=544], peritoneal dialysis [n=9]; unspecified dialysis modality [n=31], conservative management [n=86]) and 178 caregivers were included. We identified 5 themes: invasive suffering (bodily deterioration, loss of freedom and independence, unyielding fatigue and pain, resignation, treatment burden and harm, financial strain), personal vulnerability (imminence of death, misunderstanding and judgment, autonomy and dignity, medical abandonment, trust and safety), relational responsibility (being a burden, demonstrating loyalty, protecting others from grief), negotiating existential tensions (accepting natural course of life, disrupted aging, worthlessness, living on borrowed time, respecting sanctity of life, life satisfaction, preserving self-identity), and preparedness (decisional clarity, informational power, spirituality and hope).Non-English articles were excluded; therefore, the transferability of findings to other populations is unclear.Some patients with CKD experience physical and psychosocial frailty and feel ambivalent about prolonging life. Some caregivers believe in providing relief from suffering, but are uncertain about making decisions regarding dialysis therapy initiation and discontinuation. We suggest that CKD management should encompass palliative care strategies that promote emotional resilience, sense of well-being, and self-value. Also, respectful and attentive communication may empower patients to convey their values and preferences about their own care.

  View details for DOI 10.1053/j.ajkd.2013.11.017

  View details for Web of Science ID 000336385900009

  View details for PubMedID 24411716

• State medicaid coverage, ESRD incidence, and access to care. Journal of the American Society of Nephrology Kurella-Tamura, M., Goldstein, B. A., Hall, Y. N., Mitani, A. A., Winkelmayer, W. C. 2014; 25 (6): 1321-1329

  Abstract

  The proportion of low-income nonelderly adults covered by Medicaid varies widely by state. We sought to determine whether broader state Medicaid coverage, defined as the proportion of each state's low-income nonelderly adult population covered by Medicaid, associates with lower state-level incidence of ESRD and greater access to care. The main outcomes were incidence of ESRD and five indicators of access to care. We identified 408,535 adults aged 20-64 years, who developed ESRD between January 1, 2001, and December 31, 2008. Medicaid coverage among low-income nonelderly adults ranged from 12.2% to 66.0% (median 32.5%). For each additional 10% of the low-income nonelderly population covered by Medicaid, there was a 1.8% (95% confidence interval, 1.0% to 2.6%) decrease in ESRD incidence. Among nonelderly adults with ESRD, gaps in access to care between those with private insurance and those with Medicaid were narrower in states with broader coverage. For a 50-year-old white woman, the access gap to the kidney transplant waiting list between Medicaid and private insurance decreased by 7.7 percentage points in high (>45%) versus low (<25%) Medicaid coverage states. Similarly, the access gap to transplantation decreased by 4.0 percentage points and the access gap to peritoneal dialysis decreased by 3.8 percentage points in high Medicaid coverage states. In conclusion, states with broader Medicaid coverage had a lower incidence of ESRD and smaller insurance-related access gaps.

  View details for DOI 10.1681/ASN.2013060658

  View details for PubMedID 24652791

• Effects of Frequent Hemodialysis on Perceived Caregiver Burden in the Frequent Hemodialysis Network Trials CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Suri, R. S., Larive, B., Hall, Y., Kimmel, P. L., Kliger, A. S., Levin, N., Tamura, M. K., Chertow, G. M. 2014; 9 (5): 936-942

  Abstract

  Patients receiving hemodialysis often perceive their caregivers are overburdened. We hypothesize that increasing hemodialysis frequency would result in higher patient perceptions of burden on their unpaid caregivers.In two separate trials, 245 patients were randomized to receive in-center daily hemodialysis (6 days/week) or conventional hemodialysis (3 days/week) while 87 patients were randomized to receive home nocturnal hemodialysis (6 nights/week) or home conventional hemodialysis for 12 months. Changes in overall mean scores over time in the 10-question Cousineau perceived burden scale were compared.In total, 173 of 245 (70%) and 80 of 87 (92%) randomized patients in the Daily and Nocturnal Trials, respectively, reported having an unpaid caregiver at baseline or during follow-up. Relative to in-center conventional dialysis, the 12-month change in mean perceived burden score with in-center daily hemodialysis was -2.1 (95% confidence interval, -9.4 to +5.3; P=0.58). Relative to home conventional dialysis, the 12-month change in mean perceived burden score with home nocturnal dialysis was +6.1 (95% confidence interval, -0.8 to +13.1; P=0.08). After multiple imputation for missing data in the Nocturnal Trial, the relative difference between home nocturnal and home conventional hemodialysis was +9.4 (95% confidence interval, +0.55 to +18.3; P=0.04). In the Nocturnal Trial, changes in perceived burden were inversely correlated with adherence to dialysis treatments (Pearson r=-0.35; P=0.02).Relative to conventional hemodialysis, in-center daily hemodialysis did not result in higher perceptions of caregiver burden. There was a trend to higher perceived caregiver burden among patients randomized to home nocturnal hemodialysis. These findings may have implications for the adoption of and adherence to frequent nocturnal hemodialysis.

  View details for DOI 10.2215/CJN.07170713

  View details for Web of Science ID 000335519300017

  View details for PubMedID 24721892

  View details for PubMedCentralID PMC4011443

• KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for the Evaluation and Management of CKD AMERICAN JOURNAL OF KIDNEY DISEASES Inker, L. A., Astor, B. C., Fox, C. H., Isakova, T., Lash, J. P., Peralta, C. A., Tamura, M., Feldman, H. I., Rocco, M. V., Berns, J. S. 2014; 63 (5): 713–35

  Abstract

  The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) guideline for evaluation, classification, and stratification of chronic kidney disease (CKD) was published in 2002. The KDOQI guideline was well accepted by the medical and public health communities, but concerns and criticisms arose as new evidence became available since the publication of the original guidelines. KDIGO (Kidney Disease: Improving Global Outcomes) recently published an updated guideline to clarify the definition and classification of CKD and to update recommendations for the evaluation and management of individuals with CKD based on new evidence published since 2002. The primary recommendations were to retain the current definition of CKD based on decreased glomerular filtration rate or markers of kidney damage for 3 months or more and to include the cause of kidney disease and level of albuminuria, as well as level of glomerular filtration rate, for CKD classification. NKF-KDOQI convened a work group to write a commentary on the KDIGO guideline in order to assist US practitioners in interpreting the KDIGO guideline and determining its applicability within their own practices. Overall, the commentary work group agreed with most of the recommendations contained in the KDIGO guidelines, particularly the recommendations regarding the definition and classification of CKD. However, there were some concerns about incorporating the cause of disease into CKD classification, in addition to certain recommendations for evaluation and management.

  View details for PubMedID 24647050

• Does chronic kidney disease affect outcomes after major abdominal surgery? Results from the national surgical quality improvement program. Journal of gastrointestinal surgery Cloyd, J. M., Ma, Y., Morton, J. M., Kurella Tamura, M., Poultsides, G. A., Visser, B. C. 2014; 18 (3): 605-612

  Abstract

  The impact of chronic kidney disease (CKD) and end-stage renal disease on outcomes following major abdominal surgery is not well defined.The 2008 NSQIP database was queried to identify adult patients undergoing complex abdominal surgery (major colorectal, hepatobiliary, pancreatic, gastric, and esophageal operations). Thirty-day morbidity and mortality in patients on hemodialysis (HD) versus patients not on HD were compared. The impact of preoperative renal insufficiency, measured by glomerular filtration rate (GFR), on morbidity and mortality was then assessed in non-dialysis patients.Of 24,572 patients who underwent major abdominal operations, excluding emergency cases, only 149 (0.6 %) were on HD preoperatively. Thirty-day mortality in the HD group was 12.8 % compared to 1.8 % for those not on HD (p < 0.0001). Overall complication rate was 23.5 versus 12.3 % (p < 0.0001). In particular, rates of pneumonia (6.7 vs 3.0 %, p < 0.05) and sepsis (12.8 vs 5.3 %, p < 0.001) were higher in patients on HD. In patients not on HD, GFR was significantly predictive of postoperative mortality after controlling for age, gender, race, emergency status, and comorbidities. Compared to patients with normal preoperative kidney function (GFR, 75-90 ml/min/1.73 m(2)), even modest CKD (GFR, 45-60 ml/min/1.73 m(2)) was associated with increased postoperative mortality (odds ratio (OR), 1.62). With greater impairment in kidney function, postoperative mortality was even more marked (GFR, 30-45 ml/min/1.73 m(2) and OR, 2.84; GFR, 15-30 ml/min/1.73 m(2) and OR, 5.56). In addition, CKD was independently associated with increased postoperative complications.Any degree of preoperative kidney impairment, even mild asymptomatic disease, is associated with clinically significant increases in 30-day postoperative morbidity and mortality following major abdominal surgery.

  View details for DOI 10.1007/s11605-013-2390-3

  View details for PubMedID 24241964

• Aging and Chronic Kidney Disease: The Impact on Physical Function and Cognition JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Anand, S., Johansen, K. L., Tamura, M. K. 2014; 69 (3): 315-322

  Abstract

  Evidence has recently been building that the presence of chronic kidney disease (CKD) is an independent contributor to decline in physical and cognitive functions in older adults. CKD affects 45% of persons older than 70 years of age and can double the risk for physical impairment, cognitive dysfunction, and frailty. To increase awareness of this relatively new concept of CKD as a risk factor for accelerated aging, we review studies on the association of CKD with physical function, frailty, and cognitive function. We also present a summary of the proposed mechanisms for these associations.

  View details for DOI 10.1093/gerona/glt109

  View details for Web of Science ID 000333384800011

• Interpreting Treatment Effects From Clinical Trials in the Context of Real-World Risk Information End-Stage Renal Disease Prevention in Older Adults JAMA INTERNAL MEDICINE O'Hare, A. M., Hotchkiss, J. R., Tamura, M. K., Larson, E. B., Hemmelgarn, B. R., Batten, A., Covinsky, K. E. 2014; 174 (3): 391-397

  Abstract

  Older adults are often excluded from clinical trials. The benefit of preventive interventions tested in younger trial populations may be reduced when applied to older adults in the clinical setting if they are less likely to survive long enough to experience those outcomes targeted by the intervention.To extrapolate a treatment effect similar to those reported in major randomized clinical trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of end-stage renal disease (ESRD) to a real-world population of older patients with chronic kidney disease.Simulation study in a retrospective cohort conducted in Department of Veterans Affairs medical centers. We included 371 470 patients 70 years or older with chronic kidney disease.Level of estimated glomerular filtration rate (eGFR) and proteinuria.Among members of this cohort, we evaluated the expected effect of a 30% reduction in relative risk on the number needed to treat (NNT) to prevent 1 case of ESRD over a 3-year period. These limits were selected to mimic the treatment effect achieved in major trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of ESRD. These trials have reported relative risk reductions of 23% to 56% during observation periods of 2.6 to 3.4 years, yielding NNTs to prevent 1 case of ESRD of 9 to 25.The NNT to prevent 1 case of ESRD among members of this cohort ranged from 16 in patients with the highest baseline risk (eGFR of 15-29 mL/min/1.73 m(2) with a dipstick proteinuria measurement of ≥ 2+) to 2500 for those with the lowest baseline risk (eGFR of 45-59 mL/min/1.73 m(2) with negative or trace proteinuria and eGFR of ≥ 60 mL/min/1.73 m2 with dipstick proteinuria measurement of 1+). Most patients belonged to groups with an NNT of more than 100, even when the exposure time was extended over 10 years and in all sensitivity analyses.Differences in baseline risk and life expectancy between trial subjects and real-world populations of older adults with CKD may reduce the marginal benefit to individual patients of interventions to prevent ESRD.

  View details for DOI 10.1001/jamainternmed.2013.13328

  View details for Web of Science ID 000333052100019

  View details for PubMedID 24424348

  View details for PubMedCentralID PMC4119007

• Educational programs improve the preparation for dialysis and survival of patients with chronic kidney disease KIDNEY INTERNATIONAL Tamura, M. K., Li, S., Chen, S., Cavanaugh, K. L., Whaley-Connell, A. T., McCullough, P. A., Mehrotra, R. L. 2014; 85 (3): 686-692

  Abstract

  Preparation for end-stage renal disease (ESRD) is widely acknowledged to be suboptimal in the United States. We sought to determine whether participation in a kidney disease screening and education program resulted in improved ESRD preparation and survival in 595 adults who developed ESRD after participating in the National Kidney Foundation Kidney Early Evaluation Program (KEEP), a community-based screening and education program. Non-KEEP patients were selected from a national ESRD registry and matched to KEEP participants based on demographic and clinical characteristics. The main outcomes were pre-ESRD nephrologist care, placement of permanent vascular access, use of peritoneal dialysis, pre-emptive transplant wait listing, transplantation, and mortality after ESRD. Participation in KEEP was associated with significantly higher rates of pre-ESRD nephrologist care (76.0% vs. 69.3%), peritoneal dialysis (10.3% vs. 6.4%), pre-emptive transplant wait listing (24.2% vs. 17.1%), and transplantation (9.7% vs. 6.4%) but not with higher rates of permanent vascular access (23.4% vs. 20.1%). Participation in KEEP was associated with a lower risk for mortality (hazard ratio 0.80), but this was not statistically significant after adjusting for ESRD preparation. Thus, participation in a voluntary community kidney disease screening and education program was associated with higher rates of ESRD preparation and survival.

  View details for DOI 10.1038/ki.2013.369

  View details for Web of Science ID 000332225600028

  View details for PubMedID 24067435

• Aging and chronic kidney disease: the impact on physical function and cognition. journals of gerontology. Series A, Biological sciences and medical sciences Anand, S., Johansen, K. L., Kurella Tamura, M. 2014; 69 (3): 315-322

  Abstract

  Evidence has recently been building that the presence of chronic kidney disease (CKD) is an independent contributor to decline in physical and cognitive functions in older adults. CKD affects 45% of persons older than 70 years of age and can double the risk for physical impairment, cognitive dysfunction, and frailty. To increase awareness of this relatively new concept of CKD as a risk factor for accelerated aging, we review studies on the association of CKD with physical function, frailty, and cognitive function. We also present a summary of the proposed mechanisms for these associations.

  View details for DOI 10.1093/gerona/glt109

  View details for PubMedID 23913934

• Spontaneous BOLD Signal Fluctuations in Young Healthy Subjects and Elderly Patients with Chronic Kidney Disease. PloS one Jahanian, H., Ni, W. W., Christen, T., Moseley, M. E., Kurella Tamura, M., Zaharchuk, G. 2014; 9 (3)

  View details for DOI 10.1371/journal.pone.0092539

  View details for PubMedID 24651703

• Spontaneous BOLD signal fluctuations in young healthy subjects and elderly patients with chronic kidney disease. PloS one Jahanian, H., Ni, W. W., Christen, T., Moseley, M. E., Kurella Tamura, M., Zaharchuk, G. 2014; 9 (3)

  Abstract

  Spontaneous fluctuations in blood oxygenation level-dependent (BOLD) images are the basis of resting-state fMRI and frequently used for functional connectivity studies. However, there may be intrinsic information in the amplitudes of these fluctuations. We investigated the possibility of using the amplitude of spontaneous BOLD signal fluctuations as a biomarker for cerebral vasomotor reactivity. We compared the coefficient of variation (CV) of the time series (defined as the temporal standard deviation of the time series divided by the mean signal intensity) in two populations: 1) Ten young healthy adults and 2) Ten hypertensive elderly subjects with chronic kidney disease (CKD). We found a statistically significant increase (P<0.01) in the CV values for the CKD patients compared with the young healthy adults in both gray matter (GM) and white matter (WM). The difference was independent of the exact segmentation method, became more significant after correcting for physiological signals using RETROICOR, and mainly arose from very low frequency components of the BOLD signal fluctuation (f<0.025 Hz). Furthermore, there was a strong relationship between WM and GM signal fluctuation CV's (R2 = 0.87) in individuals, with a ratio of about 1∶3. These results suggest that amplitude of the spontaneous BOLD signal fluctuations may be used to assess the cerebrovascular reactivity mechanisms and provide valuable information about variations with age and different disease states.

  View details for DOI 10.1371/journal.pone.0092539

  View details for PubMedID 24651703

  View details for PubMedCentralID PMC3961376

• Vitamin d deficiency and mortality in patients receiving dialysis: the comprehensive dialysis study. Journal of renal nutrition Anand, S., Chertow, G. M., Johansen, K. L., Grimes, B., Dalrymple, L. S., Kaysen, G. A., Kurella Tamura, M. 2013; 23 (6): 422-427

  Abstract

  Although several studies have shown poorer survival among individuals with 25-hydroxy (OH) vitamin D deficiency, data on patients receiving dialysis are limited. Using data from the Comprehensive Dialysis Study (CDS), we tested the hypothesis that patients new to dialysis with low serum concentrations of 25-OH vitamin D would experience higher mortality and hospitalizations.The CDS is a prospective cohort study.We recruited participants from 56 dialysis units located throughout the United States.We obtained data on demographics, comorbidites, and laboratory values from the CDS Patient Questionnaire as well as the Medical Evidence Form (CMS form 2728). Participants provided baseline serum samples for 25-OH vitamin D measurements.We ascertained time to death and first hospitalization as well as number of first-year hospitalizations via the U.S. Renal Data System standard analysis files. We used Cox proportional hazards to determine the association between 25-OH vitamin D tertiles and survival and hospitalization. For number of hospitalizations in the first year, we used negative binomial regression.The analytic cohort was composed of 256 patients with Patient Questionnaire data and 25-OH vitamin D concentrations. The mean age of participants was 62 (±14.0) years, and mean follow-up was 3.8 years. Patients with 25-OH vitamin D concentrations in the lowest tertile (<10.6 ng/mL) at the start of dialysis experienced higher mortality (adjusted hazard ratio 1.75, 95% confidence interval [CI] 1.03-2.97) as well as hospitalization (adjusted hazard ratio 1.76, 95% CI 1.24-2.49). Patients in the lower 2 tertiles (<15.5 ng/mL) experienced a higher rate of hospitalizations in the first year (incidence rate ratio 1.70 [95% CI 1.06-2.72] for middle tertile, 1.66 [95% CI 1.10-2.51] for lowest tertile).We found a sizeable increase in mortality and hospitalization for patients on dialysis with severe 25-OH vitamin D deficiency.

  View details for DOI 10.1053/j.jrn.2013.05.003

  View details for PubMedID 23876600

• The patient perspective and physician's role in making decisions on instituting dialysis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Kurella Tamura, M., Periyakoil, V. S. 2013; 28 (11): 2663-2666

  View details for DOI 10.1093/ndt/gft379

  View details for PubMedID 24009286

  View details for PubMedCentralID PMC3811061

• Vitamin D Deficiency and Mortality in Patients Receiving Dialysis: The Comprehensive Dialysis Study JOURNAL OF RENAL NUTRITION Anand, S., Chertow, G. M., Johansen, K. L., Grimes, B., Dalrymple, L. S., Kaysen, G. A., Tamura, M. K. 2013; 23 (6): 422-427

  Abstract

  Although several studies have shown poorer survival among individuals with 25-hydroxy (OH) vitamin D deficiency, data on patients receiving dialysis are limited. Using data from the Comprehensive Dialysis Study (CDS), we tested the hypothesis that patients new to dialysis with low serum concentrations of 25-OH vitamin D would experience higher mortality and hospitalizations.The CDS is a prospective cohort study.We recruited participants from 56 dialysis units located throughout the United States.We obtained data on demographics, comorbidites, and laboratory values from the CDS Patient Questionnaire as well as the Medical Evidence Form (CMS form 2728). Participants provided baseline serum samples for 25-OH vitamin D measurements.We ascertained time to death and first hospitalization as well as number of first-year hospitalizations via the U.S. Renal Data System standard analysis files. We used Cox proportional hazards to determine the association between 25-OH vitamin D tertiles and survival and hospitalization. For number of hospitalizations in the first year, we used negative binomial regression.The analytic cohort was composed of 256 patients with Patient Questionnaire data and 25-OH vitamin D concentrations. The mean age of participants was 62 (±14.0) years, and mean follow-up was 3.8 years. Patients with 25-OH vitamin D concentrations in the lowest tertile (<10.6 ng/mL) at the start of dialysis experienced higher mortality (adjusted hazard ratio 1.75, 95% confidence interval [CI] 1.03-2.97) as well as hospitalization (adjusted hazard ratio 1.76, 95% CI 1.24-2.49). Patients in the lower 2 tertiles (<15.5 ng/mL) experienced a higher rate of hospitalizations in the first year (incidence rate ratio 1.70 [95% CI 1.06-2.72] for middle tertile, 1.66 [95% CI 1.10-2.51] for lowest tertile).We found a sizeable increase in mortality and hospitalization for patients on dialysis with severe 25-OH vitamin D deficiency.

  View details for DOI 10.1053/j.jrn.2013.05.003

  View details for Web of Science ID 000327007600007

• Frailty and Dialysis Initiation SEMINARS IN DIALYSIS Johansen, K. L., Delgado, C., Bao, Y., Tamura, M. K. 2013; 26 (6): 690-696

  Abstract

  Frailty is a physiologic state of increased vulnerability to stressors that results from decreased physiologic reserves or dysregulation of multiple physiologic systems. The construct of frailty has been operationalized as a composite of poor physical function, exhaustion, low physical activity, and weight loss. Several studies have now examined the prevalence of frailty among chronic kidney disease (CKD) or end-stage renal disease (ESRD) patients and have found frailty to be more common among individuals with CKD than among those without. Furthermore, frailty is associated with adverse outcomes among incident dialysis patients, including higher risk of hospitalization and death. Recent evidence shows that frail patients are started on dialysis earlier (at a higher estimated glomerular filtration rate [eGFR]) on average than nonfrail patients, but it remains unclear whether these patients' frailty is a result of uremia or is independent of CKD. The survival disadvantage that has been associated with early initiation of dialysis in observational studies could be mediated in part through confounding on the basis of unmeasured frailty. However, available data do not suggest improvement in frailty upon initiation of dialysis; rather, the trajectory appears to be toward higher levels of dependence in activities of daily living (ADLs) after dialysis initiation. Overall, there are no data to suggest that frail patients derive any benefit from early initiation of dialysis either in the form of improved survival or functional status.

  View details for DOI 10.1111/sdi.12126

  View details for Web of Science ID 000327030200010

  View details for PubMedID 24004376

  View details for PubMedCentralID PMC3984466

• Pre-ESRD Changes in Body Weight and Survival in Nursing Home Residents Starting Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Stack, S., Chertow, G. M., Johansen, K. L., Si, Y., Tamura, M. K. 2013; 8 (10): 1734-1740

  Abstract

  Among patients receiving maintenance dialysis, weight loss at any body mass index is associated with mortality. However, it is not known whether weight changes before dialysis initiation are associated with mortality and if so, what risks are associated with weight gain or loss.Linking data from the US Renal Data System to a national registry of nursing home residents, this study identified 11,090 patients who started dialysis between January of 2000 and December of 2006. Patients were categorized according to weight measured between 3 and 6 months before dialysis initiation and the percentage change in body weight before dialysis initiation (divided into quintiles). The outcome was mortality within 1 year of starting dialysis.There were 361 patients (3.3%) who were underweight (Quételet's [body mass] index<18.5 kg/m(2)) and 4046 patients (36.5%) who were obese (body mass index ≥ 30 kg/m(2)) before dialysis initiation. The median percentage change in body weight before dialysis initiation was -6% (interquartile range=-13% to 1%). There were 6063 deaths (54.7%) over 1 year of follow-up. Compared with patients with minimal weight changes (-3% to 3%, quintile 4), patients with weight loss ≥ 15% (quintile 1) had 35% higher risk for mortality (95% confidence interval, 1.25 to 1.47), whereas those patients with weight gain ≥ 4% (quintile 5) had a 24% higher risk for mortality (95% confidence interval, 1.14 to 1.35) adjusted for baseline body mass index and other confounders.Among nursing home residents, changes in body weight in advance of dialysis initiation are associated with significantly higher 1-year mortality.

  View details for DOI 10.2215/CJN.01410213

  View details for PubMedID 24009221

• Five Policies to Promote Palliative Care for Patients with ESRD CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Meier, D. E. 2013; 8 (10): 1783-1790

  Abstract

  Patients with ESRD experience complex and costly care that does not always meet their needs. Palliative care, which focuses on improving quality of life and relieving suffering for patients with serious illnesses, could address a large unmet need among patients with ESRD. Strengthening palliative care is a top policy priority for health reform efforts based on strong evidence that palliative care improves value. This commentary outlines palliative care policies for patients with ESRD and is directed at policymakers, dialysis providers, nephrology professional societies, accreditation organizations, and funding agencies who play a key role in the delivery and determination of quality of ESRD care. Herein we suggest policies to promote palliative care for patients with ESRD by addressing key barriers, including the lack of access to palliative care, lack of capacity to deliver palliative care, and a limited evidence base. We also provide examples of how these policies could be implemented within the existing ESRD care infrastructure.

  View details for DOI 10.2215/CJN.02180213

  View details for Web of Science ID 000325268200021

  View details for PubMedID 23744000

  View details for PubMedCentralID PMC3789338

• Impact of frequent hemodialysis on anemia management: results from the Frequent Hemodialysis Network (FHN) Trials NEPHROLOGY DIALYSIS TRANSPLANTATION Ornt, D. B., Larive, B., Rastogi, A., Rashid, M., Daugirdas, J. T., Hernandez, A., Tamura, M. K., Suri, R. S., Levin, N. W., Kliger, A. S. 2013; 28 (7): 1888-1898

  Abstract

  The extent to which anemia management is facilitated by more frequent hemodialysis (HD) is controversial. We hypothesized as a preselected outcome that patients receiving HD six times (6×) compared with three times (3×) per week would require lower doses of erythropoietin-stimulating agents (ESA) and/or achieve higher blood hemoglobin (Hb) concentrations.Subjects enrolled in the Frequent Hemodialysis Network (FHN) daily and nocturnal trials were studied. As the primary outcome for anemia, the dose of ESAs was recorded at 4-month intervals and the monthly dose of intravenous iron (IV Fe) was reported. Serum iron, transferrin saturation and ferritin were measured at baseline and then at 4-month intervals, whereas Hb concentration was measured monthly.There was no significant treatment effect in the 6× versus 3× treatment groups on logESA dose or the ratio of log of ESA dose to Hb concentration in either trial. In the daily trial, Hb concentrations increased significantly in the 6× versus 3× group, at Month 12 compared with baseline (0.3 g/dL; 95% CI: 0.05-0.58, P<0.021), but both groups had Hb concentrations in the usual target range. In the daily trial, the weekly logESA dose and the logESA dose to Hb concentration ratio tended to decline more in the 6× versus 3× group. This trend was not observed in the nocturnal trial. IV Fe doses were significantly lower in the 6× compared with the 3× group by Month 12 in the nocturnal trial, but not different in the daily trial.In the FHN Daily and Nocturnal Trials, more frequent HD did not have a significant or clinically important effect on anemia management.

  View details for DOI 10.1093/ndt/gfs593

  View details for Web of Science ID 000321821900034

  View details for PubMedCentralID PMC3707527

• Risk Factors for ESRD in Individuals With Preserved Estimated GFR With and Without Albuminuria: Results From the Kidney Early Evaluation Program (KEEP) AMERICAN JOURNAL OF KIDNEY DISEASES Chang, T. I., Li, S., Chen, S., Peralta, C. A., Shlipak, M. G., Fried, L. F., Whaley-Connell, A. T., McCullough, P. A., Tamura, M. K. 2013; 61 (4): S4-S11

  Abstract

  Given the increasing costs and poor outcomes of end-stage renal disease (ESRD), we sought to identify risk factors for ESRD in people with preserved estimated glomerular filtration rate (eGFR), with or without albuminuria, who were at high risk of ESRD.This cohort study included participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP) with eGFR ≥ 60 mL/min/1.73 m(2) at baseline stratified by the presence or absence of albuminuria. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate eGFR. Urine was tested for albuminuria by semiquantitative dipstick. The outcome was the development of treated chronic kidney failure, defined as initiation of maintenance dialysis therapy or kidney transplantation, determined by linkage to the US Renal Data System. We used a Cox model with the Fine-Gray method to assess risk factors for treated chronic kidney failure while accounting for the competing risk of death.During a median follow-up of 4.8 years, 126 of 13,923 participants with albuminuria (16/10,000 patient-years) and 56 of 109,135 participants without albuminuria (1.1/10,000 patient-years) developed treated chronic kidney failure. Diabetes was a strong risk factor for developing treated chronic kidney failure in participants with and without albuminuria (adjusted HRs of 9.3 [95% CI, 5.7-15.3] and 7.8 [95% CI, 4.1-14.8], respectively). Black race, lower eGFR, and higher systolic blood pressure also were associated with higher adjusted risks of developing treated chronic kidney failure.In a diverse high-risk cohort of KEEP participants with preserved eGFR, we showed that diabetes, higher systolic blood pressure, lower eGFR, and black race were risk factors for developing treated chronic kidney failure irrespective of albuminuria status, although the absolute risk of kidney failure in participants without albuminuria was very low. Our findings support testing for kidney disease in high-risk populations, which often have otherwise unrecognized kidney disease.

  View details for DOI 10.1053/j.ajkd.2012.12.016

  View details for PubMedID 23507268

• Advances in CKD Detection and Determination of Prognosis: Executive Summary of the National Kidney Foundation-Kidney Early Evaluation Program (KEEP) 2012 Annual Data Report AMERICAN JOURNAL OF KIDNEY DISEASES Whaley-Connell, A. T., Tamura, M., Jurkovitz, C. T., Kosiborod, M., McCullough, P. A. 2013; 61 (4): S1-S3

  View details for DOI 10.1053/j.ajkd.2013.01.006

  View details for Web of Science ID 000317270600001

  View details for PubMedID 23507265

  View details for PubMedCentralID PMC3608929

• COMPARISON OF MORTALITY PREDICTION MODELS FOR ELDERLY WITH ESRD Cheung, K. L., Montez-Rath, M. E., Tamura, M. W B SAUNDERS CO-ELSEVIER INC. 2013: A32

  View details for Web of Science ID 000317274900070

• Association of Race and Body Mass Index With ESRD and Mortality in CKD Stages 3-4: Results From the Kidney Early Evaluation Program (KEEP) AMERICAN JOURNAL OF KIDNEY DISEASES Babayev, R., Whaley-Connell, A., Kshirsagar, A., Klemmer, P., Navaneethan, S., Chen, S., Li, S., McCullough, P. A., Bakris, G., Bomback, A., KEEP Investigators 2013; 61 (3): 404-412

  Abstract

  A recent cross-sectional analysis of Kidney Early Evaluation Program (KEEP) participants suggested that obesity is a heterogeneous disease state in African Americans and whites with chronic kidney disease (CKD).In longitudinal analyses spanning 8 years of follow-up, we examined whether race and body mass index (BMI) influence end-stage renal disease (ESRD) and mortality rates in participants with CKD stages 3-4.KEEP participants were included in this analysis if they met the following criteria: (1) estimated glomerular filtration rate (eGFR) of 15-59 mL/min/1.73 m(2), (2) white or African American race, and (3) no previous dialysis or transplantation.Survival analyses were performed for the outcomes of ESRD, death, and combined outcome of ESRD or death.Of 14,631 participants with CKD stages 3-4, 28% were African American and 72% were white. African American participants had higher rates of obesity and hypertension, with a higher baseline mean eGFR, higher prevalence of albuminuria, and greater degree of anemia compared with whites. In multivariable models, African American race increased the risk of ESRD (HR, 1.66; 95% CI, 1.26-2.07), but not death (HR, 0.89; 95% CI, 0.76-1.03). In these models, male sex, hypertension, diabetes, lower baseline eGFR, and albuminuria were predictive of higher rates of ESRD; age, male sex, diabetes, lower baseline eGFR, and albuminuria were predictive of overall mortality. There was no significant interaction between race and BMI in the adjusted model for outcomes of ESRD (P = 0.7) or death (P = 0.3).Baseline values used in the analysis are from a cross-sectional data set. Dyslipidemia and secondary hyperparathyroidism were not accounted for in the analysis.African American race was associated with a higher incidence of ESRD, but not mortality. Although obesity may be a heterogeneous disease state in African Americans and whites with CKD, there does not appear to be a significant interaction between race and BMI in progression to ESRD or death.

  View details for DOI 10.1053/j.ajkd.2012.11.038

  View details for Web of Science ID 000314966600010

  View details for PubMedID 23260275

• Effect of More Frequent Hemodialysis on Cognitive Function in the Frequent Hemodialysis Network Trials AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M. K., Unruh, M. L., Nissenson, A. R., Larive, B., Eggers, P. W., Gassman, J., Mehta, R. L., Kliger, A. S., Stokes, J. B. 2013; 61 (2): 228-237

  Abstract

  Cognitive impairment is common in patients with end-stage renal disease receiving hemodialysis 3 times per week.Randomized clinical trial.218 individuals participating in the Frequent Hemodialysis Network (FHN) Daily Trial and 81 participating in the FHN Nocturnal Trial.The Daily Trial tested in-center hemodialysis 6 times per week versus 3 times per week. The Nocturnal Trial tested home nocturnal hemodialysis 6 times per week versus home or in-center hemodialysis 3 times per week.Cognitive function was measured at baseline, month 4, and month 12. The primary outcome was performance on the Trail-Making Test, Form B, a measure of executive function, and a secondary outcome was performance on the Modified Mini-Mental State Examination, a measure of global cognition. The domains of attention, psychomotor speed, memory, and verbal fluency were assessed in 59 participants in the Daily Trial and 19 participants in the Nocturnal Trial.We found no benefit of frequent hemodialysis in either trial for the primary cognitive outcome (Daily Trial: OR for improvement, 0.99; 95% CI, 0.59-1.66; Nocturnal Trial: OR, 1.19; 95% CI, 0.48-2.96). Similarly, there was no benefit of frequent hemodialysis in either trial on global cognition, the secondary cognitive outcome. Exploratory analyses in the Daily Trial suggested possible benefits of frequent hemodialysis for memory and verbal fluency, but not for attention and psychomotor speed. Exploratory analyses in the Nocturnal Trial suggested no benefit of frequent hemodialysis on attention, psychomotor speed, memory, or verbal fluency.Unblinded intervention, small sample.Frequent hemodialysis did not improve executive function or global cognition.

  View details for DOI 10.1053/j.ajkd.2012.09.009

  View details for Web of Science ID 000313591800009

  View details for PubMedCentralID PMC3546160

• The Association between Parathyroid Hormone Levels and Hemoglobin in Diabetic and Nondiabetic Participants in the National Kidney Foundation's Kidney Early Evaluation Program CARDIORENAL MEDICINE Memon, I., Norris, K. C., Bomback, A. S., Peralta, C., Li, S., Chen, S., McCullough, P. A., Whaley-Connell, A., Jurkovitz, C., Tamura, M. K., Saab, G. 2013; 3 (2): 120-127

  Abstract

  Both anemia and secondary hyperparathyroidism are reflections of hormonal failure in chronic kidney disease (CKD). While the association of elevated levels of parathyroid hormone (PTH) and anemia has been studied among those with advanced CKD, less is known about this association in mild-to-moderate CKD.In a cross-sectional analysis, the relationship between PTH and hemoglobin levels was investigated in 10,750 participants in the National Kidney Foundation's Kidney Early Evaluation Program with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2.In the unadjusted analysis, higher PTH levels were associated with lower hemoglobin levels. However, after multivariable adjustment for age, race, gender, smoking status, education, cardiovascular disease, diabetes, hypertension, cancer, albuminuria, BMI, baseline eGFR, calcium, and phosphorus, the direction of association changed. As compared to the first PTH quintile, hemoglobin levels were 0.09 g/dl (95% CI: 0.01-0.18), 0.15 g/dl (95% CI: 0.07-0.24), 0.18 g/dl (95% CI: 0.09-0.26), and 0.13 g/dl (95% CI: 0.07-0.25) higher for the second, third, fourth, and fifth quintiles, respectively. Similarly, each standard deviation increase in natural log transformed PTH was associated with a 0.06 g/dl (95% CI: 0.03-0.09, p = 0.0003) increase in hemoglobin. However, a significant effect modification was seen for diabetes (p = 0.0003). Each standard deviation increase in natural log transformed PTH was associated with a 0.10 g/dl (95% CI: 0.054-0.138, p < 0.0001) increase in hemoglobin, while no association was seen among those without diabetes mellitus.After multivariable adjustment, there was a small positive association between PTH and hemoglobin among diabetics but not among nondiabetics.

  View details for DOI 10.1159/000351229

  View details for Web of Science ID 000321809200005

  View details for PubMedCentralID PMC3721130

• Predialyis Nephrology Care of Older Individuals Approaching End-Stage Renal Disease SEMINARS IN DIALYSIS Winkelmayer, W. C., Tamura, M. K. 2012; 25 (6): 628-632

  Abstract

  Many older patients with advanced CKD approaching ESRD do not receive timely nephrology care, although data suggest that the situation may be improving. In 2005-2008, 43% of older patients who initiated renal replacement therapy had experienced an outpatient nephrologist consultation more than 1 year before starting treatment. Earlier consultation with a nephrologist has been found to provide better access to peritoneal dialysis and kidney transplantation, better preparation for the chosen dialytic modality, and improved survival after start of dialysis or receipt of a kidney transplant. Recent data suggest that older individuals are less likely to receive treatment for ESRD compared with younger individuals in whom almost all receive dialysis treatment or transplantation. Little is known about the role nephrologists play in the decision whether to initiate dialysis or choose a conservative route among older adults with ESRD. Defining the appropriate role and involvement of nephrologists in the decision about initiating renal replacement therapy in older adults seems ripe for further investigation and discussion.

  View details for DOI 10.1111/sdi.12036

  View details for Web of Science ID 000311404400007

  View details for PubMedID 23173891

• A Decade After the KDOQI CKD Guidelines: Impact on the National Kidney Foundation's Kidney Early Evaluation Program (KEEP) AMERICAN JOURNAL OF KIDNEY DISEASES Whaley-Connell, A., Tamura, M., McCullough, P. A. 2012; 60 (5): 692-693

  View details for DOI 10.1053/j.ajkd.2012.08.008

  View details for Web of Science ID 000310508100006

  View details for PubMedID 23067631

• Prevalence and significance of stroke symptoms among patients receiving maintenance dialysis. Neurology Kurella Tamura, M., Meyer, J. B., Saxena, A. B., Huh, J. W., Wadley, V. G., Schiller, B. 2012; 79 (10): 981-987

  Abstract

  The purpose of this cross-sectional study was to determine the prevalence and potential significance of stroke symptoms among end-stage renal disease (ESRD) patients without a prior diagnosis of stroke or TIA.We enrolled 148 participants with ESRD from 5 clinics. Stroke symptoms and functional status, basic and instrumental activities of daily living (ADL, IADL), were ascertained by validated questionnaires. Cognitive function was assessed with a neurocognitive battery. Cognitive impairment was defined as a score 2 SDs below norms for age and education in 2 domains. IADL impairment was defined as needing assistance in at least 1 of 7 IADLs.Among the 126 participants without a prior stroke or TIA, 46 (36.5%) had experienced one or more stroke symptoms. After adjustment for age, sex, race, education, language, diabetes, and cardiovascular disease, participants with stroke symptoms had lower scores on tests of attention, psychomotor speed, and executive function, and more pronounced dependence in IADLs and ADLs (p ≤ 0.01 for all). After adjustment for age, sex, race, education, language, diabetes, and cardiovascular disease, participants with stroke symptoms had a higher likelihood of cognitive impairment (odds ratio [OR] 2.47, 95% confidence interval [CI] 1.03-5.92) and IADL impairment (OR 3.86, 95% CI 1.60-9.28).Stroke symptoms are common among patients with ESRD and strongly associated with impairments in cognition and functional status. These findings suggest that clinically significant stroke events may go undiagnosed in this high-risk population.

  View details for DOI 10.1212/WNL.0b013e31826845e9

  View details for PubMedID 22875090

• The IDEAL Trial: A Closer Look SEMINARS IN DIALYSIS Tamura, M. K. 2012; 25 (5): 523-525

  View details for DOI 10.1111/j.1525-139X.2012.01118.x

  View details for Web of Science ID 000308966800008

  View details for PubMedID 22823252

• Prevalence and significance of stroke symptoms among patients receiving maintenance dialysis NEUROLOGY Tamura, M. K., Meyer, J. B., Saxena, A. B., Huh, J. W., Wadley, V. G., Schiller, B. 2012; 79 (10): 981-987

  Abstract

  The purpose of this cross-sectional study was to determine the prevalence and potential significance of stroke symptoms among end-stage renal disease (ESRD) patients without a prior diagnosis of stroke or TIA.We enrolled 148 participants with ESRD from 5 clinics. Stroke symptoms and functional status, basic and instrumental activities of daily living (ADL, IADL), were ascertained by validated questionnaires. Cognitive function was assessed with a neurocognitive battery. Cognitive impairment was defined as a score 2 SDs below norms for age and education in 2 domains. IADL impairment was defined as needing assistance in at least 1 of 7 IADLs.Among the 126 participants without a prior stroke or TIA, 46 (36.5%) had experienced one or more stroke symptoms. After adjustment for age, sex, race, education, language, diabetes, and cardiovascular disease, participants with stroke symptoms had lower scores on tests of attention, psychomotor speed, and executive function, and more pronounced dependence in IADLs and ADLs (p ≤ 0.01 for all). After adjustment for age, sex, race, education, language, diabetes, and cardiovascular disease, participants with stroke symptoms had a higher likelihood of cognitive impairment (odds ratio [OR] 2.47, 95% confidence interval [CI] 1.03-5.92) and IADL impairment (OR 3.86, 95% CI 1.60-9.28).Stroke symptoms are common among patients with ESRD and strongly associated with impairments in cognition and functional status. These findings suggest that clinically significant stroke events may go undiagnosed in this high-risk population.

  View details for DOI 10.1212/WNL.0b013e31826845e9

  View details for Web of Science ID 000308674000012

  View details for PubMedCentralID PMC3430712

• Awareness of Kidney Disease and Relationship to End-stage Renal Disease and Mortality AMERICAN JOURNAL OF MEDICINE Whaley-Connell, A., Shlipak, M. G., Inker, L. A., Tamura, M. K., Bomback, A. S., Saab, G., Szpunar, S. M., McFarlane, S. I., Li, S., Chen, S., Norris, K., Bakris, G. L., McCullough, P. A. 2012; 125 (7): 661-669

  Abstract

  Often, patients with chronic kidney disease are reported to be unaware of it. We prospectively evaluated the association between awareness of kidney disease to end-stage renal disease and mortality.We utilized 2000-2009 data from the National Kidney Foundation's Kidney Early Evaluation Program. Mortality was determined by cross reference to the Social Security Administration Death Master File and development of end stage by cross reference with the United States Renal Data System.Of 109,285 participants, 28,244 (26%) had chronic kidney disease defined by albuminuria or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2). Only 9% (n=2660) reported being aware of kidney disease. Compared with those who were not aware, participants aware of chronic kidney disease had lower eGFR (49 vs 62 mL/min/1.73 m(2)) and a higher prevalence of albuminuria (52% vs. 46%), diabetes (47% vs 42%), cardiovascular disease (43% vs 28%), and cancer (23% vs 14%). Over 8.5 years of follow-up, aware participants compared with those unaware had a lower rate of survival for end stage (83% and 96%) and mortality (78% vs 81%), P <.001. After adjustment for demographics, socioeconomic factors, comorbidity, and severity of kidney disease, aware participants continued to demonstrate an increased risk for end-stage renal disease (hazard ratio 1.37; 95% confidence interval, 1.07-1.75; P <.0123) and mortality (hazard ratio 1.27; 95% confidence interval, 1.07-1.52; P <.0077) relative to unaware participants with chronic kidney disease.Among patients identified as having chronic kidney disease at a health screening, only a small proportion had been made aware of their diagnosis previously by clinicians. This subgroup was at a disproportionately high risk for mortality and end-stage renal disease.

  View details for DOI 10.1016/j.amjmed.2011.11.026

  View details for Web of Science ID 000305752700019

  View details for PubMedID 22626510

  View details for PubMedCentralID PMC3383388

• Factors Associated With Depressive Symptoms and Use of Antidepressant Medications Among Participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies AMERICAN JOURNAL OF KIDNEY DISEASES Fischer, M. J., Xie, D., Jordan, N., Kop, W. J., Krousel-Wood, M., Tamura, M. K., Kusek, J. W., Ford, V., Rosen, L. K., Strauss, L., Teal, V. L., Yaffe, K., Powe, N. R., Lash, J. P. 2012; 60 (1): 27-38

  Abstract

  Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied.Cross-sectional analysis.Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at 7 centers in 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois in 2005-2008.Depressive symptoms measured by Beck Depression Inventory (BDI).Demographic and clinical factors.Elevated depressive symptoms (BDI score ≥11) and antidepressant medication use.Of 3,853 participants, 27.4% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 31.0% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 23.6% for participants with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and 33.8% of those with eGFR <30 mL/min/1.73 m(2). Lower eGFR (OR per 10-mL/min/1.73 m(2) decrease, 1.10; 95% CI, 1.04-1.17), and non-Hispanic black race (OR, 1.42; 95% CI, 1.16-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, whereas female sex was associated with greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher urine albumin levels were associated with decreased odds of antidepressant use (P < 0.05 for each).Absence of clinical diagnosis of depression and use of nonpharmacologic treatments.Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. Individuals of racial and ethnic minority background and with more advanced CKD had a greater burden of elevated depressive symptoms and lower use of antidepressant medications.

  View details for DOI 10.1053/j.ajkd.2011.12.033

  View details for Web of Science ID 000305406200007

  View details for PubMedID 22497791

• Treated and Untreated Kidney Failure in Older Adults What's the Right Balance? JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Tamura, M. K., Winkelmayer, W. C. 2012; 307 (23): 2545-2546

  View details for Web of Science ID 000305391400033

  View details for PubMedID 22797456

• Timing of initiation of dialysis: time for a new direction? CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Abra, G., Tamura, M. K. 2012; 21 (3): 329-333

  Abstract

  The past 15 years have seen tremendous growth in the initiation of dialysis at higher levels of kidney function in the setting of mixed evidence and at great societal economic cost. We review recent data on the early dialysis initiation trend, the clinical and economic impact of early dialysis initiation and the future implications for the management of advanced chronic kidney disease (CKD).The percentage of patients who initiate dialysis with an estimated glomerular filtration rate (eGFR) above 10  ml/min/1.73m(2) is now greater than 50%, including 20% who initiate with an eGFR above 15 ml/min/1.73m(2). The drivers behind these findings are probably diverse but recent literature does not seem to support a higher symptom burden among the ageing CKD population as the major cause. The Initiating Dialysis Early And Late (IDEAL) trial provides guidance on the safety of waiting for symptoms or lower levels of estimated glomerular filtration rate prior to beginning dialysis. In addition, economic analyses based on the IDEAL and US Renal Data System findings suggest that significant cost savings could be achieved by reversing the early initiation trend.These findings should help clinicians and policy makers looking to rein in costs while maintaining the quality of CKD care.

  View details for DOI 10.1097/MNH.0b013e328351c244

  View details for Web of Science ID 000302769500014

  View details for PubMedID 22388556

  View details for PubMedCentralID PMC3458516

• Validation of the NINDS-CSN 5-Minute Battery for Vascular Cognitive Impairment 64th Annual Meeting of the American-Academy-of-Neurology (AAN) Kennedy, R., Wadley, V., McClure, L., Unverzagt, F., Crowe, M., Kelley, B., Nyenhuis, D., Kana, B., Marceaux, J., Tamura, M., Howard, V., Howard, G. LIPPINCOTT WILLIAMS & WILKINS. 2012

  View details for Web of Science ID 000303204802125

• Blood Pressure Components and End-stage Renal Disease in Persons With Chronic Kidney Disease The Kidney Early Evaluation Program (KEEP) ARCHIVES OF INTERNAL MEDICINE Peralta, C. A., Norris, K. C., Li, S., Chang, T. I., Tamura, M. K., Jolly, S. E., Bakris, G., McCullough, P. A., Shlipak, M. 2012; 172 (1): 41-47

  Abstract

  Treatment of hypertension is difficult in chronic kidney disease (CKD), and blood pressure goals remain controversial. The association between each blood pressure component and end-stage renal disease (ESRD) risk is less well known.We studied associations of systolic and diastolic blood pressure (SBP and DBP, respectively) and pulse pressure (PP) with ESRD risk among 16,129 Kidney Early Evaluation Program (KEEP) participants with an estimated glomerular filtration rate of 60 mL/min/1.73 m(2) using Cox proportional hazards. We estimated the prevalence and characteristics associated with uncontrolled hypertension (SBP ≥ 150 or DBP ≥ 90 mm Hg).The mean (SD) age of participants was 69 (12) years; 25% were black, 6% were Hispanic, and 43% had diabetes mellitus. Over 2.87 years, there were 320 ESRD events. Higher SBP was associated with higher ESRD risk, starting at SBP of 140 mm Hg or higher. After sex and age adjustment, compared with SBP lower than 130 mm Hg, hazard ratios (HRs) were 1.08 (95% CI, 0.74-1.59) for SBP of 130 to 139 mm Hg, 1.72 (95% CI, 1.21-2.45) for SBP of 140 to 149 mm Hg, and 3.36 (95% CI, 2.51-4.49) for SBP of 150 mm Hg or greater. After full adjustment, HRs for ESRD were 1.27 (95% CI, 0.88-1.83) for SBP of 140 to 149 mm Hg and 1.36 (95% CI, 1.02-1.85) for SBP of 150 mm Hg or higher. Persons with DBP of 90 mm Hg or higher were at higher risk for ESRD compared with persons with DBP of 60 to 74 mm Hg (HR, 1.81; 95% CI, 1.33-2.45). Higher PP was also associated with higher ESRD risk (HR, 1.44 [95% CI, 1.00-2.07] for PP ≥ 80 mm Hg compared with PP < 50 mm Hg). Adjustment for SBP attenuated this association. More than 33% of participants had uncontrolled hypertension (SBP ≥ 150 mm Hg or DBP ≥ 90 mm Hg), mostly due to isolated systolic hypertension (54%).In this large, diverse, community-based sample, we found that high SBP seemed to account for most of the risk of progression to ESRD. This risk started at SBP of 140 mm Hg rather than the currently recommended goal of less than 130 mm Hg, and it was highest among those with SBP of at least 150 mm Hg. Treatment strategies that preferentially lower SBP may be required to improve BP control in CKD.

  View details for Web of Science ID 000298958900008

  View details for PubMedID 22232147

  View details for PubMedCentralID PMC3417125

• Combining Angiotensin Receptor Blockers With ACE Inhibitors in Elderly Patients AMERICAN JOURNAL OF KIDNEY DISEASES Anand, S., Tamura, M. K. 2012; 59 (1): 11-14

  View details for DOI 10.1053/j.ajkd.2011.09.002

  View details for Web of Science ID 000298153600006

  View details for PubMedID 21995968

• Association of Self-reported Physical Activity With Laboratory Markers of Nutrition and Inflammation: The Comprehensive Dialysis Study JOURNAL OF RENAL NUTRITION Anand, S., Chertow, G. M., Johansen, K. L., Grimes, B., Tamura, M. K., Dalrymple, L. S., Kaysen, G. A. 2011; 21 (6): 429-437

  Abstract

  Patients on dialysis maintain extremely low levels of physical activity. Prior studies have demonstrated a direct correlation between nutrition and physical activity but provide conflicting data on the link between inflammation and physical activity. Using a cohort of patients new to dialysis from the Comprehensive Dialysis Study (CDS), we examined associations of self-reported physical activity with laboratory markers of nutrition and inflammation.Between June 2005 and June 2007, CDS collected data on self-reported physical activity, nutrition, and health-related quality of life from patients starting dialysis in 296 facilities located throughout the United States. Baseline serum samples were collected from participants in a nutrition sub-study of CDS.Serum albumin and prealbumin were measured as markers of nutrition, and C-reactive protein (CRP) and α-1-acid glycoprotein as markers of inflammation. Self-reported physical activity was characterized by the maximum activity score (MAS) and adjusted activity score (AAS) of the Human Activity Profile.The mean age of participants in the analytic cohort (n = 201) was 61 years. The MAS and AAS were below the 10th and first percentile, respectively, in comparison with healthy 60 year-old norms. Both activity scores were directly correlated with albumin (r(2) = 0.3, P < .0001) and prealbumin (r(2) = 0.3, P < .0001), and inversely correlated with CRP (AAS: r(2) = -0.2, P = .01; MAS: r(2) = -0.1, P = .08). In multivariate analyses adjusting for age, gender, race/ethnicity, diabetes status, and center, both activity scores were directly correlated with prealbumin and inversely correlated with CRP.Patients new to dialysis with laboratory-based evidence of malnutrition and/or inflammation are likely to report lower levels of physical activity.

  View details for DOI 10.1053/j.jrn.2010.09.007

  View details for PubMedID 21239185

• Vitamin D deficiency, self-reported physical activity and health-related quality of life: the Comprehensive Dialysis Study NEPHROLOGY DIALYSIS TRANSPLANTATION Anand, S., Kaysen, G. A., Chertow, G. M., Johansen, K. L., Grimes, B., Dalrymple, L. S., Tamura, M. K. 2011; 26 (11): 3683-3688

  Abstract

  As research has identified a wide array of biological functions of vitamin D, the consequences of vitamin D deficiency in persons with chronic kidney disease has attracted increased attention. The objective of this study was to determine the extent of 25-hydroxyvitamin D (25-OH vitamin D) deficiency and its associations with self-reported physical activity and health-related quality of life (HRQoL) among participants of the Comprehensive Dialysis Study (CDS).The nutrition substudy of the CDS enrolled patients new to dialysis from 68 dialysis units throughout the USA. Baseline 25-OH vitamin D concentration was measured using the Direct Enzyme Immunoassay (Immunodiagnostic Systems Inc.). Physical activity was measured with the Human Activity Profile (HAP); the Medical Outcomes Study Short Form-12 (SF-12) was employed to measure HRQoL.Mean age of the participants (n = 192) was 62 years. There were 124 participants (65%) with 25-OH vitamin D concentrations < 15 ng/mL, indicating deficiency, and 64 (33%) with 25-OH vitamin D ≥ 15 to <30 ng/mL, indicating insufficiency. After adjusting for age, sex, race/ethnicity, diabetes, season and center, lower 25-OH vitamin D concentrations were independently associated with lower scores on the HAP and on the Mental Component Summary of the SF-12 (P < 0.05 for both), but not with the Physical Component Summary of the SF-12.In a well-characterized cohort of incident dialysis patients, lower 25-OH vitamin D concentrations were associated with lower self-reported physical activity and poorer self-reported mental health.

  View details for DOI 10.1093/ndt/gfr098

  View details for PubMedID 21430182

• Albuminuria, kidney function, and the incidence of cognitive impairment among adults in the United States. American journal of kidney diseases Kurella Tamura, M., Muntner, P., Wadley, V., Cushman, M., Zakai, N. A., Bradbury, B. D., Kissela, B., Unverzagt, F., Howard, G., Warnock, D., McClellan, W. 2011; 58 (5): 756-763

  Abstract

  Albuminuria and estimated glomerular filtration rate (eGFR) are each associated with increased risk of cognitive impairment, but their joint association is unknown.Prospective cohort study.A US national sample of 19,399 adults without cognitive impairment at baseline participating in the REGARDS (Reasons for Geographic and Racial Disparities in Stroke) Study.Albuminuria was assessed using urine albumin-creatinine ratio (UACR) and GFR was estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation.Incident cognitive impairment was defined as score ≤4 on the 6-Item Screener at the last follow-up visit.During a mean follow-up of 3.8 ± 1.5 years, UACRs of 30-299 and ≥300 mg/g were associated independently with 31% and 57% higher risk of cognitive impairment, respectively, relative to individuals with UACR <10 mg/g. This finding was strongest for those with high eGFRs and attenuated at lower levels (P = 0.04 for trend). Relative to eGFR ≥60 mL/min/1.73 m(2), eGFR <60 mL/min/1.73 m(2) was not associated independently with cognitive impairment. However, after stratifying by UACR, eGFR <60 mL/min/1.73 m(2) was associated with a 30% higher risk of cognitive impairment in participants with UACR <10 mg/g, but not higher UACRs (P = 0.04 for trend).Single measures of albuminuria and eGFR, screening test of cognition.When eGFR was preserved, albuminuria was associated independently with incident cognitive impairment. When albuminuria was <10 mg/g, low eGFR was associated independently with cognitive impairment. Albuminuria and low eGFR are complementary, but not additive, risk factors for incident cognitive impairment.

  View details for DOI 10.1053/j.ajkd.2011.05.027

  View details for PubMedID 21816528

• Albuminuria, Kidney Function, and the Incidence of Cognitive Impairment Among Adults in the United States AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M. K., Muntner, P., Wadley, V., Cushman, M., Zakai, N. A., Bradbury, B. D., Kissela, B., Unverzagt, F., Howard, G., Warnock, D., McClellan, W. 2011; 58 (5): 756-763

  Abstract

  Albuminuria and estimated glomerular filtration rate (eGFR) are each associated with increased risk of cognitive impairment, but their joint association is unknown.Prospective cohort study.A US national sample of 19,399 adults without cognitive impairment at baseline participating in the REGARDS (Reasons for Geographic and Racial Disparities in Stroke) Study.Albuminuria was assessed using urine albumin-creatinine ratio (UACR) and GFR was estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation.Incident cognitive impairment was defined as score ≤4 on the 6-Item Screener at the last follow-up visit.During a mean follow-up of 3.8 ± 1.5 years, UACRs of 30-299 and ≥300 mg/g were associated independently with 31% and 57% higher risk of cognitive impairment, respectively, relative to individuals with UACR <10 mg/g. This finding was strongest for those with high eGFRs and attenuated at lower levels (P = 0.04 for trend). Relative to eGFR ≥60 mL/min/1.73 m(2), eGFR <60 mL/min/1.73 m(2) was not associated independently with cognitive impairment. However, after stratifying by UACR, eGFR <60 mL/min/1.73 m(2) was associated with a 30% higher risk of cognitive impairment in participants with UACR <10 mg/g, but not higher UACRs (P = 0.04 for trend).Single measures of albuminuria and eGFR, screening test of cognition.When eGFR was preserved, albuminuria was associated independently with incident cognitive impairment. When albuminuria was <10 mg/g, low eGFR was associated independently with cognitive impairment. Albuminuria and low eGFR are complementary, but not additive, risk factors for incident cognitive impairment.

  View details for DOI 10.1053/j.ajkd.2011.05.027

  View details for Web of Science ID 000296385700013

  View details for PubMedCentralID PMC3199339

• LESS IS MORE Trends in Timing of Initiation of Chronic Dialysis in the United States ARCHIVES OF INTERNAL MEDICINE O'Hare, A. M., Choi, A. I., Boscardin, W. J., Clinton, W. L., Zawadzki, I., Hebert, P. L., Tamura, M. K., Taylor, L., Larson, E. B. 2011; 171 (18): 1663-1669

  Abstract

  During the past decade, a trend has been observed in the United States toward initiation of chronic dialysis at higher levels of estimated glomerular filtration rate. This likely reflects secular trends in the composition of the dialysis population and a tendency toward initiation of dialysis earlier in the course of kidney disease.The goal of this study was to generate model-based estimates of the magnitude of changes in the timing of dialysis initiation between 1997 and 2007. We used information from a national registry for end-stage renal disease on estimated glomerular filtration rate at initiation among patients who received their first chronic dialysis treatment in 1997 or 2007. We used information regarding predialysis estimated glomerular filtration rate slope from an integrated health care system.After accounting for changes in the characteristics of new US dialysis patients from 1997 to 2007, we estimate that chronic dialysis was initiated a mean of 147 days earlier (95% confidence interval, 134-160) in the later compared with the earlier year. Differences in timing were consistent across a range of patient subgroups but were most pronounced for those aged 75 years or older; the mean difference in timing in that subgroup was 233 days (95% confidence interval, 206-267).Chronic dialysis appears to have been initiated substantially earlier in the course of kidney disease in 2007 compared with 1997. In the absence of strong evidence to suggest that earlier initiation of chronic dialysis is beneficial, these findings call for careful evaluation of contemporary dialysis initiation practices in the United States.

  View details for Web of Science ID 000295695600012

• Correlates of insulin resistance in older individuals with and without kidney disease NEPHROLOGY DIALYSIS TRANSPLANTATION Landau, M., Kurella-Tamura, M., Shlipak, M. G., Kanaya, A., Strotmeyer, E., Koster, A., Satterfield, S., Simsonick, E. M., Goodpaster, B., Newman, A. B., Fried, L. F. 2011; 26 (9): 2814-2819

  Abstract

  Chronic kidney disease (CKD) is associated with insulin resistance (IR). Prior studies have found that in individuals with CKD, leptin is associated with fat mass but resistin is not and the associations with adiponectin are conflicting. This suggests that the mechanism and factors associated with IR in CKD may differ.Of the 2418 individuals without reported diabetes at baseline, participating in the Health, Aging and Body Composition study, a study in older individuals aged 70-79 years, 15.6% had CKD defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) based on cystatin C. IR was defined as the upper quartile of the homeostasis model assessment. The association of visceral and subcutaneous abdominal fat, percent body fat, muscle fat, lipids, inflammatory markers and adiponectin were tested with logistic regression. Interactions were checked to assess whether the factors associated with IR were different in those with and without CKD.Individuals with IR had a lower eGFR (80.7 ± 20.9 versus 75.6 ± 19.6, P < 0.001). After multivariable adjustment, eGFR (odds ratio per 10 mL/min/1.73 m(2) 0.92, 95% confidence interval 0.87-0.98) and CKD (1.41, 1.04-1.92) remained independently associated with IR. In individuals with and without CKD, the significant predictors of IR were male sex, black race, higher visceral fat, abdominal subcutaneous fat and triglycerides. In individuals without CKD, IR was associated with lower high-density lipoprotein and current nonsmoking status in multivariate analysis. In contrast, among individuals with CKD, interleukin-6 (IL-6) was independently associated with IR. There was a significant interaction of eGFR with race and IL-6 with a trend for adionectin but no significant interactions with CKD (P > 0.1). In the fully adjusted model, there was a trend for an interaction with adiponectin for eGFR (P = 0.08) and significant for CKD (P = 0.04 ), where adiponectin was associated with IR in those without CKD but not in those with CKD.In mainly Stage 3 CKD, kidney function is associated with IR; except for adiponectin, the correlates of IR are similar in those with and without CKD.

  View details for DOI 10.1093/ndt/gfq817

  View details for Web of Science ID 000295231600016

  View details for PubMedID 21248294

  View details for PubMedCentralID PMC3203409

• Predialysis Nephrology Care of Older Patients Approaching End-stage Renal Disease ARCHIVES OF INTERNAL MEDICINE Winkelmayer, W. C., Liu, J., Chertow, G. M., Tamura, M. K. 2011; 171 (15): 1371-1378

  Abstract

  Little is known about trends in the timing of first nephrology consultation and associated outcomes among older patients initiating dialysis.Data from patients aged 67 years or older who initiated dialysis in the United States between January 1, 1996, and December 31, 2006, were stratified by timing of the earliest identifiable nephrology visit. Trends of earlier nephrology consultation were formally examined in light of concurrently changing case mix and juxtaposed with trends in 1-year mortality rates after initiation of dialysis.Among 323,977 older patients initiating dialysis, the proportion of patients receiving nephrology care less than 3 months before initiation of dialysis decreased from 49.6% (in 1996) to 34.7% (in 2006). Patients initiated dialysis with increasingly preserved kidney function, from a mean estimated glomerular filtration rate of 8 mL/min/1.73 m(2) in 1996 to 12 mL/min/1.73 m(2) in 2006. Patients were less anemic in later years, which was partly attributable to increased use of erythropoiesis-stimulating agents, and fewer used peritoneal dialysis as the initial modality. During the same period, crude 1-year mortality rates remained unchanged (annual change in mortality rate, +0.2%; 95% confidence interval, 0% to +0.4%). Adjustment for changes in demographic and comorbidity patterns yielded estimated annual reductions in 1-year mortality rates of 0.9% (95% confidence interval, 0.7% to 1.1%), which were explained only partly by concurrent trends toward earlier nephrology consultation (annual mortality reduction after accounting for timing of nephrology care was attenuated to 0.4% [0.2% to 0.6%]).Despite significant trends toward earlier use of nephrology consultation among older patients approaching maintenance dialysis, we observed no material improvement in 1-year survival rates after dialysis initiation during the same time period.

  View details for Web of Science ID 000293642800013

  View details for PubMedID 21824952

  View details for PubMedCentralID PMC4123329

• Association of Educational Attainment With Chronic Disease and Mortality: The Kidney Early Evaluation Program (KEEP) AMERICAN JOURNAL OF KIDNEY DISEASES Choi, A. I., Weekley, C. C., Chen, S., Li, S., Tamura, M. K., Norris, K. C., Shlipak, M. G. 2011; 58 (2): 228-234

  Abstract

  Recent reports have suggested a close relationship between education and health, including mortality, in the United States.Observational cohort.We studied 61,457 participants enrolled in a national health screening initiative, the National Kidney Foundation's Kidney Early Evaluation Program (KEEP).Self-reported educational attainment.Chronic diseases (hypertension, diabetes, cardiovascular disease, reduced kidney function, and albuminuria) and mortality.We evaluated cross-sectional associations between self-reported educational attainment with the chronic diseases listed using logistic regression models adjusted for demographics, access to care, behaviors, and comorbid conditions. The association of educational attainment with survival was determined using multivariable Cox proportional hazards regression.Higher educational attainment was associated with a lower prevalence of each of the chronic conditions listed. In multivariable models, compared with persons not completing high school, college graduates had a lower risk of each chronic condition, ranging from 11% lower odds of decreased kidney function to 37% lower odds of cardiovascular disease. During a mean follow-up of 3.9 (median, 3.7) years, 2,384 (4%) deaths occurred. In the fully adjusted Cox model, those who had completed college had 24% lower mortality compared with participants who had completed at least some high school.Lack of income data does not allow us to disentangle the independent effects of education from income.In this diverse contemporary cohort, higher educational attainment was associated independently with a lower prevalence of chronic diseases and short-term mortality in all age and race/ethnicity groups.

  View details for DOI 10.1053/j.ajkd.2011.02.388

  View details for Web of Science ID 000293010000012

  View details for PubMedID 21601328

  View details for PubMedCentralID PMC3144262

• To Predict Dementia, Should We Be Mindful of the Kidneys? CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K. 2011; 6 (6): 1232-1234

  View details for DOI 10.2215/CJN.03390411

  View details for Web of Science ID 000291500900002

  View details for PubMedID 21566105

• Special considerations in the management of chronic kidney disease in the elderly. Dialysis & transplantation Cheung, K. L., Soman, S., Tamura, M. K. 2011; 40 (6): 241-243

  View details for DOI 10.1002/dat.20571

  View details for PubMedID 21799548

  View details for PubMedCentralID PMC3142958

• Special Considerations in the Management of Chronic Kidney Disease in the Elderly DIALYSIS & TRANSPLANTATION Cheung, K. L., Soman, S., Tamura, M. K. 2011; 40 (6): 241-243

  View details for DOI 10.1002/dat.20571

  View details for Web of Science ID 000291561300004

  View details for PubMedCentralID PMC3142958

• DISEASE STATE AWARENESS, KIDNEY DISEASE, AND RELATIONSHIP TO ESRD AND DEATH Whaley-Connell, A., Saab, G., Sowers, J., Szpunar, S., Stevens, L., Shlipak, M., Bomback, A., Tamura, M., McFarlane, S., Li, S., Chen, S., Collins, A., Norris, K., Bakris, G., McCullough, P. W B SAUNDERS CO-ELSEVIER INC. 2011: A105

  View details for Web of Science ID 000288657100355

• MORTALITY RISK ASSESSMENT IN THE ELDERLY WITH ESRD Cheung, K., Tamura, M. W B SAUNDERS CO-ELSEVIER INC. 2011: A32

  View details for Web of Science ID 000288657100064

• Comparison of the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study Equations: Risk Factors for and Complications of CKD and Mortality in the Kidney Early Evaluation Program (KEEP) AMERICAN JOURNAL OF KIDNEY DISEASES Stevens, L. A., Li, S., Tamura, M. K., Chen, S., Vassalotti, J. A., Norris, K. C., Whaley-Connell, A. T., Bakris, G. L., McCullough, P. A. 2011; 57 (3): S9-S16

  Abstract

  The National Kidney Foundation has recommended that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation replace the Modification of Diet in Renal Disease (MDRD) Study equation. Before implementing this change in the Kidney Early Evaluation Program (KEEP), we compared characteristics of reclassified individuals and mortality risk predictions using the new equation.Of 123,704 eligible KEEP participants, 116,321 with data available for this analysis were included. Glomerular filtration rate (GFR) was estimated using the MDRD Study (eGFR(MDRD)) and CKD-EPI (eGFR(CKD-EPI)) equations with creatinine level calibrated to standardized methods. Participants were characterized by eGFR category: >120, 90-119, 60-89, 45-59, 30-44, and <30 mL/min/1.73 m(2). Clinical characteristics ascertained included age, race, sex, diabetes, hypertension, coronary artery disease, congestive heart failure, cerebrovascular disease, peripheral vascular disease, and anemia. Mortality was determined over a median of 3.7 years of follow-up.The prevalence of eGFR(CKD-EPI) <60 mL/min/1.73 m(2) was 14.3% compared with 16.8% using eGFR(MDRD). Using eGFR(CKD-EPI), 20,355 participants (17.5%) were reclassified to higher eGFR categories, and 3,107 (2.7%), to lower categories. Participants reclassified upward were younger and less likely to have chronic conditions, with a lower risk of mortality. A total of 3,601 deaths (3.1%) were reported. Compared with participants classified to eGFR of 45-59 mL/min/1.73 m(2) using both equations, those with eGFR(CKD-EPI) of 60-89 mL/min/1.73 m(2) had a lower mortality incidence rate (6.4 [95% CI, 5.1-7.7] vs 18.5 [95% CI, 17.1-19.9]). Results were similar for all eGFR categories. Net reclassification improvement was 0.159 (P < 0.001).The CKD-EPI equation reclassifies people at lower risk of CKD and death into higher eGFR categories, suggesting more accurate categorization. The CKD-EPI equation will be used to report eGFR in KEEP.

  View details for DOI 10.1053/j.ajkd.2010.11.007

  View details for Web of Science ID 000287472800003

  View details for PubMedID 21338849

  View details for PubMedCentralID PMC3298760

• Palliative Care in CKD: The Earlier the Better AMERICAN JOURNAL OF KIDNEY DISEASES Germain, M. J., Tamura, M., Davison, S. N. 2011; 57 (3): 378-380

  View details for DOI 10.1053/j.ajkd.2010.12.001

  View details for Web of Science ID 000287439500005

  View details for PubMedID 21168946

• Comparison of CKD Awareness in a Screening Population Using the Modification of Diet in Renal Disease (MDRD) Study and CKD Epidemiology Collaboration (CKD-EPI) Equations AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M. K., Anand, S., Li, S., Chen, S., Whaley-Connell, A. T., Stevens, L. A., Norris, K. C. 2011; 57 (3): S17-S23

  View details for DOI 10.1053/j.ajkd.2010.11.008

  View details for Web of Science ID 000287472800004

• Comparison of CKD awareness in a screening population using the Modification of Diet in Renal Disease (MDRD) study and CKD Epidemiology Collaboration (CKD-EPI) equations. American journal of kidney diseases Kurella Tamura, M., Anand, S., Li, S., Chen, S., Whaley-Connell, A. T., Stevens, L. A., Norris, K. C. 2011; 57 (3): S17-23

  Abstract

  Low awareness of chronic kidney disease (CKD) may reflect uncertainty about the accuracy or significance of a CKD diagnosis in individuals otherwise perceived to be low risk. Whether reclassification of CKD severity using the CKD Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) modifies estimates of CKD awareness is unknown.In this cross-sectional study, we used data collected from 2000-2009 for 26,213 participants in the Kidney Early Evaluation Program (KEEP), a community-based screening program, with CKD based on GFR estimated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation and measurement of albuminuria. We assessed CKD awareness after CKD stage was reclassified using the CKD-EPI equation.Of 26,213 participants with CKD based on GFR estimated using the MRDR equation (eGFR(MDRD)), 23,572 (90%) also were classified with CKD based on eGFR(CKD-EPI). Based on eGFR(MDRD), 9.5% of participants overall were aware of CKD, as were 4.9%, 6.3%, 9.2%, 41.9%, and 59.2% with stages 1-5, respectively. Based on eGFR(CKD-EPI), 10.0% of participants overall were aware of CKD, as were 5.1%, 6.6%, 10.0%, 39.3%, and 59.4% with stages 1-5, respectively. Reclassification to a less advanced CKD stage using eGFR(CKD-EPI) was associated with lower odds for awareness (OR, 0.58; 95% CI, 0.50-0.67); reclassification to a more advanced stage was associated with higher odds for awareness (OR, 1.50; 95% CI, 1.05-2.13) after adjustment for confounding factors. Of participants unaware of CKD, 10.6% were reclassified as not having CKD using eGFR(CKD-EPI).Using eGFR(CKD-EPI) led to a modest increase in overall awareness rates, primarily due to reclassification of low-risk unaware participants.

  View details for DOI 10.1053/j.ajkd.2010.11.008

  View details for PubMedID 21338846

• Comparison of the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study Equations: Prevalence of and Risk Factors for Diabetes Mellitus in CKD in the Kidney Early Evaluation Program (KEEP) AMERICAN JOURNAL OF KIDNEY DISEASES McFarlane, S. I., McCullough, P. A., Sowers, J. R., Soe, K., Chen, S., Li, S., Vassalotti, J. A., Stevens, L. A., Salifu, M. O., Tamura, M. K., Bomback, A. S., Norris, K. C., Collins, A. J., Bakris, G. L., Whaley-Connell, A. T. 2011; 57 (3): S24-S31

  Abstract

  Diabetes is a leading cause of chronic kidney disease (CKD). Whether reclassification of CKD stages based on glomerular filtration rate estimated using the CKD Epidemiology Collaboration (CKD-EPI) equation versus the Modification of Diet in Renal Disease (MDRD) Study equation modifies estimates of prevalent risk factors across stages is unknown.This is a cross-sectional analysis of data from the Kidney Early Evaluation Program (KEEP), a community-based health screening program targeting individuals 18 years and older with diabetes, hypertension, or a family history of diabetes, hypertension, or kidney disease. Of 109,055 participants, 68.2% were women and 31.8% were African American. Mean age was 55.3 ± 0.05 years. Clinical, demographic, and laboratory data were collected from August 2000 through December 2009. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations.CKD was present in 25.6% and 23.5% of the study population using the MDRD Study and CKD-EPI equations, respectively. Diabetes was present in 42.4% and 43.8% of participants with CKD, respectively. Prevalent risk factors for diabetes included obesity (body mass index >30 kg/m(2)), 44.0%; hypertension, 80.5%; cardiovascular disease, 23.2%; family history of diabetes, 55.9%; and dyslipidemia, 43.0%. In a logistic regression model after adjusting for age and other risk factors, odds for diabetes increased significantly compared with no CKD with each CKD stage based on the CKD-EPI equation and similarly with stages based on the MDRD Study equation. Using a CKD-EPI-adjusted model, ORs were: stage 1, 2.08 (95% CI, 1.90-2.27); stage 2, 1.86 (95% CI, 1.72-2.02); stage 3, 1.23 (95% CI, 1.17-1.30); stage 4, 1.69 (95% CI, 1.42-2.03); and stage 5, 2.46 (95% CI, 1.46-4.14).Using the CKD-EPI equation led to a lower prevalence of CKD but to similar diabetes prevalence rates associated with CKD across all stages compared with the MDRD Study equation. Diabetes and other CKD risk factor prevalence was increased compared with the non-CKD population.

  View details for DOI 10.1053/j.ajkd.2010.11.009

  View details for Web of Science ID 000287472800005

  View details for PubMedID 21338847

  View details for PubMedCentralID PMC3237700

• Vascular Risk Factors and Cognitive Impairment in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Xie, D., Yaffe, K., Cohen, D. L., Teal, V., Kasner, S. E., Messe, S. R., Sehgal, A. R., Kusek, J., DeSalvo, K. B., Cornish-Zirker, D., Cohan, J., Seliger, S. L., Chertow, G. M., Go, A. S. 2011; 6 (2): 248-256

  Abstract

  Cognitive impairment is common among persons with chronic kidney disease, but the extent to which nontraditional vascular risk factors mediate this association is unclear.We conducted cross-sectional analyses of baseline data collected from adults with chronic kidney disease participating in the Chronic Renal Insufficiency Cohort study. Cognitive impairment was defined as a Modified Mini-Mental State Exam score>1 SD below the mean score.Among 3591 participants, the mean age was 58.2±11.0 years, and the mean estimated GFR (eGFR) was 43.4±13.5 ml/min per 1.73 m2. Cognitive impairment was present in 13%. After adjustment for demographic characteristics, prevalent vascular disease (stroke, coronary artery disease, and peripheral arterial disease) and traditional vascular risk factors (diabetes, hypertension, smoking, and elevated cholesterol), an eGFR<30 ml/min per 1.73 m2 was associated with a 47% increased odds of cognitive impairment (odds ratio 1.47, 95% confidence interval 1.05, 2.05) relative to those with an eGFR 45 to 59 ml/min per 1.73 m2. This association was attenuated and no longer significant after adjustment for hemoglobin concentration. While other nontraditional vascular risk factors including C-reactive protein, homocysteine, serum albumin, and albuminuria were correlated with cognitive impairment in unadjusted analyses, they were not significantly associated with cognitive impairment after adjustment for eGFR and other confounders.The prevalence of cognitive impairment was higher among those with lower eGFR, independent of traditional vascular risk factors. This association may be explained in part by anemia.

  View details for DOI 10.2215/CJN.02660310

  View details for PubMedID 20930087

• Dementia and cognitive impairment in ESRD: diagnostic and therapeutic strategies KIDNEY INTERNATIONAL Tamura, M. K., Yaffe, K. 2011; 79 (1): 14-22

  Abstract

  Cognitive impairment, including dementia, is a common but poorly recognized problem among patients with end-stage renal disease (ESRD), affecting 16-38% of patients. Dementia is associated with high risks of death, dialysis withdrawal, hospitalization, and disability among patients with ESRD; thus, recognizing and effectively managing cognitive impairment may improve clinical care. Dementia screening strategies should take into account patient factors, the time available, the timing of assessments relative to dialysis treatments, and the implications of a positive screen for subsequent management (for example, transplantation). Additional diagnostic testing in patients with cognitive impairment, including neuroimaging, is largely based on the clinical evaluation. There is limited data on the efficacy and safety of pharmacotherapy for dementia in the setting of ESRD; therefore, decisions about the use of these medications should be individualized. Management of behavioral symptoms, evaluation of patient safety, and advance care planning are important components of dementia management. Prevention strategies targeting vascular risk factor modification, and physical and cognitive activity have shown promise in the general population and may be reasonably extrapolated to the ESRD population. Modification of ESRD-associated factors such as anemia and dialysis dose or frequency require further study before they can be recommended for treatment or prevention of cognitive impairment.

  View details for DOI 10.1038/ki.2010.336

  View details for Web of Science ID 000285334100004

  View details for PubMedCentralID PMC3107192

• Dementia and cognitive impairment in ESRD: diagnostic and therapeutic strategies. Kidney international Kurella Tamura, M., Yaffe, K. 2011; 79 (1): 14-22

  Abstract

  Cognitive impairment, including dementia, is a common but poorly recognized problem among patients with end-stage renal disease (ESRD), affecting 16-38% of patients. Dementia is associated with high risks of death, dialysis withdrawal, hospitalization, and disability among patients with ESRD; thus, recognizing and effectively managing cognitive impairment may improve clinical care. Dementia screening strategies should take into account patient factors, the time available, the timing of assessments relative to dialysis treatments, and the implications of a positive screen for subsequent management (for example, transplantation). Additional diagnostic testing in patients with cognitive impairment, including neuroimaging, is largely based on the clinical evaluation. There is limited data on the efficacy and safety of pharmacotherapy for dementia in the setting of ESRD; therefore, decisions about the use of these medications should be individualized. Management of behavioral symptoms, evaluation of patient safety, and advance care planning are important components of dementia management. Prevention strategies targeting vascular risk factor modification, and physical and cognitive activity have shown promise in the general population and may be reasonably extrapolated to the ESRD population. Modification of ESRD-associated factors such as anemia and dialysis dose or frequency require further study before they can be recommended for treatment or prevention of cognitive impairment.

  View details for DOI 10.1038/ki.2010.336

  View details for PubMedID 20861818

• Design and Rationale of Health-Related Quality of Life and Patient-Reported Outcomes Assessment in the Frequent Hemodialysis Network Trials 13th International Conference on Dialysis, Advances Jhamb, M., Tamura, M. K., Gassman, J., Garg, A. X., Lindsay, R. M., Suri, R. S., Ting, G., Finkelstein, F. O., Beach, S., Kimmel, P. L., Unruh, M. KARGER. 2011: 151–58

  Abstract

  End-stage renal disease patients experience significant impairments in health-related quality of life (HRQOL). Testing various strategies to improve patient HRQOL in multicenter clinical trials, such as the Frequent Hemodialysis Network (FHN) trials is vitally important.The aim of this paper is to describe the design and conduct of HRQOL and patient-reported outcomes (PRO) assessment in the FHN trials.In the FHN trials, HRQOL was examined as a multidimensional concept, and the SF-36 RAND Physical Health Composite score was one of the co-primary outcomes. The instruments completed to assess HRQOL included the Medical Outcomes Study Short Form SF-36, Health Utilities Index 3, Sleep Problems Index, Beck Depression Inventory and feeling thermometer. These instruments have been shown to have high reliability, validity and responsiveness to change in the end-stage renal disease population. Additional items evaluating PRO including sexual function, time to recovery after dialysis and patients' self-perceived burden to caregiver were also assessed. All questionnaires were administered by trained interviewers using computer-assisted telephone interviewing to ensure blinding and minimizing selection bias. Interim analysis reveals that these instruments can be used to collect a comprehensive set of HRQOL measures with minimal patient burden.Accurate measurement of HRQOL and PRO can help us test whether hemodialysis interventions improve the health and well-being of this compromised patient population. We have shown that a comprehensive set of HRQOL measures can be centrally collected through telephone interviews in a blinded fashion, in a way that is well tolerated with minimum respondent burden.

  View details for DOI 10.1159/000321855

  View details for Web of Science ID 000287667000026

  View details for PubMedID 21228584

  View details for PubMedCentralID PMC3202955

• The Association between Parathyroid Hormone Levels and the Cardiorenal Metabolic Syndrome in Non-Diabetic Chronic Kidney Disease CARDIORENAL MEDICINE Saab, G., Whaley-Connell, A., Bombeck, A., Tamura, M. K., Li, S., Chen, S., McFarlane, S. I., Sowers, J. R., Norris, K., Bakris, G. L., McCullough, P. A. 2011; 1 (2): 123-130

  Abstract

  The relationship between parathyroid hormone (PTH) and the cardiorenal metabolic syndrome was examined among non-diabetic persons with chronic kidney disease (CKD).In a cross-sectional analysis, the relationship between PTH levels and the cardiorenal metabolic syndrome was investigated in 3,215 non-diabetic participants in the National Kidney Foundation-Kidney Early Evaluation Program (KEEP 2.0) found to have CKD (eGFR <60 ml/min/1.73 m2).In unadjusted analyses, the prevalence of the cardiorenal metabolic syndrome increased along increasing PTH quartiles (31.7, 33.8, 37.3, and 48.7%, respectively, p for trend <0.0001). After multivariate adjustment, as compared to the first PTH quartile, odds of the cardiorenal metabolic syndrome were 16% (p = 0.18), 35% (p = 0.006), and 80% (p < 0.0001) higher for the second, third, and fourth quartiles, respectively. When taken as a continuous predictor, each standard deviation increase of natural log transformed PTH was associated with 26% (p < 0.0001) higher odds of the cardiorenal metabolic syndrome. The association of PTH with the cardiorenal metabolic syndrome was not modified by age or gender (p for interaction was not significant for both modifiers).Among an outpatient non-diabetic population with CKD, higher PTH levels were associated with a higher prevalence of the cardiorenal metabolic syndrome.

  View details for DOI 10.1159/000327149

  View details for Web of Science ID 000312167400006

  View details for PubMedCentralID PMC3101512

• Impact of Sleep Quality on Cardiovascular Outcomes in Hemodialysis Patients: Results from the Frequent Hemodialysis Network Study AMERICAN JOURNAL OF NEPHROLOGY Unruh, M., Tamura, M. K., Larive, B., Rastogi, A., James, S., Schiller, B., Gassman, J., Chan, C., Lockridge, R., Kliger, A. 2011; 33 (5): 398-406

  Abstract

  Poor sleep quality is a common, persistent, and important problem to patients with end-stage renal disease (ESRD). This report examines whether sleep quality is associated with dialysis treatment factors and other modifiable clinical factors in a large group of hemodialysis (HD) patients.Cross-sectional analyses were conducted on baseline data collected from participants in the Frequent Hemodialysis Network trials. Sleep quality was measured using the Medical Outcomes Study Sleep Problems Index II (SPI II), a 9-item measure of sleep quality with higher scores reflecting poorer sleep quality.The participants had an age of 51.2 ± 13.6 years, 61% were male, 38% were black, and 42% had diabetes. Higher pre-dialysis serum phosphorus (per 0.5 mg/ml) (OR 0.91; 95% CI 0.85, 0.96) and depression (OR 0.16; 95% CI 0.10, 0.25) were independently associated with decrements in sleep quality. There was also a difference in time to recovery from dialysis for the fourth versus the first SPI II quartile (5.1 h; p < 0.0001).These findings underscore the link between sleep and daytime function and suggest that improving sleep may provide an opportunity to improve outcomes in ESRD. Whether sleep problems may be improved by reduction of serum phosphorus or treatment of depression in the HD population merits further investigation.

  View details for DOI 10.1159/000326343

  View details for Web of Science ID 000290841100003

  View details for PubMedCentralID PMC3080580

• Signs and Symptoms Associated With Earlier Dialysis Initiation in Nursing Home Residents AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M. K., O'Hare, A. M., McCulloch, C. E., Johansen, K. L. 2010; 56 (6): 1117-1126

  Abstract

  Factors driving the trend of earlier dialysis initiation for persons with end-stage renal disease are unknown. We wanted to determine the association of the number and type of signs and symptoms with timing of initiation of dialysis in US nursing home residents.Observational study.We used data from the US Renal Data System linked with the Minimum Data Set, a national registry of nursing home residents. The cohort consisted of 2,402 nursing home residents who initiated dialysis between 1998 and 2000 and had at least 2 recorded clinical assessments in the year before dialysis initiation.We evaluated 7 clinical signs and symptoms: dependence in activities of daily living, cognitive function, edema, dyspnea, nutritional problems, vomiting, and body size.Earlier dialysis initiation was defined as estimated glomerular filtration rate ≥ 1 5 mL/min/1.73 m² at the start of dialysis.Median estimated glomerular filtration rate at the start of dialysis was 9.8 (25th-75th percentile, 7.4-13.4) mL/min/1.73 m². After adjustment for age, sex, race, and comorbid conditions, each additional sign or symptom was associated with a higher odds for earlier dialysis initiation (OR, 1.16 per symptom; 95% CI, 1.06-1.28), as was each adversely changing sign or symptom (OR, 1.26 per symptom; 95% CI, 1.16-1.38). The population-attributable risk for earlier dialysis initiation associated with having one or more signs and symptoms of volume overload, cognitive decline, increasing activities of daily living dependence, and weight loss was 31%; volume overload had the largest aggregate population-attributable risk.We lacked information about metabolic indications for dialysis initiation.Volume overload, cognitive decline, increasing activities of daily living dependence, and weight loss were associated with earlier dialysis initiation; however, these factors explained less than one-third of cases of earlier dialysis initiation in nursing home residents.

  View details for DOI 10.1053/j.ajkd.2010.08.017

  View details for Web of Science ID 000284401800016

  View details for PubMedID 20974509

  View details for PubMedCentralID PMC2991507

• Hemoglobin Concentration and Cognitive Impairment in the Renal REasons for Geographic And Racial Differences in Stroke (REGARDS) Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Kurella Tamura, M., Wadley, V. G., Newsome, B. B., Zakai, N. A., McClure, L. A., Howard, G., Warnock, D. G., McClellan, W. 2010; 65 (12): 1380-1386

  Abstract

  There is growing interest in determining the degree of anemia, which is clinically significant. The goal of this study was to determine the association between hemoglobin concentration and cognitive impairment in a large sample of U.S. adults.We used cross-sectional data from 19,701 adults participating in the REasons for Geographic And Racial Differences in Stroke study. Cognitive impairment was defined as a score of 4 or less on the six-item screener. Hemoglobin was analyzed in 1 g/dL increments relative to the World Health Organization (WHO) threshold (<13 g/dL for men and <12 g/dL for women).The mean hemoglobin concentration was 13.7 ± 1.5 g/dL. The prevalence of cognitive impairment increased from 4.3% among individuals with a hemoglobin >3 g/dL above the WHO threshold to 16.8% for those with a hemoglobin ≥2 g/dL below the WHO threshold. After adjustment for demographics, chronic health conditions, health status, and inflammation, the association between reduced hemoglobin and cognitive impairment was attenuated and no longer significant, including among those with hemoglobin ≥2 g/dL below the WHO threshold (odds ratio 1.39, 95% confidence interval = 0.94-2.04). A test for linear trend was of borderline significance (p value = .06). For 94% of the sample within 2 g/dL of the WHO threshold, there was no relationship between hemoglobin concentration and the odds of cognitive impairment. The associations did not differ by sex and race.Within a large sample of community-dwelling adults, there was no significant association between hemoglobin concentration and cognitive impairment after multivariable adjustment.

  View details for DOI 10.1093/gerona/glq126

  View details for Web of Science ID 000284639700014

  View details for PubMedID 20634281

  View details for PubMedCentralID PMC2990263

• Should there be an expanded role for palliative care in end-stage renal disease? CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Tamura, M. K., Cohen, L. M. 2010; 19 (6): 556-560

  Abstract

  In this review, we outline the rationale for expanding the role of palliative care in end-stage renal disease (ESRD), describe the components of a palliative care model, and identify potential barriers in implementation.Patients receiving chronic dialysis have reduced life expectancy and high rates of chronic pain, depression, cognitive impairment, and physical disability. Delivery of prognostic information and advance care planning are desired by patients, but occur infrequently. Furthermore, although hospice care is associated with improved symptom control and lower healthcare costs at the end of life, it is underutilized by the ESRD population, even among patients who withdraw from dialysis. A palliative care model incorporating communication of prognosis, advance care planning, symptom assessment and management, and timely hospice referral may improve quality of life and quality of dying. Resources and clinical practice guidelines are available to assist practitioners with incorporating palliative care into ESRD management.There is a large unmet need to alleviate the physical, psychosocial, and existential suffering of patients with ESRD. More fully integrating palliative care into ESRD management by improving end-of-life care training, eliminating structural and financial barriers to hospice use, and identifying optimal methods to deliver palliative care are necessary if we are to successfully address the needs of an aging ESRD population.

  View details for DOI 10.1097/MNH.0b013e32833d67bc

  View details for Web of Science ID 000282981200007

  View details for PubMedID 20644475

  View details for PubMedCentralID PMC3107069

• Prevalence and Correlates of Cognitive Impairment in Hemodialysis Patients: The Frequent Hemodialysis Network Trials CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Larive, B., Unruh, M. L., Stokes, J. B., Nissenson, A., Mehta, R. L., Chertow, G. M. 2010; 5 (8): 1429-1438

  Abstract

  Cognitive impairment is common among persons with ESRD, but the underlying mechanisms are unknown. This study evaluated the prevalence of cognitive impairment and association with modifiable ESRD- and dialysis-associated factors in a large group of hemodialysis patients.Cross-sectional analyses were conducted on baseline data collected from 383 subjects participating in the Frequent Hemodialysis Network trials. Global cognitive impairment was defined as a score <80 on the Modified Mini-Mental State Exam, and impaired executive function was defined as a score >or=300 seconds on the Trailmaking B test. Five main categories of explanatory variables were examined: urea clearance, nutritional markers, hemodynamic measures, anemia, and central nervous system (CNS)-active medications.Subjects had a mean age of 51.6 +/- 13.3 years and a median ESRD vintage of 2.6 years. Sixty-one subjects (16%) had global cognitive impairment, and 110 subjects (29%) had impaired executive function. In addition to several nonmodifiable factors, the use of H1-receptor antagonists and opioids were associated with impaired executive function. No strong association was found between several other potentially modifiable factors associated with ESRD and dialysis therapy, such as urea clearance, proxies of dietary protein intake and other nutritional markers, hemodynamic measures, and anemia with global cognition and executive function after adjustment for case-mix factors.Cognitive impairment, especially impaired executive function, is common among hemodialysis patients, but with the exception of CNS-active medications, is not strongly associated with several ESRD- and dialysis-associated factors.

  View details for DOI 10.2215/CJN.01090210

  View details for PubMedID 20576825

• The elderly patients on hemodialysis. Minerva urologica e nefrologica = The Italian journal of urology and nephrology Anand, S., Kurella Tamura, M., Chertow, G. M. 2010; 62 (1): 87-101

  Abstract

  Nephrologists care for an increasing number of elderly patients on hemodialysis. As such, an understanding of the overlap among complications of hemodialysis and geriatric syndromes is crucial. This article reviews hemodialysis management issues including vascular access, hypertension, anemia and bone and mineral disorders with an attention towards the distinct medical needs of the elderly. Key concepts of geriatrics frailty, dementia and palliative care are also discussed, as nephrologists frequently participate in decision-making directed toward balancing longevity, functional status and the burden of therapy.

  View details for PubMedID 20424572

• The elderly patients on hemodialysis MINERVA UROLOGICA E NEFROLOGICA Anand, S., Tamura, M. K., Chertow, G. M. 2010; 62 (1): 87-101

  Abstract

  Nephrologists care for an increasing number of elderly patients on hemodialysis. As such, an understanding of the overlap among complications of hemodialysis and geriatric syndromes is crucial. This article reviews hemodialysis management issues including vascular access, hypertension, anemia and bone and mineral disorders with an attention towards the distinct medical needs of the elderly. Key concepts of geriatrics frailty, dementia and palliative care are also discussed, as nephrologists frequently participate in decision-making directed toward balancing longevity, functional status and the burden of therapy.

  View details for Web of Science ID 000208661300008

• Functional Status of Elderly Adults Receiving Dialysis REPLY NEW ENGLAND JOURNAL OF MEDICINE Tamura, M. 2010; 362 (5): 469

  View details for Web of Science ID 000274193300021

• Chronic Kidney Disease and Cognitive Function in Older Adults: Findings from the Chronic Renal Insufficiency Cohort Cognitive Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Yaffe, K., Ackerson, L., Tamura, M. K., Le Blanc, P., Kusek, J. W., Sehgal, A. R., Cohen, D., Anderson, C., Appel, L., DeSalvo, K., Ojo, A., Seliger, S., Robinson, N., Makos, G., Go, A. S. 2010; 58 (2): 338-345

  Abstract

  To investigate cognitive impairment in older, ethnically diverse individuals with a broad range of kidney function, to evaluate a spectrum of cognitive domains, and to determine whether the relationship between chronic kidney disease (CKD) and cognitive function is independent of demographic and clinical factors.Cross-sectional.Chronic Renal Insufficiency Cohort Study.Eight hundred twenty-five adults aged 55 and older with CKD.Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2)) was estimated using the four-variable Modification of Diet in Renal Disease equation. Cognitive scores on six cognitive tests were compared across eGFR strata using linear regression; multivariable logistic regression was used to examine level of CKD and clinically significant cognitive impairment (score < or =1 standard deviations from the mean).Mean age of the participants was 64.9, 50.4% were male, and 44.5% were black. After multivariable adjustment, participants with lower eGFR had lower cognitive scores on most cognitive domains (P<.05). In addition, participants with advanced CKD (eGFR<30) were more likely to have clinically significant cognitive impairment on global cognition (adjusted odds ratio (AOR) 2.0, 95% CI=1.1-3.9), naming (AOR=1.9, 95% CI=1.0-3.3), attention (AOR=2.4, 95% CI=1.3-4.5), executive function (AOR=2.5, 95% CI=1.9-4.4), and delayed memory (AOR=1.5, 95% CI=0.9-2.6) but not on category fluency (AOR=1.1, 95% CI=0.6-2.0) than those with mild to moderate CKD (eGFR 45-59).In older adults with CKD, lower level of kidney function was associated with lower cognitive function on most domains. These results suggest that older patients with advanced CKD should be screened for cognitive impairment.

  View details for DOI 10.1111/j.1532-5415.2009.02670.x

  View details for Web of Science ID 000274183800017

  View details for PubMedID 20374407

  View details for PubMedCentralID PMC2852884

• Preferences for dialysis withdrawal and engagement in advance care planning within a diverse sample of dialysis patients NEPHROLOGY DIALYSIS TRANSPLANTATION Tamura, M. K., Goldstein, M. K., Perez-Stable, E. J. 2010; 25 (1): 237-242

  Abstract

  Rates of dialysis withdrawal are higher among the elderly and lower among Blacks, yet it is unknown whether preferences for withdrawal and engagement in advance care planning also vary by age and race or ethnicity. DESIGN, SETTING, PARTICIPANTS AND METHODS: We recruited 61 participants from two dialysis clinics to complete questionnaires regarding dialysis withdrawal preferences in five different health states. Engagement in advance care planning (end-of-life discussions), completion of advance directives and 'do not resuscitate' or 'do not intubate' (DNR/DNI) orders were ascertained by a questionnaire and from dialysis unit records.The mean age was 62 +/- 15 years; 38% were Black, 11% were Latino, 34% were White and 16% of participants were Asian. Blacks were less likely to prefer dialysis withdrawal as compared with Whites (odds ratio 0.16, 95% confidence interval 0.03-0.88) and other race/ethnicity groups, and this difference was not explained by age, education, comorbidity and other confounders. In contrast, older age was not associated with preferences for withdrawal. Rates of engagement in end-of-life discussions were higher than for documentation of advance care planning for all age and most race/ethnicity groups. Although younger participants and minorities were generally less likely to document treatment preferences as compared with older patients and Whites, they were not less likely to engage in end-of-life discussions.Preferences for withdrawal vary by race/ ethnicity, whereas the pattern of engagement in advance care planning varies by age and race/ethnicity. Knowledge of these differences may be useful for improving communication about end-of-life preferences and in implementing effective advance care planning strategies among diverse haemodialysis patients.

  View details for DOI 10.1093/ndt/gfp430

  View details for Web of Science ID 000273113100039

  View details for PubMedID 19734137

  View details for PubMedCentralID PMC2910327

• Cardiometabolic Syndrome CARDIORENAL SYNDROME: MECHANISMS, RISK AND TREATMENT Tamura, M., Chang, T. I., Berbari, A. E., Mancia, G. 2010: 131–44

  View details for DOI 10.1007/978-88-470-1463-3_10

  View details for Web of Science ID 000281864600010

• Frailty and Chronic Kidney Disease: The Third National Health and Nutrition Evaluation Survey AMERICAN JOURNAL OF MEDICINE Wilhelm-Leen, E. R., Hall, Y. N., Tamura, M. K., Chertow, G. M. 2009; 122 (7): 664-U86

  Abstract

  Frailty is common in the elderly and in persons with chronic diseases. Few studies have examined the association of frailty with chronic kidney disease.We used data from the Third National Health and Nutrition Examination Survey to estimate the prevalence of frailty among persons with chronic kidney disease. We created a definition of frailty based on established validated criteria, modified to accommodate available data. We used logistic regression to determine whether and to what degree stages of chronic kidney disease were associated with frailty. We also examined factors that might mediate the association between frailty and chronic kidney disease.The overall prevalence of frailty was 2.8%. However, among persons with moderate to severe chronic kidney disease (estimated glomerular filtration rate < 45 mL/min/1.73 m2), 20.9% were frail. The odds of frailty were significantly increased among all stages of chronic kidney disease, even after adjustment for the residual effects of age, sex, race, and prevalent chronic diseases. The odds of frailty associated with chronic kidney disease were only marginally attenuated with additional adjustment for sarcopenia, anemia, acidosis, inflammation, vitamin D deficiency, hypertension, and cardiovascular disease. Frailty and chronic kidney disease were independently associated with mortality.Frailty is significantly associated with all stages of chronic kidney disease and particularly with moderate to severe chronic kidney disease. Potential mechanisms underlying the chronic kidney disease and frailty connection remain elusive.

  View details for DOI 10.1016/j.amjmed.2009.01.026

  View details for PubMedID 19559169

• POST-TRANSPLANT HEMODIALYSIS DRASTICALLY REDUCES ONE-YEAR SURVIVAL IN PATIENTS ENTERING LIVER TRANSPLANTATION WITHOUT RENAL DYSFUNCTION 15th Annual Congress of the International-Liver-Transplantation-Society Ma, M., Brennan, T., Reyes, I., Tamura, M., Feng, S. WILEY-BLACKWELL. 2009: S156–S156

  View details for Web of Science ID 000267792300280

• Incidence, management, and outcomes of end-stage renal disease in the elderly CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Tamura, M. K. 2009; 18 (3): 252-257

  Abstract

  The elderly constitute a substantial and growing fraction of the end-stage renal disease (ESRD) population. We review recent studies on ESRD incidence, management, and outcomes in the elderly.Rates of treated ESRD among the elderly (>80 years) have risen by more than 50% in the last decade. In studies with a large number of elderly patients, median survival after dialysis initiation is modest, and although a majority have reasonable life expectancy, a substantial minority of elderly patients experience very high early mortality rates after dialysis initiation. Quality of life results are mixed--compared with younger ESRD patients or non-ESRD elderly, mental well being is similar and physical well being is reduced in elderly patients with ESRD. In several studies, elderly patients with ESRD initiating peritoneal dialysis had higher mortality rates than elderly patients with ESRD initiating hemodialysis. Strategies such as nondialytic management of ESRD or dietary protein restriction and delayed dialysis initiation may be alternatives for elderly patients wishing to avoid dialysis initiation, but further studies are needed to determine the patients best suited for these approaches. Quality improvement initiatives in geriatric ESRD care have been successfully implemented in some centers and may ultimately improve care for elderly patients with ESRD.These findings should help to clarify some of the risks and benefits of dialysis in the elderly and may be useful in dialysis decision-making and management.

  View details for DOI 10.1097/MNH.0b013e328326f3ac

  View details for Web of Science ID 000265560600011

  View details for PubMedID 19374012

  View details for PubMedCentralID PMC2738843

• Post-Transplant Hemodialysis Drastically Reduces One-Year Survival in Patients Entering Liver Transplantation without Renal Dysfunction. 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantation Ma, M., Brennan, T., Reyes, I., Tamura, M., Feng, S. WILEY-BLACKWELL. 2009: 261–261

  View details for Web of Science ID 000265068800245

• Kidney function and cognitive impairment in US adults: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M. K., Wadley, V., Yaffe, K., McClure, L. A., Howard, G., Go, R., Allman, R. M., Warnock, D. G., McClellan, W. 2008; 52 (2): 227-234

  Abstract

  The association between kidney function and cognitive impairment has not been assessed in a national sample with a wide spectrum of kidney disease severity.Cross-sectional.23,405 participants (mean age, 64.9 +/- 9.6 years) with baseline measurements of creatinine and cognitive function participating in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a study of stroke risk factors in a large national sample.Estimated glomerular filtration rate (eGFR).Cognitive impairment.Chronic kidney disease (CKD) was defined as eGFR less than 60 mL/min/1.73 m(2). Kidney function was analyzed in 10-mL/min/1.73 m(2) increments in those with CKD, and in exploratory analyses, across the range of kidney function. Cognitive function was assessed using the 6-Item Screener, and participants with a score of 4 or less were considered to have cognitive impairment.CKD was associated with an increased prevalence of cognitive impairment independent of confounding factors (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.43). In patients with CKD, each 10-mL/min/1.73 m(2) decrease in eGFR less than 60 mL/min/1.73 m(2) was associated with an 11% increased prevalence of impairment (odds ratio, 1.11; 95% confidence interval, 1.04 to 1.19). Exploratory analyses showed a nonlinear association between eGFR and prevalence of cognitive impairment, with a significant increased prevalence of impairment in those with eGFR less than 50 and 100 mL/min/1.73 m(2) or greater.Longitudinal measures of cognitive function were not available.In US adults, lower levels of kidney function are associated with an increased prevalence of cognitive impairment. The prevalence of impairment appears to increase early in the course of kidney disease; therefore, screening for impairment should be considered in all adults with CKD.

  View details for DOI 10.1053/j.ajkd.2008.05.004

  View details for Web of Science ID 000257943400007

  View details for PubMedID 18585836

  View details for PubMedCentralID PMC2593146

• Cystatin C as a marker of cognitive function in elders: Findings from the Health ABC study ANNALS OF NEUROLOGY Yaffe, K., Lindquist, K., Shlipak, M. G., Simonsick, E., Fried, L., Rosano, C., Satterfield, S., Atkinson, H., Windham, B. G., Kurella-Tamura, M. 2008; 63 (6): 798-802

  Abstract

  We determined whether serum cystatin C, a novel measure of kidney function that colocalizes with brain beta-amyloid, is associated with cognition among 3,030 elders. Those with high cystatin C (n = 445; 15%) had worse baseline scores on Modified Mini-Mental State Examination or Digit Symbol Substitution Test (p or=1.0 standard deviation) was greatest among those with high cystatin C (Modified Mini-Mental State Examination: 38 vs 25%; adjusted odds ratio, 1.92; 95% confidence interval, 1.37-2.69; Digit Symbol Substitution: 38 vs 26%; odds ratio, 1.54; 95% confidence interval, 1.10-2.15).

  View details for DOI 10.1002/ana.21383

  View details for Web of Science ID 000257294100014

  View details for PubMedID 18496846

  View details for PubMedCentralID PMC2584446

• Kidney function as a predictor of loss of lean mass in older adults: Health, aging and body composition study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Fried, L. F., Boudreau, R., Lee, J. S., Chertow, G., Kurella-Tamura, M., Shlipak, M. G., Ding, J., Sellmeyer, D., Tylavsky, F. A., Simsonick, E., Kritchevsky, S. B., Harris, T. B., Newman, A. B. 2007; 55 (10): 1578-1584

  Abstract

  To assess the association between kidney function and change in body composition in older individuals.Prospective cohort study.Two sites, Pittsburgh, Pennsylvania, and Memphis, Tennessee.Three thousand twenty-six well-functioning, participants aged 70 to 79 in the Health, Aging and Body Composition Study.Body composition (bone-free lean mass and fat mass) was measured using dual x-ray absorptiometry annually for 4 years. Kidney function was measured at baseline according to serum creatinine (SCr). Comorbidity and inflammatory markers were evaluated as covariates in mixed-model, repeated-measures analysis.High SCr was associated with loss of lean mass in men but not women, with a stronger relationship in black men (P=.02 for difference between slopes for white and black men). In white men, after adjustment for age and comorbidity, higher SCr remained associated with loss of lean mass (-0.07+/-0.03 kg/y greater loss per 0.4 mg/dL (1 standard deviation (SD)), P=.009) but was attenuated after adjustment for inflammatory factors (-0.05+/-0.03 kg/y greater loss per SD, P=.10). In black men, the relationship between SCr and loss of lean mass (-0.19+/-0.04 kg/y per SD, P<.001) persisted after adjustment for inflammation and overall weight change.Impaired kidney function may contribute to loss of lean mass in older men. Inflammation appeared to mediate the relationship in white but not black men. Future studies should strive to elucidate mechanisms linking kidney disease and muscle loss and identify treatments to minimize loss of lean mass and its functional consequences.

  View details for DOI 10.1111/j.1532-5415.2007.01398.x

  View details for Web of Science ID 000249825500011

  View details for PubMedID 17908060

• Correlates and outcomes of dementia among dialysis patients: the Dialysis Outcomes and Practice Patterns Study NEPHROLOGY DIALYSIS TRANSPLANTATION Kurella, M., Mapes, D. L., Port, F. K., Chertow, G. M. 2006; 21 (9): 2543-2548

  Abstract

  Recent studies suggest a high prevalence of cognitive impairment and dementia in persons with end-stage renal disease (ESRD), yet risk factors for dementia and its prognostic significance in persons with ESRD remain unclear. The goals of this study were to determine the prevalence, correlates and dialysis-related outcomes of dementia in an international sample of haemodialysis patients.We analysed data collected from a cohort of 16 694 patients in the Dialysis Outcomes and Practice Patterns Study. Dementia was defined as a diagnosis of dementia documented in the medical record. We used logistic regression to determine the baseline correlates of dementia and Cox proportional hazards models to determine the relative risk (RR) of death and dialysis withdrawal for patients with dementia, while adjusting for a number of confounding factors.Overall, 4% of the cohort had a recorded diagnosis of dementia. In the cross-sectional analyses, risk factors for dementia in the general population including age, black race, low educational attainment, cerebrovascular disease and diabetes, as well as modifiable uraemia-related factors, including markers of malnutrition and anaemia, were independently associated with dementia. After adjustment for a number of confounding factors, dementia was associated with an increased risk of death [RR 1.48, 95% confidence interval (CI) 1.32-1.66] and dialysis withdrawal (RR 2.01, 95% CI 1.57-2.57).Dementia is associated with adverse outcomes among ESRD patients. Dialysis providers should consider instituting routine screening for cognitive impairment among elderly patients in order to identify those at risk for associated adverse outcomes.

  View details for DOI 10.1093/ndt/gfl275

  View details for Web of Science ID 000240694200032

  View details for PubMedID 16751655

• The tortoise and hare on hemodialysis: Does slow and steady win the race? KIDNEY INTERNATIONAL Chertow, G. M., Kurella, M., Lowrie, E. G. 2006; 70 (1): 24-25

  Abstract

  The importance of hemodialysis session length relative to small solute (e.g., urea) clearance has been debated for many years. Longer session length augments clearance of larger molecules and may facilitate ultrafiltration; however, the independent effects of session length on survival and other outcomes are unknown. In this report, we review two recently published observational studies examining the association between hemodialysis session length and survival. Prospective clinical trials will be required to resolve the debate.

  View details for DOI 10.1038/sj.ki.5001544

  View details for Web of Science ID 000238969300012

  View details for PubMedID 16763569

• The metabolic syndrome and chronic kidney disease CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Peralta, C. A., Kurella, M., Lo, J. C., Chertow, G. M. 2006; 15 (4): 361-365

  Abstract

  The metabolic syndrome is a constellation of physical and laboratory abnormalities including hypertension, hyperglycemia, hyperlipidemia and abdominal obesity. Over the past decade, the metabolic syndrome has emerged as a critically important risk factor for cardiovascular disease.A large population-based cross-sectional analysis (the National Health and Nutrition Evaluation Survey III) found that the presence of the metabolic syndrome was associated with chronic kidney disease, defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m and was also associated with proteinuria. More recently, a prospective cohort study found that the presence of the metabolic syndrome was associated with incident chronic kidney disease by the same definition, even when excluding individuals with diabetes mellitus and hypertension. More studies are required to determine whether the relationship between the metabolic syndrome and chronic kidney disease is mainly mediated by hyperglycemia (with insulin resistance) and hypertension, or other metabolic or hemodynamic factors.The metabolic syndrome is associated with chronic kidney disease. Efforts aimed at determining the mechanisms underlying this association and strategies for the prevention of chronic kidney disease (or slowing the progression of chronic kidney disease) in affected patients should be research priorities in the future.

  View details for Web of Science ID 000239103000002

  View details for PubMedID 16775449

• Systemic inflammatory markers, periodontal diseases, and periodontal infections in an elderly population JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Bretz, W. A., Weyant, R. J., Corby, P. M., Ren, D., Weissfeld, L., Kritchevsky, S. B., Harris, T., Kurella, M., Satterfield, S., Visser, M., Newman, A. B. 2005; 53 (9): 1532-1537

  Abstract

  To study the levels of systemic markers for inflammation with parameters of periodontal diseases in older people.A cross-sectional study was conducted in a cohort that is being followed prospectively on the effects of aging and body composition on morbidity.University of Pittsburgh, Pittsburgh, and University of Tennessee, Memphis.One thousand one hundred thirty-one participants (mean age+/-standard deviation 72.7+/-2.8); 66% white and 50% male.Periodontal examination, including probing depth and attachment loss, was performed. Periodontal disease extent was divided into 0% of sites with probing depth of 6 mm or more, 1% to 10% of sites with probing depth of 6 mm or more and more than 10% of sites with probing depth of 6 mm or more. Subgingival plaque samples were collected from four molar teeth, and the levels of periodontal pathogens were determined using the benzoyl-DL-arginine-naphthylamide (BANA) test. Plasma interleukin-6 (IL-6), C-reactive protein (CRP), plasminogen activator inhibitor type-1 (PAI-1), and tumor necrosis factor alpha (TNF-alpha) levels were measured in all participants. Assessments of risk factors associated with elevated levels of markers of systemic inflammation were also determined. Multiple regression analysis was employed to analyze the data.IL-6 levels were significantly higher in participants with more-extensive periodontal disease than in other participants. Periodontal disease extent was significantly associated with higher TNF-alpha plasma levels, controlling for established risk factors for elevated TNF-alpha levels. Participants with BANA-positive species had significantly higher CRP plasma levels when controlling for risk factors for elevated CRP levels.Periodontal disease and infection may be modifiable risk indicators for elevated levels of systemic inflammatory markers in older people.

  View details for DOI 10.1111/j.1532-5415.2005.53468.x

  View details for Web of Science ID 000231509000012

  View details for PubMedID 16137283

• Chronic kidney disease and cognitive impairment in the elderly: The health, aging, and body composition study JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kurella, M., Chertow, G. M., Fried, L. F., Cummings, S. R., Harris, T., Simonsick, E., Satterfield, S., Ayonayon, H., Yaffe, K. 2005; 16 (7): 2127-2133

  Abstract

  Previous studies suggest a link between chronic kidney disease (CKD) and cognitive impairment. Whether the longitudinal course of cognitive impairment differs among people with or without CKD is unknown. Data collected in 3034 elderly individuals who participated in the Health, Aging, and Body Composition study were analyzed. Cognitive function was assessed with the Modified Mini-Mental State Exam (3MS) at baseline and then 2 and 4 yr after baseline. Cognitive impairment was defined as a 3MS score <80 or a decline in 3MS >5 points after 2 or 4 yr of follow-up among participants with baseline 3MS scores > or =80. Participants with CKD, defined as an estimated GFR (eGFR) <60 ml/min per 1.73 m2, were further divided into two eGFR strata. Unadjusted mean baseline 3MS scores and mean declines in 3MS scores over 4 yr were significantly more pronounced for participants with lower baseline eGFR. More advanced stages of CKD were associated with an increased risk for cognitive impairment: Odds ratio (OR) 1.32 (95% confidence interval [CI] 1.03 to 1.69) and OR 2.43 (95% CI, 1.38 to 4.29) for eGFR 45 to 59 ml/min per 1.73 m2 and <45 ml/min per 1.73 m2, respectively, adjusted for case mix, baseline 3MS scores, and other potential confounders. CKD is associated with an increased risk for cognitive impairment in the elderly that cannot be fully explained by other well-established risk factors. Studies aimed at understanding the mechanism(s) responsible for cognitive impairment in CKD and efforts to interrupt this decline are warranted.

  View details for Web of Science ID 000230046900032

  View details for PubMedID 15888561

• Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kurella, M., Lo, J. C., Chertow, G. M. 2005; 16 (7): 2134-2140

  Abstract

  The metabolic syndrome is a risk factor for the development of diabetes and cardiovascular disease; however, no prospective studies have examined the metabolic syndrome as a risk factor for chronic kidney disease (CKD). A total of 10,096 nondiabetic participants who were in the Atherosclerosis Risk in Communities study and had normal baseline kidney function composed the study cohort. The metabolic syndrome was defined according to recent guidelines from the National Cholesterol Education Program. Incident CKD was defined as an estimated GFR (eGFR) <60 ml/min per 1.73 m2 at study year 9 among those with an eGFR > or =60 ml/min per 1.73 m2 at baseline. After 9 yr of follow-up, 691 (7%) participants developed CKD. The multivariable adjusted odds ratio (OR) of developing CKD in participants with the metabolic syndrome was 1.43 (95% confidence interval [CI], 1.18 to 1.73). Compared with participants with no traits of the metabolic syndrome, those with one, two, three, four, or five traits of the metabolic syndrome had OR of CKD of 1.13 (95% CI, 0.89 to 1.45), 1.53 (95% CI, 1.18 to 1.98), 1.75 (95% CI, 1.32 to 2.33), 1.84 (95% CI, 1.27 to 2.67), and 2.45 (95% CI, 1.32 to 4.54), respectively. After adjusting for the subsequent development of diabetes and hypertension during the 9 yr of follow-up, the OR of incident CKD among participants with the metabolic syndrome was 1.24 (95% CI, 1.01 to 1.51). The metabolic syndrome is independently associated with an increased risk for incident CKD in nondiabetic adults.

  View details for Web of Science ID 000230046900033

  View details for PubMedID 15901764

• Dialysis session length ("t") as a determinant of the adequacy of dialysis SEMINARS IN NEPHROLOGY Kurella, M., Chertow, G. M. 2005; 25 (2): 90-95

  Abstract

  Several studies have shown an association between the hemodialysis session length (the t of Kt or Kt/V) and favorable outcomes for patients on maintenance hemodialysis. In a single randomized controlled trial that systematically varied hemodialysis session length, shorter session length was associated with an increased risk for morbidity and mortality, independent of the time-averaged concentration of urea. Observational studies of dialysis session length have yielded conflicting results, although virtually all studies have confounded hemodialysis session length with hemodialysis efficiency or dose. Limited observational data from nocturnal hemodialysis programs more strongly suggest an independent beneficial effect of longer session length. In aggregate, data on the effects of hemodialysis session length are inconclusive. Future studies should evaluate hemodialysis session length independent of efficiency, and should consider the evaluation of dose by using other clearance parameters and the adequacy of ultrafiltration in addition to solute kinetics.

  View details for DOI 10.1016/j.semnephrol.2004.09.015

  View details for Web of Science ID 000228545200005

  View details for PubMedID 15791560

• Suicide in the United States end-stage renal disease program JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kurella, M., Kimmel, P. L., Young, B. S., Chertow, G. M. 2005; 16 (3): 774-781

  Abstract

  Although depression and dialysis withdrawal are relatively common among individuals with ESRD, there have been few systematic studies of suicide in this population. The goals of this study were to compare the incidence of suicide with national rates and to contrast the factors associated with suicide with those associated with withdrawal in persons with ESRD. All individuals who were aged 15 yr and older and initiated dialysis between April 1, 1995, and November 30, 2000, composed the analytic cohort. Patients were censored at the time of death, transplantation, or October 31, 2001. Death as a result of suicide in the ESRD population and the general US population was ascertained from the Death Notification Form and the Centers for Disease Control and Prevention, respectively. Standardized incidence ratios for suicide among patient subgroups were computed using national data from the year 2000 as the reference population. The crude suicide rate from 1995 to 2001 was 24.2 suicides per 100,000 patient-years, and the overall standardized incidence ratio for suicide was 1.84 (95% confidence interval, 1.50 to 2.27). In multivariable models, age > or =75 yr, male gender, white or Asian race, geographic region, alcohol or drug dependence, and recent hospitalization with mental illness were significant independent predictors of death as a result of suicide. Persons with ESRD are significantly more likely to commit suicide than persons in the general population. Although relatively rare, risk assessment can be used to identify patients for whom counseling and other interventions might be beneficial.

  View details for DOI 10.1681/ASN.2004070550

  View details for Web of Science ID 000227372000026

  View details for PubMedID 15659561

• Frequent hemodialysis and psychosocial function SEMINARS IN DIALYSIS Kurella, M., Suri, R. S., Chertow, G. M. 2005; 18 (2): 132-136

  Abstract

  Studies suggest that more frequent hemodialysis (HD; short daily and long nocturnal dialysis) may be associated with a variety of clinical benefits, including improvement in blood pressure, anemia, and hyperphosphatemia, regression of left ventricular hypertrophy, and reduced rates of hospitalization. Whether these clinical benefits are paralleled by improvements in health-related quality of life (HRQOL) has been unclear. In addition, the psychosocial burden of more intensive HD schedules has not been critically evaluated. Recent reports have suggested beneficial effects of frequent HD on global HRQOL, dialysis-related and uremic symptoms, patient satisfaction, and psychosocial burden. However, the interpretation of many of these studies is restricted by limitations in study design, follow-up, and generalizability. This article reviews the current literature focusing on psychosocial and HRQOL effects of frequent HD and suggests future directions for research in this important area.

  View details for Web of Science ID 000227478200010

  View details for PubMedID 15771657

• Self-assessed sleep quality in chronic kidney disease. International urology and nephrology Kurella, M., Luan, J., Lash, J. P., Chertow, G. M. 2005; 37 (1): 159-165

  Abstract

  Although sleep complaints are commonly reported in persons with end stage renal disease (ESRD), little is known about the prevalence of sleep complaints in chronic kidney disease (CKD), and the relation of sleep quality to the severity of kidney disease.We administered the Kidney Disease Quality of Life (KDQOL) sleep scale to 156 subjects, 78 with ESRD and 78 with CKD. Glomerular filtration rate (GFR) was estimated using the six variable Modification of Diet in Renal Disease (MDRD) equation and used to stratify subjects with CKD as mild-moderate (GFR >25 ml/min/1.73 m(2)) and advanced (GFR <25 ml/min/1.73 m(2)). We used multivariable linear regression to determine independent predictors of KDQOL sleep scale scores. Higher scores indicate higher self-reported quality of sleep.Median scores on the KDQOL sleep scale were 59 (interquartile range 40-80) in subjects with ESRD and 69 (interquartile range 53-80) in subjects with CKD (P=0.04). Thirty-four percent of subjects with ESRD, 27% of subjects with advanced CKD, and 14% of subjects with mild to moderate CKD had sleep maintenance disturbances (P=0.05). Thirteen percent of subjects with ESRD, 11% of subjects with advanced CKD, and no subjects with mild-moderate CKD had complaints of daytime somnolence (P=0.03). There was no significant difference in the prevalence of sleep adequacy complaints in persons with ESRD versus CKD. In multivariable analyses, only age and ESRD status (vs. CKD) were significant predictors of lower KDQOL sleep scores. Among subjects with CKD, there was a significant direct association between estimated GFR and scores on the KDQOL sleep scale in non-African American subjects (P=0.01).Sleep complaints are common in persons with CKD and ESRD and may be associated with the severity of kidney disease.

  View details for PubMedID 16132780

• Chronic kidney disease and cognitive impairment in menopausal women AMERICAN JOURNAL OF KIDNEY DISEASES Kurella, M., Yaffe, K., Shlipak, M. G., Wenger, N. K., Chertow, G. M. 2005; 45 (1): 66-76

  Abstract

  Although end-stage renal disease has been associated with cognitive impairment, the relation between lesser degrees of chronic kidney disease (CKD) and cognitive impairment is less well understood.Data for 1,015 women enrolled at 10 of the 20 Heart Estrogen/Progestin Replacement Study clinical sites were analyzed. All participants were younger than 80 years and had established coronary artery disease at study entry. Participants underwent 6 standard tests of cognitive function evaluating various domains. Unadjusted, residual age- and race-adjusted, and multivariable-adjusted linear and logistic regression models were used. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease regression equation. In addition to analyses across the spectrum of GFRs, CKD was categorized as mild (estimated GFR [eGFR], 45 to 60 mL/min/1.73 m2), moderate (eGFR, 30 to 44 mL/min/1.73 m2), and severe (eGFR, <30 mL/min/1.73 m2) according to a modification of recently established classification guidelines.Mean eGFR was 57 +/- 14 mL/min/1.73 m2. In multivariable analyses, eGFR was associated significantly with impairment in global cognition, executive function, language, and memory (approximately 15% to 25% increase in risk for dysfunction/10-mL/min/1.73 m2 decrement in eGFR). Associations among eGFR and cognitive function were independent of residual effects of age and race (2 key determinants of GFR) and the contributions of education, lifestyle factors, stroke, diabetes, and other laboratory variables.CKD is associated with cognitive impairment in menopausal women with coronary artery disease.

  View details for DOI 10.1053/j.ajkd.2004.08.044

  View details for Web of Science ID 000226517300009

  View details for PubMedID 15696445

• Validation of the kidney disease quality of life (KDQOL) cognitive function subscale KIDNEY INTERNATIONAL Kurella, M., Luan, J., Yaffe, K., Chertow, G. M. 2004; 66 (6): 2361-2367

  Abstract

  Formal cognitive function testing is cumbersome, and no self-administered instruments for estimating cognitive function in persons with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been validated. The goal of this study was to determine the validity of the Kidney Disease Quality of Life Cognitive Function scale (KDQOL-CF) for the assessment of cognitive impairment in persons with kidney disease.We administered the KDQOL-CF to 157 subjects, 79 with ESRD and 78 with CKD participating in a cross-sectional study of cognitive function. Scores on the Modified Mini-Mental State Exam (3MS) were considered the gold standard measure of global cognitive function. Performance characteristics of the KDQOL-CF were assessed using correlation coefficients, Bland-Altman plots, and receiver operating characteristic curves.Median scores on the KDQOL-CF were 73 (interquartile range 60-87) for subjects with ESRD and 87 (interquartile range 73-100) for subjects with CKD (P < 0.0001). Scores on the KDQOL-CF were directly correlated with scores on the 3MS (r = 0.31, P = 0.0001). Defining global cognitive impairment as a 3MS score < 80, a cut-point of 60 on the KDQOL-CF accurately classified 76% of subjects, with 52% sensitivity and 81% specificity. On multivariable analysis, cerebral and peripheral vascular disease, benzodiazepine use, and higher serum phosphorus concentrations were associated with lower KDQOL-CF scores, while beta blocker use, education, and higher serum albumin concentrations were associated with higher KDQOL-CF scores.The KDQOL-CF is a valid instrument for estimating cognitive function in patients with CKD and ESRD. KDQOL-CF screening followed by 3MS testing in selected individuals may prove to be an effective and efficient strategy for identifying cognitive impairment in patients with kidney disease.

  View details for Web of Science ID 000225026200028

  View details for PubMedID 15569327

• Cognitive impairment in chronic kidney disease JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Kurella, M., Chertow, G. M., Luan, J., Yaffe, K. 2004; 52 (11): 1863-1869

  Abstract

  To assess the prevalence of cognitive impairment in persons with chronic kidney disease (CKD) and its relation to the severity of CKD.Cross-sectional study.University-affiliated ambulatory nephrology and dialysis practices.Eighty subjects with CKD Stages III and IV not requiring dialysis (CKD) and 80 subjects with CKD Stage V on hemodialysis (end-stage renal disease (ESRD)) with a mean age+/-standard deviation of 62.5+/-14.3.Three standardized cognitive tests, the Modified Mini-Mental State Examination (3MS), Trailmaking Test B (Trails B), and California Verbal Learning Trial (CVLT). Glomerular filtration rate was estimated in subjects with CKD using the six-variable Modification of Diet in Renal Disease equation.There was a graded relation between cognitive function and severity of CKD. Mean scores on the 3MS, Trails B, and CVLT immediate and delayed recall were significantly worse for subjects with ESRD than for subjects with CKD or published norms (P<.001 for all comparisons). Scores on the Trails B (P<.001) and CVLT immediate (P=.01) and delayed (P<.001) recall were significantly worse for subjects with CKD not requiring dialysis than for published norms. In addition, the fraction of subjects with impairment on the 3MS and Trails B increased with decreasing kidney function.Cognitive impairment is associated with the severity of kidney disease. Further studies are needed to determine the reasons for cognitive impairment in subjects with CKD and ESRD.

  View details for Web of Science ID 000224594100010

  View details for PubMedID 15507063

• Physical and sexual function in women with chronic kidney disease AMERICAN JOURNAL OF KIDNEY DISEASES Kurella, M., Ireland, C., Hlatky, M. A., Shlipak, M. G., Yaffe, K., Hulley, S. B., Chertow, G. M. 2004; 43 (5): 868-876

  Abstract

  Cross-sectional studies suggest an association between functional status and chronic kidney disease (CKD). Whether physical function deteriorates with progression of CKD is unknown.To determine associations among CKD, physical function, and sexual function in women, we conducted cross-sectional and longitudinal analyses of 2,761 women enrolled in the Heart and Estrogen/Progestin Replacement Study. Physical and sexual function were evaluated using the Duke Activity Status Index (DASI) and the Sexual Problems Scale of the Medical Outcomes Study, respectively. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease regression equation. In addition to analyses across the spectrum of GFR, CKD was categorized as mild (estimated GFR, 45 to 60 mL/min/1.73 m2), moderate (estimated GFR, 30 to 44 mL/min/1.73 m2), and severe (estimated GFR, <30 mL/min/1.73 m2) according to a modification of recently established classification guidelines.Mean age of study participants was 67 +/- 7 years, and mean estimated GFR was 61 +/- 14 mL/min/1.73 m2. In unadjusted analyses, mean baseline DASI score was 10 points lower in women with an estimated GFR less than 30 mL/min/1.73 m2 than in women with an estimated GFR of 60 mL/min/1.73 m2 or greater (P < 0.0001). Estimated GFR remained significantly associated with DASI score after multivariable adjustment. In longitudinal analyses, a decline in estimated GFR was associated with a significant decline in DASI score independent of baseline estimated GFR and other factors. There were no significant associations between estimated GFR and psychosocial aspects of sexual function.CKD is associated with impaired physical function, and a decline in estimated GFR is associated with a decline in physical function.

  View details for DOI 10.1053/j.ajkd.2003.12.050

  View details for Web of Science ID 000221104800013

  View details for PubMedID 15112178

• Correlates of executive function and memory in chronic kidney disease. Kurella, M., Luan, J., Yaffe, K., Chertow, G. M. LIPPINCOTT WILLIAMS & WILKINS. 2003: 846A

  View details for Web of Science ID 000186219103899

• Correlates of global cognitive function in chronic kidney disease. Kurella, M., Luan, J., Yaffe, K., Chertow, G. M. LIPPINCOTT WILLIAMS & WILKINS. 2003: 710A

  View details for Web of Science ID 000186219103276

• Analgesia in patients with ESRD: A review of available evidence AMERICAN JOURNAL OF KIDNEY DISEASES Kurella, M., Bennett, W. M., Chertow, G. M. 2003; 42 (2): 217-228

  Abstract

  Moderate to severe pain frequently accompanies chronic diseases in general and end-stage renal disease (ESRD) in particular. Several analgesic agents and associated metabolites show altered pharmacokinetics in the presence of reduced glomerular filtration rate. Drug-related side effects may exacerbate symptoms frequently observed in persons with chronic kidney disease (CKD; eg, fatigue, nausea, vomiting, and constipation) or those often attributed to hemodialysis therapy (eg, orthostatic hypotension and impaired cognition). Persons with advanced CKD and ESRD are at increased risk for adverse effects of analgesic agents because of enhanced drug sensitivity, comorbid conditions, and concurrent medication use. Dose adjustment and avoidance of certain analgesics may be required in patients with advanced CKD and ESRD. We review the available evidence on pharmacokinetics and adverse drug effects of various analgesic agents commonly used in patients with advanced CKD and ESRD. Determining an optimal approach to the control of pain in patients with advanced CKD and ESRD will require additional research.

  View details for DOI 10.1016/S0272-6386(03)00645-0

  View details for Web of Science ID 000184557300001

  View details for PubMedID 12900801

• Post transplant erythrocytosis in hypercalcernic renal transplant recipients AMERICAN JOURNAL OF TRANSPLANTATION Kurella, M., Butterly, D. W., Smith, S. R. 2003; 3 (7): 873-877

  Abstract

  In vitro data suggest that calcium plays an important role in normal and disordered erythropoiesis. The purpose of this study is to determine whether there is an association between serum calcium, various hormone levels, and the development of post transplant erythrocytosis (PTE). Data were collected on 283 patients who underwent renal transplantation between 1994 and 1998. The relationship between serum calcium and PTE development was tested using the chi-square test. Univariate and multivariable adjusted models were employed to determine predictors of maximum hematocrit. Selected patients underwent measurement of intact parathyroid hormone (PTH), 1,25-dihydroxy vitamin D, and erythropoietin (EPO). Seventy-three patients (26%) developed PTE. Post transplant erythrocytosis was more common in patients with hypercalcemia compared with patients with normal serum calcium (34% vs. 18%, p = 0.002). In multivariable analyses, serum calcium was a strong independent predictor of maximum hematocrit post transplant, even after adjustment for renal function. A serum calcium of >or=10.2 mg/dL was associated with greater than two-fold increased odds of PTE. There were no differences in hormone levels between subjects with hypercalcemia and PTE, subjects with PTE alone, and subjects with hypercalcemia alone. Hypercalcemia is associated with the development of PTE in renal transplant recipients.

  View details for Web of Science ID 000184032600013

  View details for PubMedID 12814479

• Intermittent nocturnal in-center hemodialysis: UCSF-Mt Zion experience. Kurella, M., Hung, A. M., Tichy, M., Hsu, C. Y., Chertow, G. M. AMER SOC NEPHROLOGY. 2002: 410A

  View details for Web of Science ID 000177757502021

• Monitoring changes in gene expression in renal ischemia-reperfusion in the rat KIDNEY INTERNATIONAL Yoshida, T., Kurella, M., Beato, F., Min, H., Ingelfinger, J. R., Stears, R. L., Swinford, R. D., Gullans, S. R., Tang, S. S. 2002; 61 (5): 1646-1654

  Abstract

  Although acute renal failure (ARF) is a relatively common disorder with major morbidity and mortality, its molecular basis remains incompletely defined. The present study examined global gene expression in the well-characterized ischemia-reperfusion model of ARF using DNA microarray technology.Male Wistar rats underwent bilateral renal ischemia (30 min) or sham operation, followed by reperfusion for 1, 2, 3 or 4 days. Plasma creatinine increased approximately fivefold over baseline, peaking on day 1. Renal total RNA was used to probe cDNA microarrays.Alterations in expression of 18 genes were identified by microarray analysis. Nine genes were up-regulated (ADAM2, HO-1, UCP-2, and thymosin beta4 in the early phase and clusterin, vanin1, fibronectin, heat-responsive protein 12 and FK506 binding protein in the established phase), whereas another nine were down-regulated (glutamine synthetase, cytochrome p450 IId6, and cyp 2d9 in the early phase and cyp 4a14, Xist gene, PPARgamma, alpha-albumin, uromodulin, and ADH B2 in the established phase). The identities of these 18 genes were sequence-verified. Changes in gene expression of ADAM2, cyp2d6, fibronectin, HO-1 and PPARgamma were confirmed by quantitative real-time polymerase chain reaction (PCR). ADAM2, cyp2d6, and PPARgamma have not previously been known to be involved in ARF.Using DNA microarray technology, we identified changes in expression of 18 genes during renal ischemia-reperfusion injury in the rat. We confirmed changes in five genes (fibronectin, ADAM2, cyp 2d6, HO-1 and PPARgamma) by quantitative real-time PCR. Several genes, not previously been identified as playing a role in ischemic ARF, may have importance in this disease.

  View details for Web of Science ID 000175054200009

  View details for PubMedID 11967014

• DNA microarray analysis of complex biologic processes JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kurella, M., Hsiao, L. L., Yoshida, T., Randall, J. D., Chow, G., Sarang, S. S., Jensen, R. V., Gullans, S. R. 2001; 12 (5): 1072-1078

  Abstract

  DNA microarrays, or gene chips, allow surveys of gene expression, (i.e., mRNA expression) in a highly parallel and comprehensive manner. The pattern of gene expression produced, known as the expression profile, depicts the subset of gene transcripts expressed in a cell or tissue. At its most fundamental level, the expression profile can address qualitatively which genes are expressed in disease states. However, with the aid of bioinformatics tools such as cluster analysis, self-organizing maps, and principle component analysis, more sophisticated questions can be answered. Microarrays can be used to characterize the functions of novel genes, identify genes in a biologic pathway, analyze genetic variation, and identify therapeutic drug targets. Moreover, the expression profile can be used as a tissue or disease "fingerprint." This review details the fabrication of arrays, data management tools, and applications of microarrays to the field of renal research and the future of clinical practice.

  View details for Web of Science ID 000168307600024

  View details for PubMedID 11316867

• Pharmacological and molecular mechanisms of renal cytoprotection revealed through high throughput bioassays and DNA microarrays. Gullans, S., Sarang, S., Yoshida, T., Mueller, E., Hsiao, L. L., Randall, J., Chow, G., Cadet, R., Kurella, M. FEDERATION AMER SOC EXP BIOL. 2001: A851

  View details for Web of Science ID 000167454200796

• The development of post transplant erythrocytosis in hypercalcemic renal transplant patients Kurella, M., Smith, Butterly, D. W. LIPPINCOTT WILLIAMS & WILKINS. 1999: S169

  View details for DOI 10.1097/00007890-199904150-00675

  View details for Web of Science ID 000079910700675