Bio


Dr. Montez-Rath completed her PhD in Biostatistics from Boston University in 2008 focusing on methods for modeling interaction effects in studies involving populations with high levels of comorbidity, such as persons on dialysis. She is a senior biostatistician and director of the Biostatistics Core of the Division of Nephrology at Stanford University where she has been collaborating with faculty and fellows since 2010 to study a variety of research questions relevant to kidney disease. Her methodological interests are mainly data-driven and include the handling of missing data, survival analysis with an emphasis on models for time-varying covariates and competing risks, methods for analyzing epidemiologic studies, analysis of correlated data and comparative effectiveness studies, as well as data visualization.

Current Role at Stanford


Director of the Biostatistics Core, Stanford Division of Nephrology (2016 - Present)

Honors & Awards


  • Anthony J. John Award for excellency in mathematics, University of Massachusetts, Dartmouth (1998)
  • Student Paper Award, American Statistical Association, Health Policy Statistics Section (2004)

Education & Certifications


  • Ph.D., Boston University, Biostatistics (2008)
  • M.S., University of Massachusetts, Amherst, Statistics (2001)
  • B.S., University of Massachusetts, Dartmouth, Computer oriented Mathematics (1999)

Professional Affiliations and Activities


  • Member, American Statistical Association (2005 - Present)

All Publications


  • Groundwater constituents and the incidence of kidney cancer. Cancer Soerensen, S. J., Montez-Rath, M. E., Cheng, I., Gomez, S. L., Oh, D. L., Jackson, C., Li, J., Rehkopf, D., Chertow, G. M., Langston, M. E., Ganesan, C., Pao, A. C., Chung, B. I., Leppert, J. T. 2023

    Abstract

    Kidney cancer incidence demonstrates significant geographic variation suggesting a role for environmental risk factors. This study sought to evaluate associations between groundwater exposures and kidney cancer incidence.The authors identified constituents from 18,506 public groundwater wells in all 58 California counties measured in 1996-2010, and obtained county-level kidney cancer incidence data from the California Cancer Registry for 2003-2017. The authors developed a water-wide association study (WWAS) platform using XWAS methodology. Three cohorts were created with 5 years of groundwater measurements and 5-year kidney cancer incidence data. The authors fit Poisson regression models in each cohort to estimate the association between county-level average constituent concentrations and kidney cancer, adjusting for known risk factors: sex, obesity, smoking prevalence, and socioeconomic status at the county level.Thirteen groundwater constituents met stringent WWAS criteria (a false discovery rate <0.10 in the first cohort, followed by p values <.05 in subsequent cohorts) and were associated with kidney cancer incidence. The seven constituents directly related to kidney cancer incidence (and corresponding standardized incidence ratios) were chlordane (1.06; 95% confidence interval [CI], 1.02-1.10), dieldrin (1.04; 95% CI, 1.01-1.07), 1,2-dichloropropane (1.04; 95% CI, 1.02-1.05), 2,4,5-TP (1.03; 95% CI, 1.01-1.05), glyphosate (1.02; 95% CI, 1.01-1.04), endothall (1.02; 95% CI, 1.01-1.03), and carbaryl (1.02; 95% CI, 1.01-1.03). Among the six constituents inversely related to kidney cancer incidence, the standardized incidence ratio furthest from the null was for bromide (0.97; 95% CI, 0.94-0.99).This study identified several groundwater constituents associated with kidney cancer. Public health efforts to reduce the burden of kidney cancer should consider groundwater constituents as environmental exposures that may be associated with the incidence of kidney cancer.

    View details for DOI 10.1002/cncr.34898

    View details for PubMedID 37287332

  • An Overview of Current Methods for Real-World Applications to Generalize or Transport Clinical Trial Findings to Target Populations of Interest. Epidemiology (Cambridge, Mass.) Ling, A. Y., Montez-Rath, M. E., Carita, P., Chandross, K. J., Lucats, L., Meng, Z., Sebastien, B., Kapphahn, K., Desai, M. 2023

    Abstract

    It has been well established that randomized clinical trials have poor external validity, resulting in findings that may not apply to relevant - or target - populations. When the trial is sampled from the target population, generalizability methods have been proposed to address the applicability of trial findings to target populations. When the trial sample and target populations are distinct, transportability methods may be applied for this purpose. However, generalizability and transportability studies present challenges, particularly around the strength of their conclusions. We review and summarize state-of-the-art methods for translating trial findings to target populations. We additionally provide a novel step-by-step guide to address these challenges, illustrating principles through a published case study. When conducted with rigor, generalizability and transportability studies can play an integral role in regulatory decisions by providing key real-world evidence.

    View details for DOI 10.1097/EDE.0000000000001633

    View details for PubMedID 37255252

  • 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

  • SARS-CoV-2 Infection during the Omicron Surge among Patients Receiving Dialysis: The Role of Circulating Receptor-Binding Domain Antibodies and Vaccine Doses. Journal of the American Society of Nephrology : JASN Montez-Rath, M. E., Garcia, P., Han, J., Cadden, L., Hunsader, P., Morgan, C., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Parsonnet, J., Chertow, G. M., Anand, S. 2022

    Abstract

    It is unclear whether circulating antibody levels conferred protection against SARS-CoV-2 infection among patients receiving dialysis during the Omicron-dominant period.We followed monthly semiquantitative SARS-CoV-2 RBD IgG index values in a randomly selected nationwide cohort of patients receiving dialysis and ascertained SARS-CoV-2 infection during the Omicron-dominant period of December 25, 2021 to January 31, 2022 using electronic health records. We estimated the relative risk for documented SARS-CoV-2 infection by vaccination status and by circulating RBD IgG using a log-binomial model accounting for age, sex, and prior COVID-19.Among 3576 patients receiving dialysis, 901 (25%) received a third mRNA vaccine dose as of December 24, 2021. Early antibody responses to third doses were robust (median peak index IgG value at assay limit of 150). During the Omicron-dominant period, SARS-CoV-2 infection was documented in 340 (7%) patients. Risk for infection was higher among patients without vaccination and with one to two doses (RR, 2.1; 95% CI, 1.6 to 2.8, and RR, 1.3; 95% CI, 1.0 to 1.8 versus three doses, respectively). Irrespective of the number of vaccine doses, risk for infection was higher among patients with circulating RBD IgG <23 (506 BAU/ml) (RR range, 2.1 to 3.2, 95% CI, 1.3 to 3.4 and 95% CI, 2.2 to 4.5, respectively) compared with RBD IgG ≥23.Among patients receiving dialysis, a third mRNA vaccine dose enhanced protection against SARS-CoV-2 infection during the Omicron-dominant period, but a low circulating RBD antibody response was associated with risk for infection independent of the number of vaccine doses. Measuring circulating antibody levels in this high-risk group could inform optimal timing of vaccination and other measures to reduce risk of SARS-CoV-2 infection.

    View details for DOI 10.1681/ASN.2022040504

    View details for PubMedID 35973733

  • Characterizing real world safety profile of oral Janus kinase inhibitors among adult atopic dermatitis patients: evidence transporting from the rheumatoid arthritis population. Current medical research and opinion Montez-Rath, M. E., Lubwama, R., Kapphahn, K., Ling, A. Y., LoCasale, R., Robinson, L., Chandross, K. J., Desai, M. 2022: 1-33

    Abstract

    OBJECTIVE: To address potential safety concerns of Janus Kinase Inhibitors (JAK-Is), we characterized their safety profile in the atopic dermatitis (AD) patient population.METHODS: In this retrospective observational study, we used propensity score-based methods and a Poisson modeling framework to estimate the incidence of health outcomes of interest (HOI) for the AD patient. To that end, two mutually exclusive cohorts were created using a real world data resource: a rheumatoid arthritis (RA) cohort, where we directly quantify the safety risk of JAK-Is on HOIs, and an AD cohort, that comprises the target population of interest and to whom we transport the results obtained from the RA cohort. The RA cohort included all adults who filled at least one prescription for a JAK-I (tofacitinib, baricitinib, or upadacitinib) between January 1, 2017 and January 31, 2020. The AD cohort consisted of all adults diagnosed with AD during the same period. We first estimated the incidence rate of each HOI in the RA cohort, and then transported the results to the AD population.RESULTS: The RA and AD cohorts included 5,296 and 261,855 patients, respectively. On average, patients in the AD cohort were younger, more often male, more likely to be Asian, and had higher household income. They also had a lower prevalence of several comorbid conditions including hypertension, chronic kidney disease, obesity, and depression. Overall, the transported incidence rates of the HOIs to the AD cohort were lower than those obtained in the RA cohort by 13%-50%.CONCLUSION: We applied transportability methods to characterize the risk of the HOIs in the AD population and found absolute risks higher than that of the general population. Future work is needed to validate these conclusions in comparable populations.

    View details for DOI 10.1080/03007995.2022.2088715

    View details for PubMedID 35699028

  • SARS-CoV-2 infection during the Omicron surge among patients receiving dialysis: the role of circulating receptor-binding domain antibodies and vaccine doses. medRxiv : the preprint server for health sciences Montez-Rath, M. E., Garcia, P., Han, J., Cadden, L., Hunsader, P., Morgan, C., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Anand, S., Parsonnet, J., Chertow, G. M. 2022

    Abstract

    Background: It is unclear whether a third dose of mRNA platform vaccines, or antibody response to prior infection or vaccination confer protection from the Omicron variant among patients receiving dialysis.Methods: Monthly since February 2021, we tested plasma from 4,697 patients receiving dialysis for antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. We assessed semiquantitative median IgG index values over time among patients vaccinated with at least one dose of the two mRNA vaccines. We ascertained documented COVID-19 diagnoses after December 25, 2021 and up to January 31, 2022. We estimated the relative risk for documented SARS-CoV-2 infection by vaccination status using a log-binomial model accounting for age, sex, and prior clinical COVID-19. Among patients with RBD IgG index value available during December 1-December 24, 2021, we also evaluated the association between the circulating RBD IgG titer and risk for Omicron variant SARS-CoV-2 infection.Results: Of the 4,697 patients we followed with monthly RBD assays, 3576 are included in the main analysis cohort; among these, 852 (24%) were unvaccinated. Antibody response to third doses was robust (median peak index IgG value at assay limit of 150, equivalent to 3270 binding antibody units/mL). Between December 25-January 31, 2022, SARS-CoV-2 infection was documented 340 patients (7%), 115 (36%) of whom were hospitalized. The final doses of vaccines were given a median of 272 (25 th , 75 th percentile, 245-303) days and 58 (25 th , 75 th percentile, 51-95) days prior to infection for the 1-2 dose and 3 dose vaccine groups respectively. Relative risks for infection were higher among patients without vaccination (RR 2.1 [95%CI 1.6, 2.8]), and patients with 1-2 doses (RR 1.3 [95%CI 1.0, 1.8]), compared with patients with three doses of the mRNA vaccines. Relative risks for infection were higher among patients with RBD index values < 23 (506 BAU/mL), compared with RBD index value a 23 (RR 2.4 [95%CI 1.9, 3.0]). The higher risk for infection among patients with RBD index values < 23 was present among patients who received three doses (RR 2.1 [95%CI 1.3, 3.4]).Conclusions: Among patients receiving hemodialysis, patients unvaccinated, without a third mRNA vaccine dose, or those lacking robust circulating antibody response are at higher risk for Omicron variant infection. Low circulating antibodies could identify the subgroup needing intensified surveillance, prophylaxis or treatment in this patient population.

    View details for DOI 10.1101/2022.03.15.22272426

    View details for PubMedID 35313586

  • COVID19 Vaccine Type and Humoral Immune Response in Patients Receiving Dialysis. Journal of the American Society of Nephrology : JASN Garcia, P., Anand, S., Han, J., Montez-Rath, M., Sun, S., Shang, T., Parsonnet, J., Chertow, G., Schiller, B., Abra, G. 2021

    View details for DOI 10.1681/ASN.2021070936

    View details for PubMedID 34645698

  • Serial SARS-CoV-2 Receptor-Binding Domain Antibody Responses in Patients Receiving Dialysis. Annals of internal medicine Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Cadden, L., Hunsader, P., Kerschmann, R., Beyer, P., Boyd, S. D., Chertow, G. M., Parsonnet, J. 2021

    Abstract

    BACKGROUND: Assessing the evolution of SARS-CoV-2 immune response among patients receiving dialysis can define its durability in a highly clinically relevant context because patients receiving dialysis share the characteristics of persons most susceptible to SARS-CoV-2 infection.OBJECTIVE: To evaluate the persistence of SARS-CoV-2 receptor-binding domain (RBD) IgG in seroprevalent patients receiving dialysis.DESIGN: Prospective.SETTING: Nationwide sample from dialysis facilities.PATIENTS: 2215 patients receiving dialysis who had evidence of SARS-CoV-2 infection as of July 2020.MEASUREMENTS: Remainder plasma from routine monthly laboratories was used to measure semiquantitative RBD IgG index value over 6 months.RESULTS: A total of 2063 (93%) seroprevalent patients reached an assay detectable response (IgG index value ≥1). Most (n = 1323, 60%) had responses in July with index values classified as high (IgG ≥10); 1003 (76%) remained within this stratum. Adjusted median index values declined slowly but continuously (July vs. December values were 21 vs. 13; P < 0.001). The trajectory of the response did not vary by age group, sex, race/ethnicity, or diabetes status. Patients without an assay detectable response (n = 137) were more likely to be White and in the younger (18 to 44 years) or older (≥80 years) age groups and less likely to have diabetes and hypoalbuminemia.LIMITATION: Lack of data on symptoms or reverse transcriptase polymerase chain reaction diagnosis, cohort of persons who survived infection, and use of a semiquantitative assay.CONCLUSION: Despite impaired immunity, most seropositive patients receiving dialysis maintained RBD antibody levels over 6 months. A slow and continual decline in median antibody levels over time was seen, but no indication that subgroups with impaired immunity had a shorter-lived humoral response was found.PRIMARY FUNDING SOURCE: Ascend Clinical Laboratories.

    View details for DOI 10.7326/M21-0256

    View details for PubMedID 34000201

  • 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

  • SARS-CoV-2 Vaccine Acceptability in Patients on Hemodialysis: A Nationwide Survey. Journal of the American Society of Nephrology : JASN Garcia, P., Montez-Rath, M. E., Moore, H., Flotte, J., Fults, C., Block, M. S., Han, J., Dittrich, M., Parsonnet, J., Chertow, G. M., Block, G. A., Anand, S. 2021

    Abstract

    BACKGROUND: Patients on dialysis are at increased risk for COVID-19-related complications. However, a substantial fraction of patients on dialysis belong to groups more likely to be hesitant about vaccination.METHODS: With the goal of identifying strategies to increase COVID-19 vaccine uptake among patients on hemodialysis, we conducted a nationwide vaccine acceptability survey, partnering with a dialysis network to distribute an anonymized English and Spanish language online survey in 150 randomly selected facilities in the United States. We used logistic regression to evaluate characteristics of vaccine-hesitant persons.RESULTS: A total of 1515 (14% of eligible) patients responded; 20% of all responders, 29% of patients aged 18-44 years, and 29% of Black responders reported being hesitant to seek the COVID-19 vaccine, even if the vaccine was considered safe for the general population. Odds of vaccine hesitancy were higher among patients aged 18-44 years versus those 45-64 years (odds ratio [OR], 1.5; 95% confidence interval [95% CI], 1.0 to 2.3), Black patients versus non-Hispanic White patients (OR, 1.9; 95% CI, 1.3 to 2.7), Native Americans or Pacific Islanders versus non-Hispanic White patients (OR, 2.0; 95% CI, 1.1 to 3.7), and women versus men (OR, 1.6; 95% CI, 1.2 to 2.0). About half (53%) of patients who were vaccine hesitant expressed concerns about side effects. Responders' main information sources about COVID-19 vaccines were television news and dialysis staff (68% and 38%, respectively).CONCLUSIONS: A substantial proportion of patients receiving in-center hemodialysis in the United States are hesitant about seeking COVID-19 vaccination. Facilitating uptake requires outreach to younger patients, women, and Black, Native American, or Pacific Islander patients, and addressing concerns about side effects.

    View details for DOI 10.1681/ASN.2021010104

    View details for PubMedID 33927004

  • Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA: a cross-sectional study. Lancet (London, England) Anand, S. n., Montez-Rath, M. n., Han, J. n., Bozeman, J. n., Kerschmann, R. n., Beyer, P. n., Parsonnet, J. n., Chertow, G. M. 2020

    Abstract

    Many patients receiving dialysis in the USA share the socioeconomic characteristics of underserved communities, and undergo routine monthly laboratory testing, facilitating a practical, unbiased, and repeatable assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence.For this cross-sectional study, in partnership with a central laboratory that receives samples from approximately 1300 dialysis facilities across the USA, we tested the remainder plasma of 28 503 randomly selected adult patients receiving dialysis in July, 2020, using a spike protein receptor binding domain total antibody chemiluminescence assay (100% sensitivity, 99·8% specificity). We extracted data on age, sex, race and ethnicity, and residence and facility ZIP codes from the anonymised electronic health records, linking patient-level residence data with cumulative and daily cases and deaths per 100 000 population and with nasal swab test positivity rates. We standardised prevalence estimates according to the overall US dialysis and adult population, and present estimates for four prespecified strata (age, sex, region, and race and ethnicity).The sampled population had similar age, sex, and race and ethnicity distribution to the US dialysis population, with a higher proportion of older people, men, and people living in majority Black and Hispanic neighbourhoods than in the US adult population. Seroprevalence of SARS-CoV-2 was 8·0% (95% CI 7·7-8·4) in the sample, 8·3% (8·0-8·6) when standardised to the US dialysis population, and 9·3% (8·8-9·9) when standardised to the US adult population. When standardised to the US dialysis population, seroprevalence ranged from 3·5% (3·1-3·9) in the west to 27·2% (25·9-28·5) in the northeast. Comparing seroprevalent and case counts per 100 000 population, we found that 9·2% (8·7-9·8) of seropositive patients were diagnosed. When compared with other measures of SARS-CoV-2 spread, seroprevalence correlated best with deaths per 100 000 population (Spearman's ρ=0·77). Residents of non-Hispanic Black and Hispanic neighbourhoods experienced higher odds of seropositivity (odds ratio 3·9 [95% CI 3·4-4·6] and 2·3 [1·9-2·6], respectively) compared with residents of predominantly non-Hispanic white neighbourhoods. Residents of neighbourhoods in the highest population density quintile experienced increased odds of seropositivity (10·3 [8·7-12·2]) compared with residents of the lowest density quintile. County mobility restrictions that reduced workplace visits by at least 5% in early March, 2020, were associated with lower odds of seropositivity in July, 2020 (0·4 [0·3-0·5]) when compared with a reduction of less than 5%.During the first wave of the COVID-19 pandemic, fewer than 10% of the US adult population formed antibodies against SARS-CoV-2, and fewer than 10% of those with antibodies were diagnosed. Public health efforts to limit SARS-CoV-2 spread need to especially target racial and ethnic minority and densely populated communities.Ascend Clinical Laboratories.

    View details for DOI 10.1016/S0140-6736(20)32009-2

    View details for PubMedID 32987007

  • Using GIS Mapping to Track Hot Spots of Kidney Disease in California. The New England journal of medicine Anand, S. n., Staniec, A. n., Montez-Rath, M. n., Vlahos, P. n. 2020; 382 (23): 2265–67

    View details for DOI 10.1056/NEJMc2001023

    View details for PubMedID 32492310

  • Prospective Biopsy-Based Study of Chronic Kidney Disease of Unknown Etiology in Sri Lanka. Clinical journal of the American Society of Nephrology : CJASN Anand, S., Montez-Rath, M. E., Adasooriya, D., Ratnatunga, N., Kambham, N., Wazil, A., Wijetunge, S., Badurdeen, Z., Ratnayake, C., Karunasena, N., Schensul, S. L., Valhos, P., Haider, L., Bhalla, V., Levin, A., Wise, P. H., Chertow, G. M., Barry, M., Fire, A. Z., Nanayakkara, N. 2019

    Abstract

    BACKGROUND AND OBJECTIVES: A kidney disease of unknown cause is common in Sri Lanka's lowland (dry) region. Detailed clinical characterizations of patients with biopsy-proven disease are limited, and there is no current consensus on criteria for a noninvasive diagnosis.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We designed a prospective study in a major Sri Lankan hospital servicing endemic areas to ascertain pathologic and clinical characteristics of and assess risk factors for primary tubulointerstitial kidney disease. We used logistic regression to determine whether common clinical characteristics could be used to predict the presence of primary tubulointerstitial kidney disease on kidney biopsy.RESULTS: From 600 new patients presenting to a tertiary nephrology clinic over the course of 1 year, 87 underwent kidney biopsy, and 43 (49%) had a biopsy diagnosis of primary tubulointerstitial kidney disease. On detailed biopsy review, 13 (30%) had evidence of moderate to severe active kidney disease, and six (15%) had evidence of moderate to severe chronic tubulointerstitial kidney disease. Patients with tubulointerstitial kidney disease were exclusively born in endemic provinces; 91% spent a majority of their lifespan there. They were more likely men and farmers (risk ratio, 2.0; 95% confidence interval, 1.2 to 2.9), and they were more likely to have used tobacco (risk ratio, 1.7; 95% confidence interval, 1.0 to 2.3) and well water (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). Three clinical characteristics-age, urine dipstick for protein, and serum albumin-could predict likelihood of tubulointerstitial kidney disease on biopsy (model sensitivity of 79% and specificity of 84%). Patients referred for kidney biopsy despite comorbid diabetes or hypertension did not experience lower odds of tubulointerstitial kidney disease.CONCLUSIONS: A primary tubulointerstitial kidney disease occurs commonly in specific regions of Sri Lanka with characteristic environmental and lifestyle exposures.PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_01_18_CJASNPodcast_19_02_.mp3.

    View details for PubMedID 30659059

  • Missing data strategies for time-varying confounders in comparative effectiveness studies of non-missing time-varying exposures and right-censored outcomes. Statistics in medicine Desai, M. n., Montez-Rath, M. E., Kapphahn, K. n., Joyce, V. R., Mathur, M. B., Garcia, A. n., Purington, N. n., Owens, D. K. 2019

    Abstract

    The treatment of missing data in comparative effectiveness studies with right-censored outcomes and time-varying covariates is challenging because of the multilevel structure of the data. In particular, the performance of an accessible method like multiple imputation (MI) under an imputation model that ignores the multilevel structure is unknown and has not been compared to complete-case (CC) and single imputation methods that are most commonly applied in this context. Through an extensive simulation study, we compared statistical properties among CC analysis, last value carried forward, mean imputation, the use of missing indicators, and MI-based approaches with and without auxiliary variables under an extended Cox model when the interest lies in characterizing relationships between non-missing time-varying exposures and right-censored outcomes. MI demonstrated favorable properties under a moderate missing-at-random condition (absolute bias <0.1) and outperformed CC and single imputation methods, even when the MI method did not account for correlated observations in the imputation model. The performance of MI decreased with increasing complexity such as when the missing data mechanism involved the exposure of interest, but was still preferred over other methods considered and performed well in the presence of strong auxiliary variables. We recommend considering MI that ignores the multilevel structure in the imputation model when data are missing in a time-varying confounder, incorporating variables associated with missingness in the MI models as well as conducting sensitivity analyses across plausible assumptions.

    View details for DOI 10.1002/sim.8174

    View details for PubMedID 31099433

  • 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

  • Guidelines for Generating Right-Censored Outcomes from a Cox Model Extended to Accommodate Time-Varying Covariates JOURNAL OF MODERN APPLIED STATISTICAL METHODS Montez-Rath, M. E., Kapphahn, K., Mathur, M. B., Mitani, A. A., Hendry, D. J., Desai, M. 2017; 16 (1): 86–106
  • Addressing Missing Data in Clinical Studies of Kidney Diseases CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Montez-Rath, M. E., Winkelmayer, W. C., Desai, M. 2014; 9 (7): 1328-1335

    Abstract

    Missing data constitute a problem present in all studies of medical research. The most common approach to handling missing data-complete case analysis-relies on assumptions about missing data that rarely hold in practice. The implications of this approach are biased and inefficient descriptions of relationships of interest. Here, various approaches for handling missing data in clinical studies are described. In particular, this work promotes the use of multiple imputation methods that rely on assumptions about missingness that are more flexible than those assumptions relied on by the most common method in use. Furthermore, multiple imputation methods are becoming increasingly more accessible in mainstream statistical software packages, making them both a sound and practical choice. The use of multiple imputation methods is illustrated with examples pertinent to kidney research, and concrete guidance on their use is provided.

    View details for DOI 10.2215/CJN.10141013

    View details for Web of Science ID 000338615300024

  • Clinical Outcomes after a Kidney Stone Event in Kidney Transplant Recipients. Clinical journal of the American Society of Nephrology : CJASN Ganesan, C., Liu, S., Montez-Rath, M., Leppert, J. T., Pao, A. C. 2024

    View details for DOI 10.2215/CJN.0000000000000451

    View details for PubMedID 38480494

  • Defining systolic blood pressure normative values in hospitalized pediatric patients: a single center experience. Pediatric research Uber, A. M., Han, J., Grimm, P., Montez-Rath, M. E., Chaudhuri, A. 2024

    Abstract

    Normative blood pressure (BP) values and definition of hypertension (HTN) in children in outpatient setting cannot be reliably used for inpatient therapy initiation. No normative exists to describe HTN in hospitalized pediatric populations. We aimed to study the prevalence of hypertension and produce normative BP values in hospitalized children.Cross sectional observational study of all children hospitalized on acute care floors, ≥2 and <18 years age, at Stanford Children's Hospital, from Jan-01-2014 to Dec-31-2018. Cohort included 7468 hospital encounters with a total of 118,423 automated, oscillometric, BPs measured in the upper extremity during a hospitalization of >24 hours.Overall prevalence of HTN, defined by outpatient guidelines, was 12-48% in boys and 6-39% in girls, stage 1 systolic HTN in 12-38% of boys and 6-31% of girls, stage 2 systolic HTN in 3-10% of boys and 1-8% of girls. Centile curves were derived demonstrating overall higher BP reading for hospitalized patients compared to the outpatient setting.Higher blood pressures are anticipated during hospitalization. Thresholds provided by the centile curves generated in this study may provide the clinician with some guidance on how to manage hospitalized pediatric patients based on clinical circumstances.Hospitalized children have higher blood pressures compared to patients in the ambulatory setting, hence outpatient normative blood pressure values cannot be reliably used for inpatient therapy initiation. No normative exists to describe hypertension in hospitalized pediatric populations. The thresholds provided by the centile curves generated in this study may provide the clinician with some guidance on how to manage hospitalized pediatric patients based on clinical circumstances.

    View details for DOI 10.1038/s41390-024-03059-w

    View details for PubMedID 38326477

    View details for PubMedCentralID 6784751

  • Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Active Kidney Involvement in the United States: 2016-2020. Glomerular diseases Tao, J., Liu, S., Montez-Rath, M., Charu, V., Chertow, G. M. 2024; 4 (1): 33-42

    Abstract

    Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its subtypes, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA), frequently present with acute kidney injury and can often lead to kidney failure, even with successful induction therapy. Few contemporary, nationally representative studies have described hospital complications of AAV.Using data from the 2016-2020 National Inpatient Sample, a nationally representative database, we identified hospitalizations from adults with a new diagnosis of AAV (subtype or unspecified) and an inpatient kidney biopsy during the index hospitalization. We described baseline characteristics, associated inpatient procedures and complications, and compared lengths of stay and costs by geographic region, hospital characteristics, and AAV subtype.We identified an average of 1,329 cases of hospitalized AAV with a concurrent kidney biopsy per year over the 5-year period. More than 50% were not designated as having a specific subtype, likely owing to delays in documentation of histopathology. Kidney involvement was severe as the majority of patients developed acute kidney injury, and the proportion of patients who required inpatient dialysis was approximately 24%. Approximately 20% of patients developed hypoxia. Inpatient plasmapheresis was delivered to 20.4% and 20.6% of patients with GPA and MPA, respectively. There were no clinically meaningful or statistically significant differences in adjusted length of stay or inpatient costs among AAV subtypes. Admission in the Midwest region was associated with shorter hospital stays and lower costs than that in the Northeast, South, or West regions of the USA (adjusted p = 0.007 and <0.001, respectively).AAV with acute kidney involvement remains a challenging, high-risk condition. Maintaining a high index of suspicion and a low threshold for kidney biopsy should help ameliorate short- and long-term complications.

    View details for DOI 10.1159/000536168

    View details for PubMedID 38328771

    View details for PubMedCentralID PMC10849749

  • Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes and mild/moderate chronic kidney disease. Diabetes, obesity & metabolism Rhee, J. J., Han, J., Montez-Rath, M. E., Chertow, G. M. 2024

    Abstract

    To determine the comparative effectiveness regarding major cardiovascular events of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).We assembled a cohort of commercially insured adult patients with T2DM in the United States (derived from Optum Clinformatics DataMart 2003-2021) who were new users of GLP-1 receptor agonists or SGLT-2 inhibitors. We compared risks of non-fatal myocardial infarction or stroke in patients with and without CKD, and further categorized by CKD stage: stages G1 or G2 [estimated glomerular filtration rate (eGFR) ≥60 ml/min] and A2 (urine albumin to creatinine ratio 30 to <300 mg/g) or A3 (urine albumin to creatinine ratio ≥300 mg/g), stage G3a (eGFR 45 to <60 ml/min/1.73 m2 ) and stage G3b (eGFR 30 to <45 ml/min/1.73 m2 ). We used proportional hazards regression after inverse probability of treatment weighting to compute hazard ratios and 95% confidence intervals.After accounting for the probability of treatment, patients with T2DM and CKD treated with SGLT-2 inhibitors experienced a 14% lower risk of non-fatal myocardial infarction or stroke (hazard ratio 0.86, 95% confidence interval 0.78-0.94) relative to those treated with GLP-1 receptor agonists.Recognizing the potential for residual confounding, selection bias and immortal time bias, commercially insured patients in the United States with T2DM and CKD treated with SGLT-2 inhibitors experienced significantly lower risks of non-fatal myocardial infarction or stroke relative to those treated with GLP-1 receptor agonists.

    View details for DOI 10.1111/dom.15427

    View details for PubMedID 38186297

  • Dialysis Modality, Transplant Characteristics, and Incident Atrial Fibrillation After Kidney Transplant: An Observational Study Using USRDS Data. Kidney medicine Garcia, L. P., Liu, S., Lenihan, C. R., Montez-Rath, M. E., Chang, T. I., Winkelmayer, W. C., Khairallah, P. 2024; 6 (1): 100741

    Abstract

    Atrial fibrillation is the most common arrhythmia and is increasing in prevalence. The prevalence of atrial fibrillation is high among patients receiving dialysis, affecting ∼21.3% of the patients receiving hemodialysis and 15.5% of those receiving peritoneal dialysis. The association of previous dialysis modality with incident atrial fibrillation in patients after receiving their first kidney transplant has not been studied.We used the United States Renal Data System to retrospectively identify adult, Medicare-insured patients who received their first kidney transplant between January 1, 2005, and September 30, 2012 and who had not previously been diagnosed with atrial fibrillation.The study included 43,621 patients who were aged 18 years older when receiving a first kidney transplant between January 1, 2005, and September 30, 2012 and whose primary payer was Medicare (parts A and B) at the time of transplantation and the 6 months preceding it.Dialysis modality used before transplant.Time to incidence of atrial fibrillation up to 3 years posttransplant.Multivariable Cox regression was used to estimate HRs.Of 43,621 patients, 84.9% received hemodialysis and 15.1% received peritoneal dialysis before transplant. The mean ± SD age was 51 ± 13.6 years; 60.8% were male, 55.6% White, and 35.8% Black race. The mean dialysis vintage was 4.3 ± 2.8 years. Newly diagnosed atrial fibrillation after kidney transplant occurred in 286 patients (during 15,363 person-years) who had received peritoneal dialysis and in 2,315 patients (during 83,536 person-years) who had received hemodialysis. After multivariable adjustment, atrial fibrillation was 20% (95% CI, 4%-38%) more likely in those who had been receiving hemodialysis versus peritoneal dialysis, regardless of whether death was considered a competing risk or a censoring event. Each year of pretransplant dialysis vintage increased the risk of posttransplant atrial fibrillation by 6% (95% CI, 3%-9%).Residual confounding; data from billing claims does not specify the duration of atrial fibrillation or whether it is valvular.Pretransplant hemodialysis, as compared with peritoneal dialysis, was associated with higher risk of newly diagnosed atrial fibrillation after a first kidney transplant.New-onset atrial fibrillation (AF) occurs in 7% of kidney transplant recipients in the first 3 years posttransplantation. We conducted this study to determine whether pretransplant dialysis modality was associated with posttransplant AF. We identified 43,621 patients; 84.9% used hemodialysis and 15.1% used peritoneal dialysis pretransplant. Multivariable Cox regression was used to estimate hazard ratios. We found that patients receiving hemodialysis pretransplant were at 20% increased risk of developing posttransplant AF as compared with patients receiving peritoneal dialysis. As our understanding of transplant-specific risk factors for AF increases, we may be able to better risk-stratify transplant patients and develop monitoring and management strategies that can improve outcomes.

    View details for DOI 10.1016/j.xkme.2023.100741

    View details for PubMedID 38188456

    View details for PubMedCentralID PMC10770630

  • 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

  • Predicting transfer to haemodialysis using the peritoneal dialysis surprise question. Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis Anwaar, A., Liu, S., Montez-Rath, M., Neilsen, H., Sun, S., Abra, G., Schiller, B., Hussein, W. F. 2023: 8968608231214143

    Abstract

    People on peritoneal dialysis (PD) at risk of transfer to haemodialysis (HD) need support to remain on PD or ensure a safe transition to HD. Simple point-of-care risk stratification tools are needed to direct limited dialysis centre resources. In this study, we evaluated the utility of collecting clinicians' identification of patients at high risk of transfer to HD using a single point of care question.In this prospective observational study, we included 1275 patients undergoing PD in 35 home dialysis programmes. We modified the palliative care 'surprise question' (SQ) by asking the registered nurse and treating nephrologist: 'Would you be surprised if this patient transferred to HD in the next six months?' A 'yes' or 'no' answer indicated low and high risk, respectively. We subsequently followed patient outcomes for 6 months. Cox regression model estimated the hazard ratio (HR) of transfer to HD.Patients' mean age was 59 ± 16 years, 41% were female and the median PD vintage was 20 months (interquartile range: 9-40). Responses were received from nurses for 1123 patients, indicating 169 (15%) as high risk and 954 (85%) as low risk. Over the next 6 months, transfer to HD occurred in 18 (11%) versus 29 (3%) of the high and low-risk groups, respectively (HR: 3.92, 95% confidence interval (CI): 2.17-7.05). Nephrologist responses were obtained for 692 patients, with 118 (17%) and 574 (83%) identified as high and low risk, respectively. Transfer to HD was observed in 14 (12%) of the high-risk group and 14 (2%) of the low-risk group (HR: 5.56, 95% CI: 2.65-11.67). Patients in the high-risk group experienced higher rates of death and hospitalisation than low-risk patients, with peritonitis events being similar between the two groups.The PDSQ is a simple point of care tool that can help identify patients at high risk of transfer to HD and other poor clinical outcomes.

    View details for DOI 10.1177/08968608231214143

    View details for PubMedID 38017608

  • Building a strong collaborative biostatistics workforce: Strategies for effective intra-unit professional development activities JOURNAL OF CLINICAL AND TRANSLATIONAL SCIENCE Taylor, S. L., Podolsky, R. H., Montez-Rath, M. E., Slade, E. 2023; 7 (1)
  • Building a strong collaborative biostatistics workforce: Strategies for effective intra-unit professional development activities. Journal of clinical and translational science Taylor, S. L., Podolsky, R. H., Montez-Rath, M. E., Slade, E. 2023; 7 (1): e230

    Abstract

    Ongoing professional development is important for collaborative biostatisticians, as it enables them to remain current with the latest advances in statistical methodology and software, refine their analytical skills, and expand their domain knowledge, thereby facilitating their ability to contribute effectively to biomedical research. Although external opportunities for professional development, such as attending conferences and workshops, are widely recognized and valued in the field of biostatistics, there has been comparatively little attention given to internal opportunities for enhancing the skills and knowledge of biostatisticians which can be implemented with lower financial and time investment than external offerings. The purpose of this paper is to offer guidance for ongoing internal professional development activities that can be employed by collaborative biostatistics units in universities and academic medical centers to complement structured curricula and initial training. Specific examples of activities are provided so that collaborative biostatisticians and/or managers of biostatistical units can flexibly combine components to create an appropriately scaled, customized program that meets the needs of themselves or of the unit.

    View details for DOI 10.1017/cts.2023.653

    View details for PubMedID 38028352

    View details for PubMedCentralID PMC10643907

  • 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

  • Hypocitraturia and Risk of Bone Disease in Patients With Kidney Stone Disease. JBMR plus Ganesan, C., Thomas, I. C., Montez-Rath, M. E., Chertow, G. M., Leppert, J. T., Pao, A. C. 2023; 7 (9): e10786

    Abstract

    Patients with kidney stone disease are at higher risk for bone disease. Hypocitraturia is common in patients with kidney stone disease and a key risk factor for stone recurrence. In this retrospective cohort study, we sought to determine whether hypocitraturia is also a risk factor for incident bone disease in patients with kidney stone disease. We used nationwide data from the Veterans Health Administration and identified 9025 patients with kidney stone disease who had a 24-hour urine citrate measurement between 2007 and 2015. We examined clinical characteristics of patients by level of 24-hour urine citrate excretion (<200, 200-400, and >400 mg/d) and the time to osteoporosis or fracture according to 24-hour urine citrate excretion level. Almost one in five veterans with kidney stone disease and a 24-hour urine citrate measurement had severe hypocitraturia, defined as <200 mg/d. Patients with severe hypocitraturia were at risk for osteoporosis or fracture (hazard ratio [HR] = 1.23; confidence interval [CI] 1.03-1.48), but after adjustment for demographic factors, comorbid conditions, and laboratory abnormalities associated with hypocitraturia, the association was no longer statistically significant (HR = 1.18; CI 0.98-1.43). Our results in a predominantly male cohort suggest a modest association between hypocitraturia and osteoporosis or fracture; there are likely to be other explanations for the potent association between kidney stone disease and diminished bone health. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

    View details for DOI 10.1002/jbm4.10786

    View details for PubMedID 37701146

    View details for PubMedCentralID PMC10494504

  • Use of Wastewater Metrics to Track COVID-19 in the US. JAMA network open Varkila, M. R., Montez-Rath, M. E., Salomon, J. A., Yu, X., Block, G. A., Owens, D. K., Chertow, G. M., Parsonnet, J., Anand, S. 2023; 6 (7): e2325591

    Abstract

    Importance: Widespread use of at-home COVID-19 tests hampers determination of community COVID-19 incidence.Objective: To examine the association of county-level wastewater metrics with high case and hospitalization rates nationwide both before and after widespread use of at-home tests.Design, Setting, and Participants: This observational cohort study with a time series analysis was conducted from January to September 2022 in 268 US counties in 22 states participating in the US Centers for Disease Control and Prevention's National Wastewater Surveillance System. Participants included the populations of those US counties.Exposures: County level of circulating SARS-CoV-2 as determined by metrics based on viral wastewater concentration relative to the county maximum (ie, wastewater percentile) and 15-day percentage change in SARS-CoV-2 (ie, percentage change).Main Outcomes and Measures: High county incidence of COVID-19 as evidenced by dichotomized reported cases (current cases ≥200 per 100 000 population) and hospitalization (≥10 per 100 000 population lagged by 2 weeks) rates, stratified by calendar quarter.Results: In the first quarter of 2022, use of the wastewater percentile detected high reported case (area under the curve [AUC], 0.95; 95% CI, 0.94-0.96) and hospitalization (AUC, 0.86; 95% CI, 0.84-0.88) rates. The percentage change metric performed poorly, with AUCs ranging from 0.51 (95% CI, 0.50-0.53) to 0.57 (95% CI, 0.55-0.59) for reported new cases, and from 0.50 (95% CI, 0.48-0.52) to 0.55 (95% CI, 0.53-0.57) for hospitalizations across the first 3 quarters of 2022. The Youden index for detecting high case rates was wastewater percentile of 51% (sensitivity, 0.82; 95% CI, 0.80-0.84; specificity, 0.93; 95% CI, 0.92-0.95). A model inclusive of both metrics performed no better than using wastewater percentile alone. The performance of wastewater percentile declined over time for cases in the second quarter (AUC, 0.84; 95% CI, 0.82-0.86) and third quarter (AUC, 0.72; 95% CI, 0.70-0.75) of 2022.Conclusions and Relevance: In this study, nationwide, county wastewater levels relative to the county maximum were associated with high COVID-19 case and hospitalization rates in the first quarter of 2022, but there was increasing dissociation between wastewater and clinical metrics in subsequent quarters, which may reflect increasing underreporting of cases, reduced testing, and possibly lower virulence of infection due to vaccines and treatments. This study offers a strategy to operationalize county wastewater percentile to improve the accurate assessment of community SARS-CoV-2 infection prevalence when reliability of conventional surveillance data is declining.

    View details for DOI 10.1001/jamanetworkopen.2023.25591

    View details for PubMedID 37494040

  • Describing Natural History and Exploring Risk Factors for Kidney Function Decline in Persons With CKD of Uncertain Etiology in Sri Lanka. Kidney international reports Hewavitharana, P., Schensul, S., Lee, E., Montez-Rath, M., Senarathne, S., Liu, S., Harold, K., Hewapathiranage, S., Erandika, N., Abeysundara, H. T., Yu, X., Bhalla, V., Fire, A., Levin, A., Anand, S., Vlahos, P., Chandrajith, R., Nanayakkara, N. 2023; 8 (7): 1430-1438

    Abstract

    Chronic kidney disease of uncertain etiology (CKDu) is a leading cause of death of adults in Sri Lanka's dry region.We initiated the Kidney Progression Project (KiPP) to prospectively follow 292 persons with Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) 20 to 60 ml/min per 1.73 m2 living in a CKDu endemic area. Using data from 3-year follow-up, we assessed kidney function decline (>30% from baseline eGFR), and the composite outcome of >30% eGFR decline, eGFR <15 ml/min or death, and explored the association of the 2 outcomes with baseline demographic, residential, and clinical parameters accounting for baseline eGFR.Median eGFR at enrollment was 28 ml/min among 71 women; 30 ml/min among 221 men; 91% to 99% had trace or no proteinuria during follow-up. At enrollment, median serum sodium, uric acid, and potassium were 143 mmol/l, 6.3 mg/dl, 4.5 meq/l, respectively among women; and 143 mmol/l, 6.9 mg/dl, 4.3 meq/l among men. Mean slope of eGFR decline was -0.5 (SD 4.9) ml/min/yr. In exploratory analyses, men with greater years of education and those living in northern region of the study area experienced lower likelihood of disease progression (hazard ratios [HR] 0.87 [0.77-0.98] per additional year and 0.33 [0.12-0.89] for northern versus other subregions, respectively). There was a suggestion that men drinking well water had higher likelihood and men living further away from reservoirs had lower likelihood of >30% decline in eGFR (HR 2.07 [0.95-4.49] for drinking well water versus not, and HR 0.58 [0.32-1.05] per kilometer distance, respectively).The overall rate of kidney function decline was slow in this CKDu cohort, similar to other nonalbuminuric CKD, and event rates were similar among men and women. Further etiologic investigations could focus on specific residence locale and water use.

    View details for DOI 10.1016/j.ekir.2023.04.010

    View details for PubMedID 37441476

    View details for PubMedCentralID PMC10334401

  • Age-related decline in anti-HBV antibodies in vaccinated kidney transplant recipients. Transplant infectious disease : an official journal of the Transplantation Society Dadhania, D. M., Cravedi, P., Blumberg, E., Stryniak, G., Montez-Rath, M. E., Maltzman, J. S. 2023: e14090

    Abstract

    Hepatitis B virus (HBV) vaccination is indicated for all end stage kidney disease patients, including all solid organ transplant candidates. Maintenance of adequate immunity is especially important for immunosuppressed solid organ recipients who are at increased risk for donor or community acquired HBV. The impact of age and immunosuppression on long-term maintenance of HBV immunity postvaccination has not been fully investigated.We performed a single-center retrospective study of 96 kidney transplant recipients, transplanted between July 2012 and December 2020, who had Hepatitis B surface antibody (HBsAb) levels measured pretransplantation and 1-year posttransplantation. We compared the change in HBsAb levels stratified by patient's age (<45, 45-60, and >60) and by whether or not the patient received lymphocyte depleting induction therapy.Our results demonstrate that HBsAb IgG levels vary by age group, decreased significantly at 1-year posttransplant (p < .0001) and were significantly lower in the older cohort (p = .03). Among recipients who received rabbit anti-thymocyte globulin induction (rATG), the log HbsAb levels were significantly lower in the older age group (2.15 in age <45, 1.75 in age 45-60 and 1.47 in age >60, p = .01). Age group (p = .004), recipient HBcAb status (p = .002), and rATG (p = .048) were independently associated with >20% reduction in log HBsAb levels posttransplant.Significant declines in HBsAb levels occur postkidney transplantation, especially in older individuals, thus placing exposed older kidney transplant recipients at greater risk of HBV infection and associated complications.

    View details for DOI 10.1111/tid.14090

    View details for PubMedID 37377328

  • Hypocitraturia and Risk of Bone Disease in Patients With Kidney Stone Disease JBMR PLUS Ganesan, C., Thomas, I., Montez-Rath, M. E., Chertow, G. M., Leppert, J. T., Pao, A. C. 2023

    View details for DOI 10.1002/jbm4.10786

    View details for Web of Science ID 001018463200001

  • 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

  • Kidney Stone Events after Kidney Transplant in the United States. Clinical journal of the American Society of Nephrology : CJASN Ganesan, C., Holmes, M., Liu, S., Montez-Rath, M., Conti, S., Chang, T. C., Lenihan, C. R., Cheng, X. S., Chertow, G. M., Leppert, J. T., Pao, A. C. 2023

    Abstract

    BACKGROUND: Kidney stone disease is common and can lead to complications such as acute kidney injury, urinary tract obstruction, and urosepsis. In kidney transplant recipients, complications from kidney stone events can also lead to rejection and allograft failure. There is limited information on the incidence of kidney stone events in transplant recipients.METHODS: We identified 83,535 patients from the United States Renal Data System who received their first kidney transplant between January 1st, 2007 and December 31st, 2018. We examined the incidence of kidney stone events and identified risk factors associated with a kidney stone event in the first 3 years after transplantation.RESULTS: We found 1,436 (1.7%) patients who were diagnosed with a kidney stone in the 3 years following kidney transplant. The unadjusted incidence rate for a kidney stone event was 7.8 per 1000 person-years. The median time from transplant to a kidney stone diagnosis was 0.61 (25%,75% range 0.19-1.46) years. Patients with a prior history of kidney stones were at greatest risk for a kidney stone event after transplant (HR 4.65; 95% CI, 3.82-5.65). Other notable risk factors included a diagnosis of gout (HR 1.53; 95% CI, 1.31-1.80), hypertension (HR 1.29; 95% CI, 1.00-1.66), and a dialysis of vintage of > 9 years (HR 1.48; 95% CI, 1.18-1.86; ref vintage < 2.5 years).CONCLUSIONS: Approximately 2% of kidney transplant recipients were diagnosed with a kidney stone in the 3 years following kidney transplant. Risk factors for a kidney stone event include a prior history of kidney stones and longer dialysis vintage.

    View details for DOI 10.2215/CJN.0000000000000176

    View details for PubMedID 37071657

  • Feasibility and Acceptability of SARS-CoV-2 Screening among Patients Receiving Hemodialysis: A Pilot Study. Clinical journal of the American Society of Nephrology : CJASN Anand, S., Montez-Rath, M., Varkila, M., Yu, X., Block, M., Brillhart, S., Leppink, A., Hunsader, P., Owens, D. K., Chertow, G. M., Parsonnet, J., Block, G. 2023

    View details for DOI 10.2215/CJN.0000000000000137

    View details for PubMedID 36976655

  • Use of wastewater metrics to track COVID-19 in the U.S.: a national time-series analysis over the first three quarters of 2022. medRxiv : the preprint server for health sciences Varkila, M., Montez-Rath, M., Salomon, J., Yu, X., Block, G., Owens, D. K., Chertow, G. M., Parsonnet, J., Anand, S. 2023

    Abstract

    Widespread use of at-home COVID-19 tests hampers determination of community COVID-19 incidence. Using nationwide data available through the US National Wastewater Surveillance System, we examined the performance of two wastewater metrics in predicting high case and hospitalizations rates both before and after widespread use of at-home tests.We performed area under the receiver operating characteristic (ROC) curve analysis (AUC) for two wastewater metrics-viral concentration relative to the peak of January 2022 ("wastewater percentile") and 15-day percent change in SARS-CoV-2 ("percent change"). Dichotomized reported cases (≥ 200 or <200 cases per 100,000) and new hospitalizations (≥ 10 or <10 per 100,000) were our dependent variables, stratified by calendar quarter. Using logistic regression, we assessed the performance of combining wastewater metrics.Among 268 counties across 22 states, wastewater percentile detected high reported case and hospitalizations rates in the first quarter of 2022 (AUC 0.95 and 0.86 respectively) whereas the percent change did not (AUC 0.54 and 0.49 respectively). A wastewater percentile of 51% maximized sensitivity (0.93) and specificity (0.82) for detecting high case rates. A model inclusive of both metrics performed no better than using wastewater percentile alone. The predictive capability of wastewater percentile declined over time (AUC 0.84 and 0.72 for cases for second and third quarters of 2022).Nationwide, county wastewater levels above 51% relative to the historic peak predicted high COVID rates and hospitalization in the first quarter of 2022, but performed less well in subsequent quarters. Decline over time in predictive performance of this metric likely reflects underreporting of cases, reduced testing, and possibly lower virulence of infection due to vaccines and treatments.

    View details for DOI 10.1101/2023.02.06.23285542

    View details for PubMedID 36798337

    View details for PubMedCentralID PMC9934789

  • Associations of Serum and Dialysate Potassium Concentrations With Incident Atrial Fibrillation in a Cohort Study of Older US Persons Initiating Hemodialysis for Kidney Failure. Kidney international reports Hu, A., Liu, S., Montez-Rath, M. E., Khairallah, P., Niu, J., Turakhia, M. P., Chang, T. I., Winkelmayer, W. C. 2023; 8 (2): 305-316

    Abstract

    Introduction: Atrial fibrillation (AF) disproportionally affects persons on maintenance hemodialysis (HD). Associations of serum and dialysate potassium concentrations [K+] with AF incidence are poorly understood.Methods: We conducted a cohort study using Medicare claims merged with clinical data from a dialysis provider to determine whether serum-[K+] and/or dialysate-[K+] independently associated with AF incidence. Persons insured by fee-for-service Medicare aged≥67 years at dialysis initiation and free from diagnosed AF prior to day 120 of dialysis were eligible. Serum-[K+] and dialysate-[K+] were assessed in 30-day intervals and patients were followed-up with for AF incidence in subsequent 30-day intervals.Results: During 2006 to 2011, 15,190 persons (mean age= 76.3 years) initiating HD had no prior AF diagnosis. Mean serum-[K+] was 4.5 mEq/l; dialysate-[K+] was 3 mEq/l in 34% and 2 mEq/l in 52% of patients. Followed-up over 21,907 person-years, 2869 persons had incident AF (incidence/100 person-years, 13.1 [95% confidence interval [CI], 12.6-13.6]). The multivariable-adjusted association of serum-[K+] with incident AF was J-shaped as follows: relative to a serum-[K+] of 4.5 mEq/l, lower serum-[K+] associated with increased AF risk, whereas confidence bands for higher serum-[K+] indicated no association. Dialysis against a dialysate-[K+] of 3 mEq/l versus 2 mEq/l independently associated with a 14% (95% CI, 5%-24%) lower incidence of AF. No effect modification between serum-[K+] and dialysate-[K+] was detected (P= 0.34).Conclusion: Lower serum-[K+] was independently associated with incident AF whereas elevated serum-[K+] was not. The findings support adoption of dialysate solutions with a dialysate-[K+] of 3 mEq/l, regardless of patients' serum-[K+], and elimination of lower dialysate-[K+] solutions from practice. Clinical trials randomizing patients to different dialysate-[K+] are warranted to establish causality.

    View details for DOI 10.1016/j.ekir.2022.11.003

    View details for PubMedID 36815107

  • Association between cause of kidney failure and fracture incidence in a national US dialysis population cohort study. Clinical kidney journal Ziolkowski, S., Liu, S., Montez-Rath, M. E., Denburg, M., Winkelmayer, W. C., Chertow, G. M., O'Shaughnessy, M. M. 2022; 15 (12): 2245-2257

    Abstract

    Whether fracture rates, overall and by fracture site, vary by cause of kidney failure in patients receiving dialysis is unknown.Using the US Renal Data System, we compared fracture rates across seven causes of kidney failure in patients who started dialysis between 1997 and 2014. We computed unadjusted and multivariable adjusted proportional sub-distribution hazard models, with fracture events (overall, and by site) as the outcome and immunoglobulin A nephropathy as the reference group. Kidney transplantation and death were competing events.Among 491 496 individuals, with a median follow-up of 2.0 (25%, 75% range 0.9-3.9) years, 62 954 (12.8%) experienced at least one fracture. Patients with diabetic nephropathy, vasculitis or autosomal polycystic kidney disease (ADPKD) had the highest (50, 46 and 40 per 1000 person-years, respectively), and patient with lupus nephritis had the lowest (20 per 1000 person-years) fracture rates. After multivariable adjustment, diabetic nephropathy [hazard ratio (HR) 1.43, 95% confidence interval 1.33-1.53], ADPKD (HR 1.37, 1.26-1.48), vasculitis (HR 1.22, 1.09-1.34), membranous nephropathy (HR 1.16, 1.02-1.30) and focal segmental glomerulosclerosis (FSGS) (HR 1.13, 1.02-1.24) were associated with a significantly higher, and lupus nephritis with a significantly lower (HR 0.85, 0.71-0.98) fracture hazard. The hazards for upper extremity and lower leg fractures were significantly higher in diabetic nephropathy, ADPKD, FSGS and membranous nephropathy, while the hazard for vertebral fracture was significantly higher in vasculitis. Our findings were limited by the lack of data on medication use and whether fractures were traumatic or non-traumatic, among other factors.Fracture risk, overall and by fracture site, varies by cause of end-stage kidney disease. Future work to determine underlying pathogenic mechanisms contributing to differential risks might inform more tailored treatment strategies. Our study was limited by lack of data regarding numerous potential confounders or mediators including medications and measures or bone biomarkers.

    View details for DOI 10.1093/ckj/sfac193

    View details for PubMedID 36381373

    View details for PubMedCentralID PMC9664571

  • 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
  • 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

  • Parathyroidectomy and Cinacalcet Use in Medicare-Insured Kidney Transplant Recipients. American journal of kidney diseases : the official journal of the National Kidney Foundation Wang, A. X., Liu, S., Montez-Rath, M. E., Chertow, G. M., Lenihan, C. R. 2022

    Abstract

    RATIONALE & OBJECTIVE: Post-transplant hyperparathyroidism is common and treatment practices are poorly characterized. The goal of this study was to examine the incidence, associations, and outcomes of post-transplant parathyroidectomy and calcimimetic use in a cohort of Medicare-insured US kidney transplant recipients.STUDY DESIGN: Retrospective observational cohort study.SETTING & PARTICIPANTS: We used the US Renal Data System to extract demographic, clinical, and prescription data from Medicare Parts A, B and D-insured patients who received their first kidney transplant between 2007 and 2013. We excluded patients with pre-transplant parathyroidectomy.PREDICTORS: Calendar year of transplantation and pre-transplant patient characteristics.OUTCOMES: 1) Incidence of and secular trends in parathyroidectomy and cinacalcet use in the 3 years following transplant, 2) 90-day outcomes following post-transplant parathyroidectomy and cinacalcet initiation.ANALYTICAL APPROACH: Temporal trends and pre-transplant correlates of parathyroidectomy and cinacalcet use were assessed using proportional hazards models and multivariable Poisson regression, respectively.RESULTS: 30,127 patients met the inclusion criteria. 10,707 used cinacalcet pre-transplant. 551 patients underwent post-transplant parathyroidectomy and 5413 patients filled ≥ 1 prescription for cinacalcet. The rate of post-transplant parathyroidectomy was stable over time. In contrast, cinacalcet use increased during the period studied. Long dialysis vintage and pre-transplant cinacalcet use were strongly associated with post-transplant parathyroidectomy and cinacalcet use. Roughly one in four patients were hospitalized within 90 days of post-transplant parathyroidectomy, with hypocalcemia-related diagnoses being the most common complication. Parathyroidectomy (versus cinacalcet initiation) was not associated with an increase in acute kidney injury.LIMITATIONS: We lacked access to laboratory data to help assess severity of secondary/tertiary hyperparathyroidism. The cohort was limited to Medicare beneficiaries.CONCLUSIONS: Almost one fifth of our study cohort was treated with parathyroidectomy and/or cinacalcet. Further studies are needed to establish the optimal treatment for post-transplant hyperparathyroidism.

    View details for DOI 10.1053/j.ajkd.2022.07.015

    View details for PubMedID 36162617

  • Association between cause of kidney failure and fracture incidence in a national US dialysis population cohort study CLINICAL KIDNEY JOURNAL Ziolkowski, S., Liu, S., Montez-Rath, M. E., Denburg, M., Winkelmayer, W. C., Chertow, G. M., O'Shaughnessy, M. M. 2022
  • SARS-CoV-2 Booster Vaccine Response among Patients Receiving Dialysis. Clinical journal of the American Society of Nephrology : CJASN Garcia, P., Han, J., Montez-Rath, M., Sun, S., Shang, T., Parsonnet, J., Chertow, G., Anand, S., Schiller, B., Abra, G. 2022

    Abstract

    N/A.

    View details for DOI 10.2215/CJN.00890122

    View details for PubMedID 35383042

  • Cardiovascular outcomes associated with prescription of SGLT-2 inhibitors versus DPP-4 inhibitors in patients with diabetes mellitus and chronic kidney disease. Diabetes, obesity & metabolism Rhee, J. J., Han, J., Montez-Rath, M. E., Kim, S. H., Cullen, M. R., Stafford, R. S., Winkelmayer, W. C., Chertow, G. M. 1800

    Abstract

    AIMS: To determine the association with cardiovascular (CV) outcomes of sodium glucose cotransporter-2 (SGLT-2) inhibitors compared with dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).MATERIALS AND METHODS: We conducted a population-based cohort study of new users of SGLT-2 inhibitors and DPP-4 inhibitors with T2DM and CKD using data from Optum Clinformatics DataMart. We assembled three cohorts: T2DM/no CKD, T2DM/CKD 1-2, and T2DM/ CKD 3a. Study outcomes were 1) time to first heart failure (HF) hospitalization; and 2) time to a composite CV endpoint comprised of non-fatal myocardial infarction (MI) or stroke. After inverse probability of treatment weighting, we used proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI).RESULTS: New users of SGLT-2 inhibitors versus of DPP-4 inhibitors had lower risks of HF hospitalization in the T2DM/no CKD (HR, 0.76; 95% CI, 0.70, 0.82) and T2DM/CKD 1-2 (HR, 0.63; 95% CI, 0.48, 0.84), but no significant association was present in the T2DM/CKD 3a cohort. Compared with prescription of DPP-4 inhibitors, SGLT-2 inhibitors were associated with lower risks of non-fatal MI or stroke of 23% (HR, 0.77; 95% CI, 0.70, 0.85) in the T2DM/no CKD cohort, but no significant associations were present in the T2DM/CKD 1-2 and T2DM/CKD 3a cohorts.CONCLUSIONS: Incident prescription of SGLT-2 inhibitors was associated with lower risks of HF hospitalization but not with non-fatal MI or stroke despite suggesting benefit, relative to prescription of DPP-4 inhibitor across different stages of CKD. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/dom.14657

    View details for PubMedID 35118793

  • Transporting observational study results to a target population of interest using inverse odds of participation weighting. PloS one Ling, A. Y., Jreich, R., Montez-Rath, M. E., Meng, Z., Kapphahn, K., Chandross, K. J., Desai, M. 2022; 17 (12): e0278842

    Abstract

    Inverse odds of participation weighting (IOPW) has been proposed to transport clinical trial findings to target populations of interest when the distribution of treatment effect modifiers differs between trial and target populations. We set out to apply IOPW to transport results from an observational study to a target population of interest. We demonstrated the feasibility of this idea with a real-world example using a nationwide electronic health record derived de-identified database from Flatiron Health. First, we conducted an observational study that carefully adjusted for confounding to estimate the treatment effect of fulvestrant plus palbociclib relative to letrozole plus palbociclib as a second-line therapy among estrogen receptor (ER)-positive, human epidermal growth factor receptor (HER2)-negative metastatic breast cancer patients. Second, we transported these findings to the broader cohort of patients who were eligible for a first-line therapy. The interpretation of the findings and validity of such studies, however, rely on the extent that causal inference assumptions are met.

    View details for DOI 10.1371/journal.pone.0278842

    View details for PubMedID 36520950

  • SARS-CoV-2 Vaccine Antibody Response and Breakthrough Infection in Patients Receiving Dialysis. Annals of internal medicine Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Cadden, L., Hunsader, P., Morgan, C., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Chertow, G. M., Parsonnet, J. 1800

    Abstract

    BACKGROUND: Whether breakthrough SARS-CoV-2 infections after vaccination are related to the level of postvaccine circulating antibody is unclear.OBJECTIVE: To determine longitudinal antibody-based response and risk for breakthrough infection after SARS-CoV-2 vaccination.DESIGN: Prospective study.SETTING: Nationwide sample from dialysis facilities.PATIENTS: 4791 patients receiving dialysis.MEASUREMENTS: Remainder plasma from a laboratory processing routine monthly tests was used to measure qualitative and semiquantitative antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. To evaluate whether peak or prebreakthrough RBD values were associated with breakthrough infection, a nested case-control analysis matched each breakthrough case patient to 5 control patients by age, sex, and vaccination month and adjusted for diabetes status and region of residence.RESULTS: Of the 4791 patients followed with monthly RBD assays, 2563 were vaccinated as of 14 September 2021. Among the vaccinated patients, the estimated proportion with an undetectable RBD response increased from 6.6% (95% CI, 5.5% to 7.8%) 14 to 30 days after vaccination to 20.2% (CI, 17.0% to 23.3%) 5 to 6 months after vaccination. Estimated median index values decreased from 91.9 (CI, 78.6 to 105.2) 14 to 30 days after vaccination to 8.4 (CI, 7.6 to 9.3) 5 to 6 months after vaccination. Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days before breakthrough infection. Compared with prebreakthrough index RBD values of 23 or higher (equivalent to ≥506 binding antibody units per milliliter), prebreakthrough RBD values less than 10 and values from 10 to less than 23 were associated with higher odds for breakthrough infection (rate ratios, 11.6 [CI, 3.4 to 39.5] and 6.0 [CI, 1.5 to 23.6], respectively).LIMITATIONS: Single measure of vaccine response; ascertainment of COVID-19 diagnosis from electronic health records.CONCLUSION: The antibody response to SARS-CoV-2 vaccination wanes rapidly in persons receiving dialysis. In this population, the circulating antibody response is associated with risk for breakthrough infection.PRIMARY FUNDING SOURCE: Ascend Clinical Laboratory.

    View details for DOI 10.7326/M21-4176

    View details for PubMedID 34904856

  • Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis: A Cluster Randomized Trial. Kidney360 Chang, T. I., Tatoian, E. T., Montez-Rath, M. E., Chertow, G. M. 2021; 2 (11): 1752-1760

    Abstract

    Background: We conducted this study to examine the effect of taking versus holding BP medications before hemodialysis on intradialytic hypotension (IDH).Methods: In this cluster randomized trial, each dialysis unit was randomly designated as TAKE or HOLD units. Participants within a TAKE unit were instructed to take all BP medications as prescribed, whereas participants within a HOLD unit were instructed to hold medications dosed more than once daily before hemodialysis. The intervention lasted for 4 weeks. We hypothesized that TAKE would be noninferior to HOLD on the primary outcome of asymptomatic IDH, defined as ≥30% of sessions with nadir systolic BP <90 mm Hg and on the following secondary outcomes: uncontrolled hypertension (predialysis systolic BP >160 mm Hg), failure to achieve dry weight, and shortened dialysis sessions.Results: We randomized 10 dialysis units in a 1:1 ratio to TAKE or HOLD, which included 65 participants in TAKE and 66 participants in HOLD. We did not show that TAKE was noninferior to HOLD for the primary IDH outcome (mean unadjusted difference of 8%; 95% CI, -3% to 19%). TAKE was superior to HOLD for the outcome of uncontrolled hypertension (mean unadjusted difference of -15%, 95% CI, -28% to -1%). TAKE was noninferior to HOLD for the outcomes of failure to achieve dry weight and shortened dialysis sessions.Conclusions: In this cluster randomized trial that randomized patients to either taking or holding BP medications before hemodialysis, a strategy of taking BP medications dosed more than once daily was not noninferior to holding BP medications for the primary outcome of IDH, but did reduce the occurrence of uncontrolled hypertension. Whether any potential benefit of holding BP medications on reducing IDH is offset by any potential harm related to higher predialysis BP remains to be seen.

    View details for DOI 10.34067/KID.0001922021

    View details for PubMedID 35373003

  • Contributions of Systolic and Diastolic Blood Pressures to Cardiovascular Outcomes in the ALLHAT Study. Journal of the American College of Cardiology Itoga, N. K., Tawfik, D. S., Montez-Rath, M. E., Chang, T. I. 2021; 78 (17): 1671-1678

    Abstract

    BACKGROUND: SBP and DBP have important associations with cardiovascular events, but are seldom considered simultaneously.OBJECTIVES: This study sought to simultaneously analyze systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements on the associated risk of a primary composite outcome of all-cause mortality, myocardial infarction (MI), congestive heart failure (CHF), or stroke.METHODS: This study analyzed ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) data, which randomized adults to chlorthalidone, amlodipine, or lisinopril. The authors evaluated the simultaneous association of repeated SBP and DBP measurements on the primary composite outcome, and each outcome using proportional hazards regression. The authors report hazard ratios using a "heat map" to represent high and low risk according to SBP and DBP combinations.RESULTS: During a median follow-up of 4.4 years (interquartile range: 3.6-5.4 years), 33,357 participants experienced 2,636 MIs, 866 CHF events, 936 strokes, and 3,700 deaths; 8,138 patients (24.4%) had at least 1 event. For the composite outcome, all-cause mortality, MI, and CHF, a U-shaped association was observed with SBP and DBP, but the SBP and DBP associated with the lowest hazards differed for each outcome. For example, SBP/DBP of 140-155/70-80mmHg was associated with the lowest HR for all-cause mortality, compared with 110-120/85-90mmHg for MI and 125-135/70-75mmHg for CHF. In contrast, the association of SBP and stroke was linear.CONCLUSIONS: The risk pattern of SBP and DBP differs by clinical outcomes, and the SBP and DBP associated with the lowest risk. Our results suggest individualization of blood pressure targets may depend in part on the cardiovascular event for which the patient is most at risk.

    View details for DOI 10.1016/j.jacc.2021.08.035

    View details for PubMedID 34674811

  • Functional Consequences of Memory Inflation after Solid Organ Transplantation. Journal of immunology (Baltimore, Md. : 1950) Higdon, L. E., Schaffert, S., Cohen, R. H., Montez-Rath, M. E., Lucia, M., Saligrama, N., Margulies, K. B., Martinez, O. M., Tan, J. C., Davis, M. M., Khatri, P., Maltzman, J. S. 2021

    Abstract

    CMV is a major infectious complication following solid organ transplantation. Reactivation of CMV leads to memory inflation, a process in which CD8 T cells expand over time. Memory inflation is associated with specific changes in T cell function, including increased oligoclonality, decreased cytokine production, and terminal differentiation. To address whether memory inflation during the first year after transplantation in human subjects alters T cell differentiation and function, we employed single-cell-matched TCRalphabeta and targeted gene expression sequencing. Expanded T cell clones exhibited a terminally differentiated, immunosenescent, and polyfunctional phenotype whereas rare clones were less differentiated. Clonal expansion occurring between pre- and 3 mo posttransplant was accompanied by enhancement of polyfunctionality. In contrast, polyfunctionality and differentiation state were largely maintained between 3 and 12 mo posttransplant. Highly expanded clones had a higher degree of polyfunctionality than rare clones. Thus, CMV-responsive CD8 T cells differentiated during the pre- to posttransplant period then maintained their differentiation state and functional capacity despite posttransplant clonal expansion.

    View details for DOI 10.4049/jimmunol.2100405

    View details for PubMedID 34551963

  • Evolution of Cytomegalovirus-Responsive T Cell Clonality following Solid Organ Transplantation. Journal of immunology (Baltimore, Md. : 1950) Higdon, L. E., Schaffert, S., Huang, H., Montez-Rath, M. E., Lucia, M., Jha, A., Saligrama, N., Margulies, K. B., Martinez, O. M., Davis, M. M., Khatri, P., Maltzman, J. S. 2021

    Abstract

    CMV infection is a significant complication after solid organ transplantation. We used single cell TCR alphabeta sequencing to determine how memory inflation impacts clonality and diversity of the CMV-responsive CD8 and CD4 T cell repertoire in the first year after transplantation in human subjects. We observed CD8 T cell inflation but no changes in clonal diversity, indicating homeostatic stability in clones. In contrast, the CD4 repertoire was diverse and stable over time, with no evidence of CMV-responsive CD4 T cell expansion. We identified shared CDR3 TCR motifs among patients but no public CMV-specific TCRs. Temporal changes in clonality in response to transplantation and in the absence of detectable viral reactivation suggest changes in the repertoire immediately after transplantation followed by an expansion with stable clonal competition that may mediate protection.

    View details for DOI 10.4049/jimmunol.2100404

    View details for PubMedID 34551964

  • The Association of Pre-Kidney Transplant Dialysis Modality with de novo Posttransplant Heart Failure CARDIORENAL MEDICINE Lenihan, C. R., Liu, S., Airy, M., Walther, C., Montez-Rath, M. E., Winkelmayer, W. C. 2021: 1-9

    Abstract

    Heart failure (HF) after kidney transplantation is a significant but understudied problem. Pretransplant dialysis modality could influence incident HF risk through differing cardiac stressors. However, whether pretransplant dialysis modality is associated with the development of posttransplant HF is unknown.We used the US Renal Data System to assemble a cohort of 27,701 patients who underwent their first kidney transplant in the USA between the years 2005 and 2012 and who had Medicare fee-for-service coverage for >6 months preceding their transplant date. Patients with any HF diagnosis prior to transplant were excluded. Detailed baseline patient characteristics and comorbidities were abstracted. The outcome of interest was de novo posttransplant HF. Pretransplant dialysis modality was defined as the dialysis modality used at the time of transplant. We conducted time-to-event analyses using Cox regression. Death was treated as a competing risk in the study's primary analysis. Graft failure was included as a time-varying covariate.Among eligible patients, 81% were treated with hemodialysis prior to transplant, and hemodialysis patients were more likely to be male, had a shorter dialysis vintage, and had more diabetes and vascular disease diagnoses. When adjusted for all available demographic and clinical data, pretransplant treatment with hemodialysis (vs. peritoneal dialysis) was associated with a 19% increased risk in de novo posttransplant HF, with sub-distribution HR 1.19 (95% CI: 1.09-1.29).Our results suggest that choice of pretransplant dialysis modality may impact the development of posttransplant HF.

    View details for DOI 10.1159/000518535

    View details for Web of Science ID 000694028800001

    View details for PubMedID 34515084

  • 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

  • Estimated SARS-CoV-2 Seroprevalence in US Patients Receiving Dialysis 1 Year After the Beginning of the COVID-19 Pandemic. JAMA network open Anand, S., Montez-Rath, M., Han, J., Cadden, L., Hunsader, P., Kerschmann, R., Beyer, P., Boyd, S. D., Garcia, P., Dittrich, M., Block, G. A., Parsonnet, J., Chertow, G. M. 2021; 4 (7): e2116572

    Abstract

    Importance: Seroprevalence studies complement data on detected cases and attributed deaths in assessing the cumulative spread of the SARS-CoV-2 virus.Objective: To estimate seroprevalence of SARS-CoV-2 antibodies in patients receiving dialysis and adults in the US in January 2021 before the widespread introduction of COVID-19 vaccines.Design, Setting, and Participants: This cross-sectional study used data from the third largest US dialysis organization (US Renal Care), which has facilities located nationwide, to estimate SARS-CoV-2 seroprevalence among US patients receiving dialysis. Remainder plasma (ie, plasma that would have otherwise been discarded) of all patients receiving dialysis at US Renal Care facilities from January 1 to 31, 2021, was tested for SARS-CoV-2 antibodies. Patients were excluded if they had a documented dose of SARS-CoV-2 vaccination or if a residence zip code was missing from electronic medical records. Crude seroprevalence estimates from this sample (January 2021) were standardized to the US adult population using the 2018 American Community Survey 1-year estimates and stratified by age group, sex, self-reported race/ethnicity, neighborhood race/ethnicity composition, neighborhood income level, and urban or rural status. These data and case detection rates were then compared with data from a July 2020 subsample of patients who received dialysis at the same facilities.Exposures: Age, sex, race/ethnicity, and region of residence as well as neighborhood race/ethnicity composition, poverty, population density, and urban or rural status.Main Outcomes and Measures: The spike protein receptor-binding domain total antibody assay (Siemens Healthineers; manufacturer-reported sensitivity of 100% and specificity of 99.8%) was used to estimate crude SARS-CoV-2 seroprevalence in the unweighted sample, and then the estimated seroprevalence rates for the US dialysis and adult populations were calculated, adjusting for age, sex, and region.Results: A total of 21 464 patients (mean [SD] age, 63.1 [14.2] years; 12 265 men [57%]) were included in the unweighted sample from January 2021. The patients were disproportionately older (aged 65-79 years, 7847 [37%]; aged ≥80 years, 2668 [12%]) and members of racial/ethnic minority groups (Hispanic patients, 2945 [18%]; non-Hispanic Black patients, 4875 [29%]). Seroprevalence of SARS-CoV-2 antibodies was 18.9% (95% CI, 18.3%-19.5%) in the sample, with a seroprevalence of 18.7% (95% CI, 18.1%-19.2%) standardized to the US dialysis population, and 21.3% (95% CI, 20.3%-22.3%) standardized to the US adult population. In the unweighted sample, younger persons (aged 18-44 years, 25.9%; 95% CI, 24.1%-27.8%), those who self-identified as Hispanic or living in Hispanic neighborhoods (25.1%; 95% CI, 23.6%-26.4%), and those living in the lowest-income neighborhoods (24.8%; 95% CI, 23.2%-26.5%) were among the subgroups with the highest seroprevalence. Little variability was observed in seroprevalence by geographic region, population density, and urban or rural status in the January 2021 sample (largest regional difference, 1.2 [95% CI, 1.1-1.3] higher odds of seroprevalence in residents of the Northeast vs West).Conclusions and Relevance: In this cross-sectional study of patients receiving dialysis in the US, fewer than 1 in 4 patients had evidence of SARS-CoV-2 antibodies 1 year after the first case of SARS-CoV-2 infection was detected in the US. Results standardized to the US population indicate similar prevalence of antibodies among US adults. Vaccine introduction to younger individuals, those living in neighborhoods with a large population of racial/ethnic minority residents, and those living in low-income neighborhoods may be critical to disrupting the spread of infection.

    View details for DOI 10.1001/jamanetworkopen.2021.16572

    View details for PubMedID 34251441

  • Post-vaccination SARS-CoV-2 infections and incidence of presumptive B.1.427/B.1.429 variant among healthcare personnel at a northern California academic medical center. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Jacobson, K. B., Pinsky, B. A., Montez Rath, M. E., Wang, H., Miller, J. A., Skhiri, M., Shepard, J., Mathew, R., Lee, G., Bohman, B., Parsonnet, J., Holubar, M. 2021

    Abstract

    BACKGROUND: Although mRNA-based SARS-CoV-2 vaccines report ≥90% efficacy, breakthrough infections occur. Little is known about the effectiveness of these vaccines against SARS-CoV-2 variants, including the highly-prevalent B.1.427/B.1.429 variant in California..METHODS: In this quality improvement project, we collected demographic and clinical information from post-vaccine SARS-CoV-2 cases (PVSCs), defined as health care personnel (HCP) with positive SARS-CoV-2 NAAT after receiving ≥1 vaccine dose. Available specimens were tested for L452R, N501Y and E484K mutations by RT-PCR. Mutation prevalence was compared among unvaccinated, early post-vaccinated (<=14 days after dose 1), partially vaccinated (positive test >14 days after dose 1 and ≤14 days after dose 2) and fully vaccinated (>14 days after dose 2) PVSCs.RESULTS: From December 2020-April 2021, >=23,090 HCPS received at least1 dose of an mRNA-based SARS-CoV-2 vaccine, and 660 HCP cases of SARS-CoV-2 occurred of which 189 were PVSCs. Among the PVSCs, 114 (60.3%), 49 (25.9%) and 26 (13.8%) were early post-vaccination, partially vaccinated, and fully vaccinated, respectively. Of 261 available samples from vaccinated and unvaccinated HCP, 103 (39.5%), including 42 PVSCs (36.5%), had L452R mutation presumed to be B.1.427/B.1.429,. When adjusted for community prevalence of B.1.427/B.1.429, PVSCs did not have significantly elevated risk for infection with B.1.427/B.1.429 compared with unvaccinated HCP.CONCLUSIONS: Most PVSCs occurred prior to expected onset of full, vaccine-derived immunity. Presumptive B.1.427/B.1.429 was not more prevalent in post-vaccine cases than in unvaccinated SARS-CoV-2 HCP. Continued infection control measures, particularly ≤14 days post-vaccination, and continued variant surveillance in PVSCs is imperative to control future SARS-CoV-2 surges.

    View details for DOI 10.1093/cid/ciab554

    View details for PubMedID 34137815

  • Antibody Response to COVID-19 Vaccination in Patients Receiving Dialysis. Journal of the American Society of Nephrology : JASN Anand, S., Montez-Rath, M., Han, J., Garcia, P., Cadden, L., Hunsader, P., Kerschmann, R., Beyer, P., Dittrich, M., Block, G., Boyd, S., Parsonnet, J., Chertow, G. 2021

    View details for DOI 10.1681/ASN.2021050611

    View details for PubMedID 34117129

  • Comparison of Pre-Amputation Evaluation in Patients with and without Chronic Kidney Disease. American journal of nephrology Subramanian, N., Han, J., Leeper, N. J., Ross, E. G., Montez-Rath, M. E., Chang, T. I. 2021: 1–8

    Abstract

    INTRODUCTION: Patients with chronic kidney disease (CKD) and peripheral artery disease (PAD) are more likely to undergo lower extremity amputation than patients with preserved kidney function. We sought to determine whether patients with CKD were less likely to receive pre-amputation care in the 1-year prior to lower extremity amputation compared to patients without CKD.METHODS: We conducted a retrospective observational study of patients with PAD-related lower extremity amputation between January 2014 and December 2017 using a large commercial insurance database. The primary exposure was CKD identified using billing codes and laboratory values. The primary outcomes were receipt of pre-amputation care, defined as diagnostic evaluation (ankle-brachial index, duplex ultrasound, and computed tomographic angiography), specialty care (vascular surgery, cardiology, orthopedic surgery, and podiatry), and lower extremity revascularization in the 1-year prior to amputation. We conducted separate logistic regression models to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) among patients with and without CKD. We assessed for effect modification by age, sex, Black race, and diabetes status.RESULTS: We identified 8,554 patients with PAD-related amputation. In fully adjusted models, patients with CKD were more likely to receive diagnostic evaluation (aOR 1.30; 95% CI 1.17-1.44) and specialty care (aOR 1.45, 95% CI 1.27-1.64) in the 1-year prior to amputation. There was no difference in odds of revascularization by CKD status (aOR 1.03, 0.90-1.19). Age, sex, Black race, and diabetes status did not modify these associations.DISCUSSION/CONCLUSION: Patients with CKD had higher odds of receiving diagnostic testing and specialty care and similar odds of lower extremity revascularization in the 1-year prior to amputation than patients without CKD. Disparities in access to pre-amputation care do not appear to explain the higher amputation rates seen among patients with CKD.

    View details for DOI 10.1159/000516017

    View details for PubMedID 33957619

  • Barriers to ACEI/ARB Use in Proteinuric Chronic Kidney Disease: An Observational Study. Mayo Clinic proceedings McCoy, I. E., Han, J., Montez-Rath, M. E., Chertow, G. M. 2021

    Abstract

    OBJECTIVE: To assess present angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use among patients with proteinuric chronic kidney disease (CKD) and examine barriers limiting this guideline-concordant care.PATIENTS AND METHODS: Using a nationwide database containing patient-level claims and integrated clinical information, we examined current ACEI/ARB prescriptions on the index date (April 15, 2017) and prior ACEI/ARB use in 41,743 insured adults with proteinuric CKD. Using multivariable logistic regression, we estimated adjusted associations between current ACEI/ARB use and putative barriers including past acute kidney injury (AKI), hyperkalemia, advanced CKD, and lack of nephrology care.RESULTS: Only 49% (n=20,641) of patients had an active ACEI/ARB prescription on the index date, but 87% (n=36,199) had been previously prescribed an ACEI/ARB. Use was lower in patients with past AKI, hyperkalemia, CKD stages 4 or 5, and a lack of nephrology care (adjusted odds ratios were 0.61 [95% CI, 0.58 to 0.64], 0.76 [95% CI, 0.72 to 0.80], 0.48 [95% CI, 0.45 to 0.51], and 0.85 [95% CI, 0.81 to 0.89], respectively).CONCLUSION: Discontinuing, rather than never initiating, ACEI/ARB treatment limits guideline-concordant care in proteinuric CKD. Past AKI, hyperkalemia, advanced CKD, and lack of nephrology care were associated with lower use of ACEIs/ARBs, but these putative barriers may in many instances be inappropriate (AKI and advanced CKD) or modifiable (hyperkalemia and lack of nephrology care).

    View details for DOI 10.1016/j.mayocp.2020.12.038

    View details for PubMedID 33952396

  • Ultrafiltration rate and incident atrial fibrillation among older individuals initiating hemodialysis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Flythe, J. E., Liu, S., Montez-Rath, M. E., Winkelmayer, W. C., Chang, T. I. 2021

    Abstract

    BACKGROUND: Higher ultrafiltration (UF) rates are associated with numerous adverse cardiovascular outcomes among individuals receiving maintenance hemodialysis. We undertook this study to investigate the association of UF rate and incident atrial fibrillation in a large, nationally representative US cohort of incident, older hemodialysis patients.METHODS: We used the US Renal Data System linked to the records of a large dialysis provider to identify individuals ≥67years of age initiating hemodialysis between January 2006 and December 2011. We applied an extended Cox model as a function of a time-varying exposure to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of delivered UF rate and incident atrial fibrillation.RESULTS: Among the 15414 individuals included in the study, 3177 developed atrial fibrillation. In fully adjusted models, a UF rate >13mL/h/kg (versus ≤13mL/h/kg) was associated with a higher hazard of incident atrial fibrillation [adjusted HR 1.19 (95% CI 1.07-1.30)]. Analyses using lower UF rate thresholds (≤10 versus >10mL/h/kg and ≤8 versus >8mL/h/kg, separately) yielded similar results. Analyses specifying the UF rate as a cubic spline (per 1mL/h/kg) confirmed an approximately linear dose-response relationship between the UF rate and the risk of incident atrial fibrillation: risk began at UF rates of ~6mL/h/kg and the magnitude of this risk flattened, but remained elevated, at rates ≥9mL/h/kg.CONCLUSION: In this observational study of older individuals initiating hemodialysis, higher UF rates were associated with higher incidences of atrial fibrillation.

    View details for DOI 10.1093/ndt/gfaa332

    View details for PubMedID 33561218

  • Using kinetic eGFR to identify acute kidney injury risk in children undergoing cardiac transplantation. Pediatric research Dasgupta, M. N., Montez-Rath, M. E., Hollander, S. A., Sutherland, S. M. 2021

    Abstract

    Acute kidney injury (AKI) is common following pediatric cardiac transplantation. Since no treatments exist, strategies focus on early identification and prevention. Kinetic glomerular filtration rate (kGFR) was developed to assess renal function in the non-steady state. Although used to predict AKI in adults, kGFR has not been explored in children. Our study examines AKI and the ability of kGFR to identify AKI risk in pediatric heart transplant recipients.One hundred and seventy-five patients under 21 years who underwent cardiac transplantation at Lucile Packard Children's Hospital between September 2007-December 2017 were included. kGFR1 was calculated using pre-operative and immediate post-operative creatinines; kGFR2 was calculated with the first two post-operative creatinines. The primary outcome was AKI as defined by the Kidney Disease: Improving Global Outcomes criteria.One hundred and thirty-one (75%) and 78 (45%) patients developed AKI and severe AKI, respectively; 5 (2.9%) required dialysis. kGFR was moderately associated with post-operative AKI risk. The adjusted area under the curve (AUC) for kGFR1 was 0.72 (discovery) and 0.65 (validation). The AUC for kGFR2 was 0.72 (discovery) and 0.68 (validation).AKI is pervasive in children undergoing cardiac transplant, particularly in the 24 h after surgery. kGFR moderately identifies AKI risk and may represent a novel risk stratification technique.Our research suggests that kGFR, a dynamic assessment of renal function that uses readily available laboratory values, can moderately identify AKI risk in children undergoing cardiac transplantation. Current published studies on kGFR are in adult populations; this study represents the first formal study of kGFR in a pediatric population. kGFR may serve as an early AKI indicator, allowing providers to implement preventative strategies sooner in a patient's clinical course.

    View details for DOI 10.1038/s41390-020-01307-3

    View details for PubMedID 33446916

  • SARS-CoV-2 vaccine antibody response and breakthrough infection in dialysis. medRxiv : the preprint server for health sciences Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Cadden, L., Hunsader, P., Morgan, C., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Chertow, G. M., Parsonnet, J. 2021

    Abstract

    Patients receiving dialysis are a sentinel population for groups at high risk for death and disability from COVID-19. Understanding correlates of protection post-vaccination can inform immunization and mitigation strategies.Monthly since January 2021, we tested plasma from 4791 patients receiving dialysis for antibodies to the receptor-binding domain (RBD) of SARS-CoV-2 using a high-throughput assay. We qualitatively assessed the proportion without a detectable RBD response and among those with a response, semiquantitative median IgG index values. Using a nested case-control design, we matched each breakthrough case to five controls by age, sex, and vaccination-month to determine whether peak and pre-breakthrough RBD IgG index values were associated with risk for infection post-vaccination.Among 2563 vaccinated patients, the proportion without a detectable RBD response increased from 6.6% [95% CI 5.5-8.1] in 14-30 days post-vaccination to 20.2% [95% CI 17.1-23.8], and median index values declined from 92.7 (95% CI 77.8-107.5) to 3.7 (95% CI 3.1-4.3) after 5 months. Persons with SARS-CoV-2 infection prior-to-vaccination had higher peak index values than persons without prior infection, but values equalized by 5 months (p=0.230). Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days pre-breakthrough. Peak and pre-breakthrough RBD values <23 (equivalent to <506 WHO BAU/mL) were associated with higher odds for breakthrough infection (OR: 3.7 [95% CI 2.0-6.8] and 9.8 [95% CI 2.9-32.8], respectively).The antibody response to SARS-CoV-2 vaccination wanes rapidly, and in persons receiving dialysis, the persisting antibody response is associated with risk for breakthrough infection.

    View details for DOI 10.1101/2021.10.12.21264860

    View details for PubMedID 34671782

    View details for PubMedCentralID PMC8528091

  • Antibody Response to COVID-19 vaccination in Patients Receiving Dialysis. medRxiv : the preprint server for health sciences Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Cadden, L., Hunsader, P., Kerschmann, R., Beyer, P., Dittrich, M., Block, G. A., Boyd, S. D., Parsonnet, J., Chertow, G. M. 2021

    Abstract

    Patients receiving dialysis may mount impaired responses to COVID19 vaccination.We report antibody response to vaccination from 1140 patients without, and 493 patients with pre-vaccination SARS-CoV-2 RBD antibody. We used commercially available assays (Siemens) to test remainder plasma monthly in association with vaccination date and type, and assess prevalence of absent total receptor binding antibody, and absent or attenuated (index value < 10) semiquantitative receptor binding domain IgG index values. We used Poisson regression to evaluate risk factors for absent or attenuated response to vaccination.Among patients who were seronegative versus seropositive before vaccination, 62% and 56% were ≥65 years old, 20% and 24% were Hispanic, and 22% and 23% were Black. Median IgG index values rose steadily over time, and were higher among the seropositive than in the seronegative patients after completing vaccination (150 [25 th , 75 th percentile 23.2, 150.0] versus 41.6 [11.3, 150.0]). Among 610 patients who completed vaccination (assessed ≥14 days later, median 29 days later), the prevalence of absent total RBD response, and absent and attenuated semiquantitative IgG response was 4.4% (95% CI 3.1, 6.4%), 3.4% (2.4, 5.2%), and 14.3% (11.7, 17.3%) respectively. Risk factors for absent or attenuated response included longer vintage of end-stage kidney disease, and lower pre-vaccination serum albumin.More than one in five patients receiving dialysis had evidence of an attenuated immune response to COVID19 vaccination.Patients receiving dialysis face high likelihood of severe COVID19; at the same time, vaccination may be less efficacious, as prior data indicate impaired immune responses to influenza and Hepatitis B vaccination. We found that 22% of patients receiving dialysis had suboptimal responses to vaccination, irrespective of whether or not they had evidence of prior SARS-CoV-2 infection. Poorer health status and longer duration of end-stage kidney disease increased likelihood of suboptimal response. Ongoing vigilance for COVID19 in dialysis facilities and studies of modified vaccination dosing schedules will be critical to protecting patients receiving dialysis.

    View details for DOI 10.1101/2021.05.06.21256768

    View details for PubMedID 34013281

    View details for PubMedCentralID PMC8132255

  • Hemodynamic Predictors of Renal Function After Pediatric Left Ventricular Assist Device Implantation. ASAIO journal (American Society for Artificial Internal Organs : 1992) Chen, C. Y., Montez-Rath, M. E., May, L. J., Maeda, K., Hollander, S. A., Rosenthal, D. N., Krawczeski, C. D., Sutherland, S. M. 2021; 67 (12): 1335-1341

    Abstract

    Although renal function often improves after pediatric left ventricular assist device (LVAD) implantation, recovery is inconsistent. We aimed to identify hemodynamic parameters associated with improved renal function after pediatric LVAD placement. A single-center retrospective cohort study was conducted in patients less than 21 years who underwent LVAD placement between June 2004 and December 2015. The relationship between hemodynamic parameters and estimated glomerular filtration rate (eGFR) was assessed using univariate and multivariate modeling. Among 54 patients, higher preoperative central venous pressure (CVP) was associated with eGFR improvement after implantation (p = 0.012). However, 48 hours postimplantation, an increase in CVP from baseline was associated with eGFR decline over time (p = 0.01). In subgroup analysis, these associations were significant only for those with normal pre-ventricular assist device renal function (p = 0.026). In patients with preexisting renal dysfunction, higher absolute CVP values 48 and 72 hours after implantation predicted better renal outcome (p = 0.005). Our results illustrate a complex relationship between ventricular function, volume status, and renal function. Additionally, they highlight the challenge of using CVP to guide management of renal dysfunction in pediatric heart failure. Better methods for evaluating right heart function and volume status are needed to improve our understanding of how hemodynamics impact renal function in this population.

    View details for DOI 10.1097/MAT.0000000000001460

    View details for PubMedID 34860188

  • COVID19 vaccine type and humoral immune response in patients receiving dialysis. medRxiv : the preprint server for health sciences Garcia, P., Anand, S., Han, J., Montez-Rath, M., Sun, S., Shang, T., Parsonnet, J., Chertow, G. M., Schiller, B., Abra, G. 2021

    Abstract

    Patients on dialysis vaccinated with the attenuated adenovirus SARS-CoV-2 vaccine might mount an impaired response to vaccination.We evaluated the humoral vaccination response among 2,099 fully vaccinated patients receiving dialysis. We used commercially available assays (Siemens) to assess prevalence of no response or diminished response to COVID-19 vaccination by vaccine type. We defined "no seroconversion" as lack of change from negative to positive in total RBD Ig antibody, no detectable response on semiquantitative RBD IgG antibody (index value <1) as "no RBD IgG response", and a semiquantitative RBD IgG index value <10 as "diminished RBD IgG response".Of the 2,099 fully vaccinated patients on dialysis, the proportion receiving the mRNA1273, BNT162b2, and Ad26.COV2.S were 62% (n=1316), 20% (n=416) and 18% (n=367), respectively. A third (33.3%) of patients receiving the attenuated adenovirus Ad26.COV2.S vaccine failed to seroconvert and an additional 36% had no detectable or diminished IgG response even 28-60 days post vaccination.One in three fully vaccinated patients receiving dialysis had evidence of an impaired immune response to the attenuated adenovirus Ad26.COV2.S vaccine.

    View details for DOI 10.1101/2021.08.02.21261516

    View details for PubMedID 34373862

    View details for PubMedCentralID PMC8351784

  • Laboratory correlates of SARS-CoV-2 seropositivity in a nationwide sample of patients on dialysis in the U.S. PloS one Anand, S., Montez-Rath, M. E., Han, J., Garcia, P., Bozeman, J., Kerschmann, R., Beyer, P., Parsonnet, J., Chertow, G. M. 2021; 16 (4): e0249466

    Abstract

    Patients on dialysis are at high risk for death due to COVID-19, yet a significant proportion do survive as evidenced by presence of SARS-CoV-2 antibodies in 8% of patients in the U.S. in July 2020. It is unclear whether patients with seropositivity represent the subgroup with robust health status, who would be more likely to mount a durable antibody response. Using data from a July 2020 sample of 28,503 patients receiving dialysis, we evaluated the cross-sectional association of SARS-CoV-2 seropositivity with laboratory surrogates of patient health. In separate logistic regression models, we assessed the association of SARS-CoV-2 seropositivity with seven laboratory-based covariates (albumin, creatinine, hemoglobin, sodium, potassium, phosphate, and parathyroid hormone), across the entire range of the laboratory and in comparison to a referent value. Models accounted for age, sex, region, race and ethnicity, and county-level COVID-19 deaths per 100,000. Odds of seropositivity for albumin 3 and 3.5 g/dL were 2.1 (95% CI 1.9-2.3) and 1.3 (1.2-1.4) respectively, compared with 4 g/dL. Odds of seropositivity for serum creatinine 5 and 8 mg/dL were 1.8 (1.6-2.0) and 1.3 (1.2-1.4) respectively, compared with 12.5 mg/dL. Lower values of hemoglobin, sodium, potassium, phosphate, and parathyroid hormone were associated with higher odds of seropositivity. Laboratory values associated with poorer health status and higher risk for mortality were also associated with higher likelihood of SARS-CoV-2 antibodies in patients receiving dialysis.

    View details for DOI 10.1371/journal.pone.0249466

    View details for PubMedID 33857168

  • 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

  • Intradialytic Hypotension and Newly Recognized Peripheral Artery Disease in Patients Receiving Hemodialysis. American journal of kidney diseases : the official journal of the National Kidney Foundation Seong, E. Y., Liu, S., Song, S. H., Leeper, N. J., Winkelmayer, W. C., Montez-Rath, M. E., Chang, T. I. 2020

    Abstract

    RATIONALE & OBJECTIVE: Intradialytic hypotension (IDH) may decrease systemic circulation to the legs, exacerbating symptoms of peripheral artery disease (PAD). We sought to evaluate the relationship between IDH and newly recognized lower extremity PAD among hemodialysis patients STUDY DESIGN: Retrospective cohort study.SETTING & PARTICIPANTS: Linking the data from USRDS to the electronic health records of a large dialysis provider, we identified adults patients (≥18 years) with Medicare Parts A and B who initiated dialysis (2006-2011) without previously recognized PAD.EXPOSURE: Time-varying proportion of hemodialysis sessions with IDH defined as nadir intradialytic systolic blood pressure <90 mmHg. We categorized the proportion of sessions with IDH within serial 30-day intervals as 0%, >0-<15%, 15-<30%, and ≥30%.OUTCOME: Newly recognized PAD, ascertained using PAD diagnosis codes and procedure codes for amputation or revascularization, in serial 30-day intervals subsequent to each 30-day exposure interval.ANALYTIC APPROACH: To account for the competing risks of death and kidney transplantation, we estimated unadjusted and adjusted sub-distribution hazard ratios using the Kaplan-Meier multiple imputation method in combination with the extended Cox model to account for IDH as a time-varying exposure.RESULTS: Among 45,591 patients, those with more frequent baseline IDH had a higher prevalence of cardiovascular diseases. During 61,725 person-years of follow-up, 7,886 patients had newly recognized PAD. We found a graded, direct association of IDH with newly recognized PAD. For example, having IDH in ≥30% of dialysis sessions during a given 30-day interval (versus 0%) was associated with a 24% higher hazard of having newly recognized PAD (95% CI, 17% to 32%) in the subsequent 30 days.LIMITATIONS: Unmeasured confounding; ascertainment of PAD from claims CONCLUSIONS: Patients receiving hemodialysis who had more frequent IDH had higher rates of newly recognized PAD. Patients with frequent IDH may warrant careful examination for PAD.

    View details for DOI 10.1053/j.ajkd.2020.10.012

    View details for PubMedID 33316351

  • Comparison Between Ticagrelor and Clopidogrel in Elderly Patients with an Acute Coronary Syndrome: Insights from the SWEDEHEART Registry. Circulation Szummer, K., Montez-Rath, M. E., Alfredsson, J., Erlinge, D., Lindahl, B., Hofmann, R., Ravn-Fischer, A., Svensson, P., Jernberg, T. 2020

    Abstract

    Background: The comparative efficacy and safety of ticagrelor vs. clopidogrel in older myocardial infarction (MI) patients has received limited study. Methods: We performed an observational analysis of all patients ≥80 years (n=14005) who were discharged alive with aspirin combined with either clopidogrel (60.2%) or ticagrelor (39.8%) after a MI between 2010 and 2017 registered in the national registry Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). Inverse probability treatment weighting was used in Cox regression models to adjust for differences in demographics, in-hospital therapies, and medications. The primary ischemic outcome (death, MI or stroke), and bleeding were obtained from national registries at 1 year. A sensitivity analysis in <80-year-old patients was performed. Results: In patients ≥80 years, the incidence of the primary ischemic outcome (HR 0.97, 95% CI 0.88-1.06) was similar for ticagrelor- and clopidogrel-treated patients. Ticagrelor was associated with a 17% and 48% higher risk of death (1.17 (1.03- 1.32)) and bleeding (1.48 (1.25- 1.76)), but a lower risk of MI (0.80 (0.70- 0.92)) and stroke (0.72 (0.56-0.93)). In <80-year-old patients the incidence of the primary ischemic outcome was 17% (0.83 (0.77-0.89)) lower with ticagrelor. Ticagrelor was associated with 15% (0.85 (0.76-0.96)) lower risk of death, 32% higher risk of bleeding (1.32 (1.18-1.47)), but lower risk of MI (0.82 (0.75-0.91)) and stroke (0.82 (0.69-0.98)). Conclusions: Ticagrelor use among elderly MI patients was associated with higher risk of bleeding and death compared with clopidogrel. A randomized study of ticagrelor vs clopidogrel in the elderly is needed.

    View details for DOI 10.1161/CIRCULATIONAHA.120.050645

    View details for PubMedID 32867508

  • Drug Development in Kidney Disease: Proceedings From a Multistakeholder Conference. American journal of kidney diseases : the official journal of the National Kidney Foundation Edmonston, D. L., Roe, M. T., Block, G., Conway, P. T., Dember, L. M., DiBattiste, P. M., Greene, T., Hariri, A., Inker, L. A., Isakova, T., Montez-Rath, M. E., Nkulikiyinka, R., Polidori, D., Roessig, L., Tangri, N., Wyatt, C., Chertow, G. M., Wolf, M. 2020

    Abstract

    Occasional bursts of discovery and innovation have appeared during the otherwise stagnant past several decades of drug development in nephrology. Among other recent drug discoveries, the unexpected kidney benefits observed with sodium-glucose cotransporter-2 inhibitors may herald a renaissance of drug development in kidney disease. This recent progress highlights the need to further promote and stimulate research and development of promising therapies that may ameliorate the morbidity and mortality associated with kidney disease. To help identify and address barriers to drug development in nephrology, the Duke Clinical Research Institute convened a think tank in April 2019 that included stakeholders from academia, industry, government agencies, and patient advocacy. From these discussions, several opportunities were identified to improve every stage of drug development for kidney disease from early discovery to implementation into practice. Key topics reviewed in this article are the utility of interconnected data and site research networks, surrogate endpoints, pragmatic and adaptive trial designs, the promising uses of real-world data, and methods to improve the generalizability of trial results and uptake of approved drugs for kidney-related diseases.

    View details for DOI 10.1053/j.ajkd.2020.05.026

    View details for PubMedID 32768631

  • Does really central venous pressure affect the risk of diuretic-associated acute kidney injury after cardiac surgery? American heart journal McCoy, I., Montez-Rath, M., Chertow, G., Chang, T. 2020; 226: 252

    View details for DOI 10.1016/j.ahj.2020.04.002

    View details for PubMedID 32811639

  • Hip Fracture Risk among Hemodialysis-Dependent Patients Prescribed Opioids and Gabapentinoids. Journal of the American Society of Nephrology : JASN Vangala, C., Niu, J., Montez-Rath, M. E., Yan, J., Navaneethan, S. D., Naik, A. D., Winkelmayer, W. C. 2020

    Abstract

    BACKGROUND: Despite opioids' known association with hip fracture risk in the general population, they are commonly prescribed to patients with ESKD. Whether use of opioids or gabapentinoids (also used to treat pain in patients with ESKD) contributes to hip fracture risk in patients with ESKD on hemodialysis remains unknown.METHODS: In a case-control study nested within the US Renal Data System, we identified all hip fracture events recorded among patients dependent on hemodialysis from January 2009 through September 2015. Eligible cases were risk-set matched on index date with ten eligible controls. We required >1 year of Medicare Parts A and B coverage and >3 years of part D coverage to study cumulative longer-term exposure. To examine new, short-term exposure, we selected individuals with >18 months of Part D coverage and no prior opioid or gabapentinoid use between 18 and 7 months before index. We used conditional logistic regression to estimate unadjusted and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CI).RESULTS: For the longer-term analyses, we identified 4912 first-time hip fracture cases and 49,120 controls. Opioid use was associated with increased hip fracture risk (adjusted OR, 1.39; 95% CI, 1.26 to 1.53). Subgroups of low, moderate, and high use yielded adjusted ORs of 1.33 (95% CI, 1.20 to 1.47), 1.53 (95% CI, 1.36 to 1.72), and 1.66 (95% CI, 1.45 to 1.90), respectively. The association with hip fractures was also elevated with new, short-term use (adjusted OR, 1.38; 95% CI, 1.25 to 1.52). There were no associations between gabapentinoid use and hip fracture.CONCLUSIONS: Among patients dependent on hemodialysis in the United States, both short-term and longer-term use of opioid analgesics were associated with hip fracture events.

    View details for DOI 10.1681/ASN.2019090904

    View details for PubMedID 32371535

  • Patient and Provider Characteristics Associated With Sodium-Glucose Cotransporter 2 Inhibitor Prescription in Patients With Diabetes and Proteinuric Chronic Kidney Disease. Clinical diabetes : a publication of the American Diabetes Association McCoy, I. E., Han, J. n., Montez-Rath, M. E., Chertow, G. M., Rhee, J. J. 2020; 38 (3): 240–47

    Abstract

    Despite accumulating evidence of cardiorenal benefits from sodium-glucose cotransporter 2 (SGLT2) inhibitors, prescription of agents in this drug class may be limited by concerns regarding adverse effects and interdisciplinary care coordination. To investigate these potential barriers, we performed a cross-sectional study of SGLT2 inhibitor prescriptions in 2017 in 3,779 adults with type 2 diabetes and proteinuric chronic kidney disease from a nationwide database. Only 173 (5%) of these patients received an SGLT2 inhibitor in 2017. Younger age, renin-angiotensin-aldosterone system inhibitor prescription, and higher estimated glomerular filtration rate were associated with SGLT2 inhibitor prescription. Primary care providers were responsible for the majority of the prescriptions. Continued efforts should be made to track and improve SGLT2 inhibitor use in indicated populations.

    View details for DOI 10.2337/cd19-0087

    View details for PubMedID 32699472

    View details for PubMedCentralID PMC7364452

  • Glycemic Control and Infections Among US Hemodialysis Patients With Diabetes Mellitus. Kidney international reports Rhee, J. J., Zheng, Y. n., Liu, S. n., Montez-Rath, M. E., Hamill, R. J., Ishida, J. H., Winkelmayer, W. C. 2020; 5 (7): 1014–25

    Abstract

    Patients with diabetes mellitus (DM) on hemodialysis (HD) may be particularly vulnerable to infections.We used merged data from the United States Renal Data System and electronic health records data from a large US dialysis provider to retrospectively examine the association between glycemic control and infections in these patients. Adult patients with DM aged ≥18 years who initiated in-center maintenance HD treatment from 2006 to 2011 and survived >90 days were included. Quarterly mean time-averaged hemoglobin A1c (HbA1c) values were categorized into <5.5%, 5.5 to <6.5%, 6.5 to <7.5%, 7.5 to <8.5%, and ≥8.5%. We used Medicare claims to ascertain infection-related outcomes and the ESRD Death Notification to identify death from infectious cause. We used Cox proportional hazards models to estimate multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) for the associations between time-averaged HbA1c categories and infectious events.In a cohort of 33,753 eligible patients, those with higher HbA1c levels had higher rates of diabetic foot infections and skin and soft tissue infections, with patients with HbA1c ≥8.5% having 23% (95% CI, 5%, 45%) and 22% (95% CI, 5%, 42%) higher rates, respectively, compared with HbA1c 5.5 to <6.5%. Patients in the lower HbA1c categories had higher rates of infection-related and all-cause mortality (P-for-trend <0.001).This study highlights the need for greater attention to foot evaluation and skin and soft tissue infections among patients on HD with less than optimal diabetes control.

    View details for DOI 10.1016/j.ekir.2020.04.020

    View details for PubMedID 32647759

    View details for PubMedCentralID PMC7335954

  • Antidiabetic medication use in patients with type 2 diabetes and chronic kidney disease JOURNAL OF DIABETES AND ITS COMPLICATIONS Rhee, J. J., Han, J., Montez-Rath, M. E., Kim, S. H., Cullen, M. R., Stafford, R. S., Winkelmayer, W. C., Chertow, G. M. 2019; 33 (11)
  • Trends in the Medical Complexity and Outcomes of Medicare-insured Patients Undergoing Kidney Transplant in the Years 1998-2014 TRANSPLANTATION Lenihan, C. R., Liu, S., Montez-Rath, M. E., Winkelmayer, W. C. 2019; 103 (11): 2413–22

    Abstract

    Graft and patient survival following kidney transplant are improving. However, the drivers of this trend are unclear. To gain further insight, we set out to examine concurrent changes in pretransplant patient complexity, posttransplant survival, and cause-specific hospitalization.We identified 101 332 Medicare-insured patients who underwent their first kidney transplant in the United States between the years 1998 and 2014. We analyzed secular trends in (1) posttransplant patient and graft survival and (2) posttransplant hospitalization for cardiovascular disease, infection, and cancer using Cox models with year of kidney transplant as the primary exposure of interest.Age, dialysis vintage, body mass index, and the prevalence of a number of baseline medical comorbidities increased during the study period. Despite these adverse changes in case mix, patient survival improved: the unadjusted and multivariable-adjusted hazard ratios (HRs) for death in 2014 (versus 1998) were 0.61 (confidence interval [CI], 0.52-0.73) and 0.46 (CI, 0.39-0.55), respectively. For graft failure excluding death with a functioning graft, the unadjusted and multivariable adjusted subdistribution HRs in 2014 versus 1998 were 0.4 (CI, 0.25-0.55) and 0.45 (CI, 0.3-0.6), respectively. There was a marked decrease in hospitalizations for cardiovascular disease following transplant between 1998 and 2011, subdistribution HR 0.51 (CI, 0.43-0.6). Hospitalization for infection remained unchanged, while cancer hospitalization increased modestly.Medicare-insured patients undergoing kidney transplant became increasingly medically complex between 1998 and 2014. Despite this, both patient and graft survival improved during this period. A marked decrease in serious cardiovascular events likely contributed to this positive trend.

    View details for DOI 10.1097/TP.0000000000002670

    View details for Web of Science ID 000509347800046

    View details for PubMedID 30801531

  • Selective Serotonin Reuptake Inhibitor Use and Hip Fracture Risk Among Patients on Hemodialysis. American journal of kidney diseases : the official journal of the National Kidney Foundation Vangala, C., Niu, J., Montez-Rath, M. E., Yan, J., Navaneethan, S. D., Winkelmayer, W. C. 2019

    Abstract

    RATIONALE & OBJECTIVE: Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with hip fracture risk in the general population. This study examined this relationship among patients with kidney failure treated by hemodialysis, a unique high-risk subpopulation, within which the impact of SSRIs on hip fracture risk remains unexplored.STUDY DESIGN: Case-control study.SETTINGS & PARTICIPANTS: Eligible cases of hip fracture among maintenance hemodialysis patients between January 1, 2009, and September 30, 2015, were identified using the US Renal Data System. Each case was matched on index date with 10 eligible controls. To be eligible, study participants needed to have more than 1 year of Medicare Parts A and B coverage and more than 3 years of Part D coverage. For a separate examination of new short-term SSRI exposure, we selected cases and controls with more than 18 months of Part D coverage and no prior antidepressant use for 1 year.EXPOSURE: During the 3-year Part D coverage period, use of SSRIs characterized as any (≥1 prescription filled), low, moderate, and high use (<20%, 20%-<80%, and≥80% of days covered by filled prescriptions, respectively).OUTCOME: We selected cases using International Classification of Diseases, Ninth Revision codes 820.xx and 821.xx. In addition to 1 of these codes tied to a hospitalization, we required a corresponding surgical procedural code within 7 days of diagnosis.ANALYTIC APPROACH: Conditional logistic regression to estimate unadjusted and multivariable-adjusted ORs and 95% CIs.RESULTS: We identified 4,912 cases and 49,120 controls. SSRI use was associated with increased hip fracture risk (adjusted OR, 1.25; 95% CI, 1.17-1.35). Risk for fracture was estimated for any, low, moderate, and high SSRI use: adjusted conditional ORs were 1.25 (95% CI, 1.17-1.35), 1.20 (95% CI, 1.08-1.32), 1.31 (95% CI, 1.18-1.43), and 1.26 (95% CI, 1.12-1.41), respectively. The association between hip fracture events and SSRI use was also seen in the examination of new short-term use (adjusted OR, 1.43; 95% CI, 1.23-1.67).LIMITATIONS: Biomarkers of mineral bone disorder were not captured and accounted for in this analysis.CONCLUSIONS: We demonstrated an association between increased hip fracture risk and both long- and new short-term SSRI use. The stronger association with new short-term use may suggestan acute mechanism potentially related to falls.

    View details for DOI 10.1053/j.ajkd.2019.07.015

    View details for PubMedID 31606233

  • Cause of kidney disease and cardiovascular events in a national cohort of US patients with end- stage renal disease on dialysis: a retrospective analysis EUROPEAN HEART JOURNAL O'Shaughnessy, M. M., Liu, S., Montez-Rath, M. E., Lafayette, R. A., Winkelmayer, W. C. 2019; 40 (11): 887-+
  • Lower Extremity Amputation and Health Care Utilization in the Last Year of Life among Medicare Beneficiaries with ESRD. Journal of the American Society of Nephrology : JASN Butler, C. R., Schwarze, M. L., Katz, R., Hailpern, S. M., Kreuter, W., Hall, Y. N., Montez Rath, M. E., O'Hare, A. M. 2019

    Abstract

    BACKGROUND: Lower extremity amputation is common among patients with ESRD, and often portends a poor prognosis. However, little is known about end-of-life care among patients with ESRD who undergo amputation.METHODS: We conducted a mortality follow-back study of Medicare beneficiaries with ESRD who died in 2002 through 2014 to analyze patterns of lower extremity amputation in the last year of life compared with a parallel cohort of beneficiaries without ESRD. We also examined the relationship between amputation and end-of-life care among the patients with ESRD.RESULTS: Overall, 8% of 754,777 beneficiaries with ESRD underwent at least one lower extremity amputation in their last year of life compared with 1% of 958,412 beneficiaries without ESRD. Adjusted analyses of patients with ESRD showed that those who had undergone lower extremity amputation were substantially more likely than those who had not to have been admitted to-and to have had prolonged stays in-acute and subacute care settings during their final year of life. Amputation was also associated with a greater likelihood of dying in the hospital, dialysis discontinuation before death, and less time receiving hospice services.CONCLUSIONS: Nearly one in ten patients with ESRD undergoes lower extremity amputation in their last year of life. These patients have prolonged stays in acute and subacute health care settings and appear to have limited access to hospice services. These findings likely signal unmet palliative care needs among seriously ill patients with ESRD who undergo amputation as well as opportunities to improve their care.

    View details for PubMedID 30782596

  • Central venous pressure and the risk of diuretic-associated acute kidney injury in patients after cardiac surgery. American heart journal McCoy, I. E., Montez-Rath, M. E., Chertow, G. M., Chang, T. I. 2019; 221: 67–73

    Abstract

    When prescribing diuretics in the postcardiac surgical intensive care unit (ICU), clinicians may use central venous pressure (CVP) to assess volume status and the risk of acute kidney injury (AKI). In this study, we examined how the risk of diuretic-associated AKI varied with CVP in patients undergoing cardiac surgery.We used the Medical Information Mart for Intensive Care database to study adults admitted to the postcardiac surgical ICU at an urban, academic medical center between 2001 and 2012. We examined the odds of AKI per 1-mm Hg increase in CVP among patients receiving intravenous loop diuretics using multivariable adjusted logistic regression. We examined the risk of AKI among patients with diuretic use (vs nonuse) across tertiles of CVP using inverse probability treatment weighting.Among 4,164 patients receiving intravenous loop diuretics, the adjusted odds of subsequent AKI were 1.11 (95% CI 1.08-1.13) times higher per mm Hg increase in mean CVP. This association was log-linear across the entire range of CVPs observed. In the analysis of diuretic use (n = 5,396), the adjusted risk ratio for AKI with diuretic use (vs nonuse) was 1.33 (95% CI 1.21-1.47) and did not materially differ across tertile of CVP.Higher rather than lower CVP is an independent marker of AKI risk. The risk of AKI associated with diuretic use may not be influenced by CVP. Novel methods of assessing volume status and AKI risk are needed to guide patient selection for diuretic therapy.

    View details for DOI 10.1016/j.ahj.2019.12.013

    View details for PubMedID 31931418

  • Antidiabetic medication use in patients with type 2 diabetes and chronic kidney disease. Journal of diabetes and its complications Rhee, J. J., Han, J. n., Montez-Rath, M. E., Kim, S. H., Cullen, M. R., Stafford, R. S., Winkelmayer, W. C., Chertow, G. M. 2019: 107423

    Abstract

    To quantify patterns of conventional and newer antidiabetic medication use in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).We used data from a large claims and integrated dataset that includes employed and commercially insured patients in the US to select patients who had T2DM and CKD with information on laboratory values and prescriptions for antidiabetic medications from January 1, 2014 to January 1, 2015. We stratified the analyses by sociodemographic variables.In a cohort of 38,577 patients with T2DM and CKD, we found wide variation in the treatment of T2DM by CKD stage as well as by several sociodemographic factors. Although metformin was the most commonly prescribed medication, only about half of patients in the cohort and fewer than two-thirds of patients with early stage CKD were prescribed metformin. Approximately 10.6% of patients with CKD stage 4 and 2.1% of the patients with CKD stage 5 were prescribed metformin. Sulfonylureas with active metabolites that accumulate with impaired kidney function were prescribed in more than one-third of patients with CKD stages 3b, 4, and 5. Only 3.4% and 12.3% of patients were prescribed GLP-1 and DPP-4 respectively.Prescriptions for metformin were lower than expected among patients with mild to moderate CKD. Prescriptions for newer antidiabetic medications with known safety and efficacy across the spectrum of CKD remained low. Prescriptions for agents contraindicated in advanced CKD continued to be written in a sizeable fraction of patients.

    View details for DOI 10.1016/j.jdiacomp.2019.107423

    View details for PubMedID 31537413

  • Estimated effects of early diuretic use in critical illness. Critical care explorations McCoy, I. E., Montez-Rath, M. E., Chertow, G. M., Chang, T. I. 2019; 1 (7)

    Abstract

    To estimate the effects of diuretic use during the first 24 hours of an intensive care unit stay on in-hospital mortality and other clinical outcomes including acute kidney injury and duration of mechanical ventilation.Retrospective cohort study.Urban, academic medical center.Adult patients admitted to medical or cardiac ICUs between 2001 and 2012, excluding those on maintenance dialysis or with ICU length of stay < 24 hours.None.We included 13,589 patients: 2,606 with and 10,983 without early diuretic use (loop diuretic exposure during the first 24 hours of an ICU stay). Propensity score matching generated 2523 pairs with well-balanced baseline characteristics. Early diuretic use was unassociated with in-hospital mortality (risk ratio 1.01, 99.5% confidence interval 0.83-1.22). We found no evidence of associations with ICU or hospital length of stay, or duration or provision of mechanical ventilation. Early diuretic use was associated with higher rates of subsequent acute kidney injury (risk ratio 1.41, 99.5% confidence interval 1.25 to 1.59) and electrolyte abnormalities. Results were not materially different in subgroups of patients with heart failure, chronic kidney disease, or acute lung injury.Early diuretic use in critical illness was unassociated with in-hospital mortality, ICU or hospital length of stay, or duration of mechanical ventilation, but risks of acute kidney injury and electrolyte abnormalities were higher.

    View details for DOI 10.1097/CCE.0000000000000021

    View details for PubMedID 31440746

    View details for PubMedCentralID PMC6705600

  • Early detection of chronic kidney disease in low-income and middle-income countries: development and validation of a point-of-care screening strategy for India. BMJ global health Bradshaw, C., Kondal, D., Montez-Rath, M. E., Han, J., Zheng, Y., Shivashankar, R., Gupta, R., Srinivasapura Venkateshmurthy, N., Jarhyan, P., Mohan, S., Mohan, V., Ali, M. K., Patel, S., Venkat Narayan, K. M., Tandon, N., Prabhakaran, D., Anand, S. 2019; 4 (5): e001644

    Abstract

    Introduction: Although deaths due to chronic kidney disease (CKD) have doubled over the past two decades, few data exist to inform screening strategies for early detection of CKD in low-income and middle-income countries.Methods: Using data from three population-based surveys in India, we developed a prediction model to identify a target population that could benefit from further CKD testing, after an initial screening implemented during home health visits. Using data from one urban survey (n=8698), we applied stepwise logistic regression to test three models: one comprised of demographics, self-reported medical history, anthropometry and point-of-care (urine dipstick or capillary glucose) tests; one with demographics and self-reported medical history and one with anthropometry and point-of-care tests. The 'gold-standard' definition of CKD was an estimated glomerular filtration rate <60mL/min/1.73m2 or urine albumin-to-creatinine ratio ≥30mg/g. Models were internally validated via bootstrap. The most parsimonious model with comparable performance was externally validated on distinct urban (n=5365) and rural (n=6173) Indian cohorts.Results: A model with age, sex, waist circumference, body mass index and urine dipstick had a c-statistic of 0.76 (95% CI 0.75 to 0.78) for predicting need for further CKD testing, with external validation c-statistics of 0.74 and 0.70 in the urban and rural cohorts, respectively. At a probability cut-point of 0.09, sensitivity was 71% (95% CI 68% to 74%) and specificity was 70% (95% CI 69% to 71%). The model captured 71% of persons with CKD and 90% of persons at highest risk of complications from untreated CKD (ie, CKD stage 3A2 and above).Conclusion: A point-of-care CKD screening strategy using three simple measures can accurately identify high-risk persons who require confirmatory kidney function testing.

    View details for DOI 10.1136/bmjgh-2019-001644

    View details for PubMedID 31544000

  • Association Between Type of Vascular Access Used in Hemodialysis Patients and Subsequent Kidney Transplant Outcomes. Kidney medicine Airy, M. n., Lenihan, C. R., Ding, V. Y., Montez-Rath, M. E., Cheng, J. n., Navaneethan, S. D., Wasse, H. n., Winkelmayer, W. C. 2019; 1 (6): 383–90

    Abstract

    Vascular access type (arteriovenous fistula [AVF] vs arteriovenous graft [AVG] vs central venous catheter [CVC]) associates with clinical outcomes in patients with end-stage kidney disease undergoing hemodialysis. Whether a similar association exists with outcomes after kidney transplantation is unknown. We hypothesized that AVGs would associate with worse outcomes, perhaps owing to persistent subclinical inflammation.Retrospective cohort study.Using US registry data merged with electronic health records of a large dialysis organization (2006-2011), we selected patients receiving a first-ever kidney transplant after undergoing more than 30 days of hemodialysis.Hemodialysis access used during the patient's last pretransplantation hemodialysis session.Patients were followed up from kidney transplantation for all-cause mortality, kidney allograft loss from any cause, and allograft loss not from death.Time-to-event analysis including Kaplan-Meier plots and Cox proportional hazards regression estimated cause-specific HRs and 95% CIs.Among 9,291 patients who underwent kidney transplantation between 2006 and 2011, a total of 65.3% used an AVF, 20.4% used an AVG, and 14.3% used a CVC for hemodialysis before transplantation. Multivariable regression models adjusted for demographic variables, comorbid conditions, transplant characteristics, and laboratory parameters identified no independent associations between vascular access type and all-cause mortality (HRAVG, 1.13 [95% CI, 0.97-1.33]; HRCVC, 1.00 [95% CI, 0.83-1.21]). Similarly, AVG and CVC use were not independently associated with all-cause allograft loss compared with AVF use (HRAVG, 1.13 [95% CI, 1.00-1.28]; HRCVC, 1.12 [95% CI, 0.96-1.29]). CVC use was associated with 30% higher risk for allograft loss from causes other than death compared with AVF use (HRCVC, 1.30 [95% CI, 1.06-1.57]), but AVGs were not (HRAVG, 1.17 [95% CI, 0.98-1.39]).Nonrandomized exposure leading to potential residual confounding.No association was found for AVG use before kidney transplantation with mortality, all-cause allograft loss, and allograft loss from all causes other than death, compared with AVF use. The association of CVC use with allograft loss from causes other than death requires further investigation.

    View details for DOI 10.1016/j.xkme.2019.08.005

    View details for PubMedID 32734218

    View details for PubMedCentralID PMC7384366

  • Sodium Excretion and Cardiovascular Outcomes in African American Patients With CKD: Findings From the African American Study of Kidney Disease and Hypertension. Kidney medicine Pearson, K. n., Anderson, C. A., Jimenez, S. n., Montez-Rath, M. E., Chang, T. I. 2019; 2 (1): 80–82

    View details for DOI 10.1016/j.xkme.2019.10.008

    View details for PubMedID 32734229

    View details for PubMedCentralID PMC7380340

  • Blood Pressure and Incident Atrial Fibrillation in Older Patients Initiating Hemodialysis. Clinical journal of the American Society of Nephrology : CJASN Chang, T. I., Liu, S. n., Airy, M. n., Niu, J. n., Turakhia, M. P., Flythe, J. E., Montez-Rath, M. E., Winkelmayer, W. C. 2019

    Abstract

    We examined the association of predialysis systolic and diastolic BP and intradialytic hypotension with incident atrial fibrillation in older patients initiating hemodialysis.We used the US Renal Data System linked to the records of a large dialysis provider to identify patients aged ≥67 years initiating hemodialysis between January 2006 and October 2011. We examined quarterly average predialysis systolic BP, diastolic BP, and proportion of sessions with intradialytic hypotension (i.e., nadir systolic BP <90 mm Hg). We applied an extended Cox model to compute adjusted hazard ratios (HRs) of each exposure with incident atrial fibrillation.Among 17,003 patients, 3785 developed atrial fibrillation. When comparing predialysis systolic BP to a fixed reference of 140 mm Hg, lower predialysis systolic BP was associated with a higher hazard of atrial fibrillation, whereas higher systolic BP was associated with a lower hazard of atrial fibrillation. When comparing across a range of systolic BP for two hypothetical patients with similar measured covariates, the association varied by mean systolic BP: at systolic BP 190 mm Hg, each 10 mm Hg lower systolic BP was associated with lower atrial fibrillation hazard (HR, 0.94; 95% confidence interval, 0.90 to 1.00), whereas at systolic BP 140 mm Hg, a 10 mm Hg lower systolic BP was associated with a higher atrial fibrillation hazard (HR, 1.12; 95% confidence interval, 1.10 to 1.14). Lower diastolic BP was associated with higher atrial fibrillation hazards. Intradialytic hypotension was weakly associated with atrial fibrillation.In this observational study of older patients initiating hemodialysis, lower predialysis systolic BP and diastolic BP were associated with higher incidence of atrial fibrillation.

    View details for DOI 10.2215/CJN.13511118

    View details for PubMedID 31175104

  • Nephrotoxin exposure and acute kidney injury in critically ill children undergoing congenital cardiac surgery PEDIATRIC NEPHROLOGY Uber, A. M., Montez-Rath, M. E., Kwiatkowski, D. M., Krawczeski, C. D., Sutherland, S. M. 2018; 33 (11): 2193–99
  • The Relationship between Intradialytic Hypotension and Hospitalized Mesenteric Ischemia: A Case-Control Study. Clinical journal of the American Society of Nephrology : CJASN Seong, E. Y., Zheng, Y., Winkelmayer, W. C., Montez-Rath, M. E., Chang, T. I. 2018

    Abstract

    BACKGROUND AND OBJECTIVES: Mesenteric ischemia is a rare but devastating condition caused by insufficient blood supply to meet the demands of intestinal metabolism. In patients with ESKD, it can be difficult to diagnose and has a >70% mortality rate. Patients on hemodialysis have a high prevalence of predisposing conditions for mesenteric ischemia, but the contribution of intradialytic hypotension, a potential modifiable risk factor, has not been well described.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used data from the US Renal Data System to identify 626 patients on hemodialysis with a hospitalized mesenteric ischemia event (cases). We selected 2428 controls in up to a 1:4 ratio matched by age, sex, black race, incident dialysis year, diabetes mellitus, coronary artery disease, and peripheral artery disease. We used six different definitions of intradialytic hypotension on the basis of prior studies, and categorized patients as having had intradialytic hypotension if ≥30% of hemodialysis sessions in the 30 days before the event met the specified definition.RESULTS: The proportion of patients with intradialytic hypotension varied depending on its definition: from 19% to 92% of cases and 11% to 94% of controls. Cases had a higher adjusted odds (1.82; 95% confidence interval, 1.47 to 2.26) of having had intradialytic hypotension in the preceding 30 days than controls when using nadir-based intradialytic hypotension definitions such as nadir systolic BP <90 mm Hg. To examine a potential dose-response association of intradialytic hypotension with hospitalized mesenteric ischemia, we categorized patients by the proportion of hemodialysis sessions having intradialytic hypotension, defined using the Nadir90 definition (0%, 1%-9%, 10%-29%, 30%-49%, and ≥50%), and found a direct association of proportion of intradialytic hypotension with hospitalized mesenteric ischemia (P-trend<0.001).CONCLUSIONS: Patients with hospitalized mesenteric ischemia had significantly higher odds of having had intradialytic hypotension in the preceding 30 days than controls, as defined by nadir-based definitions.

    View details for PubMedID 30237215

  • 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

  • Cause of kidney disease and cardiovascular events in a national cohort of US patients with end-stage renal disease on dialysis: a retrospective analysis. European heart journal O'Shaughnessy, M. M., Liu, S., Montez-Rath, M. E., Lafayette, R. A., Winkelmayer, W. C. 2018

    Abstract

    Aims: End-stage renal disease (ESRD) is a strong cardiovascular risk factor. We aimed to determine the extent to which cause of kidney disease independently contributes to this risk.Methods and results: Using a national US ESRD registry, we selected patients with eight different causes of ESRD who initiated dialysis 1997-2014. We used proportional sub-distribution hazard models, with non-cardiovascular death or kidney transplantation as competing risks, to estimate hazard ratios (HRs) for a first composite cardiovascular event (myocardial infarction, ischaemic stroke, or cardiovascular or cerebrovascular death), by cause of ESRD. The population was restricted to those using Medicare insurance at Day 91 after dialysis initiation (when most patients become Medicare eligible). Outcomes were ascertained from Medicare claims or Death Notifications. Among the 658168 patients identified, composite event rates ranged from 3.5/100 person-years in IgA nephropathy to 14.6/100 person-years in diabetic nephropathy (DN). After adjusting for demographics, socioeconomic factors, comorbidities, dialysis modality, and laboratory values, cardiovascular event HRs differed significantly by cause of ESRD. Comparing to IgA nephropathy, the adjusted HR was highest for DN [aHR=2.97, 95% confidence interval (CI) 2.77-3.20], next highest for lupus nephritis (aHR=1.86, 95% CI 1.71-2.03), and thereafter ranged from 1.29 (95% CI 1.19-1.39) in autosomal dominant polycystic kidney disease to 1.67 (95% CI 1.52-1.83) in membranous nephropathy.Conclusion: High cardiovascular event rates in dialysis patients vary considerably by cause of ESRD. Determining underlying reasons for these differences might provide new insights in to cardiovascular disease mechanisms as well as inform future drug development and clinical trial design.

    View details for PubMedID 30085056

  • Nephrotoxin exposure and acute kidney injury in critically ill children undergoing congenital cardiac surgery. Pediatric nephrology (Berlin, Germany) Uber, A. M., Montez-Rath, M. E., Kwiatkowski, D. M., Krawczeski, C. D., Sutherland, S. M. 2018

    Abstract

    BACKGROUND: Though acute kidney injury (AKI) is often multifactorial, investigators are now emphasizing the specific contribution of nephrotoxins. This study examines the epidemiology of nephrotoxin exposure and nephrotoxin-associated AKI among children undergoing congenital heart surgery (CHS).METHODS: This is a retrospective cohort study of children admitted following CHS between June 1, 2014, and September 30, 2014. Nephrotoxins were defined according to the Nephrotoxic Injury Negated by Just-in-time-Action (NINJA) collaborative; high nephrotoxin exposure was defined as receipt of ≥3 nephrotoxins concurrently. AKI was diagnosed according to KDIGO creatinine criteria. Severe AKI was defined as KDIGO stage ≥2. Poisson models were used to compute adjusted relative risk (aRR) of high nephrotoxin exposure for AKI.RESULTS: One hundred fifty-four children (median age 20.4months, IQR 2.3-59.5) were included. One hundred thirty-one (85.1%) received at least one nephrotoxin; 32 (20.8%) received ≥3 nephrotoxins. The most commonly administered medications were ketorolac (n=74, 48.1%), aspirin (n=62, 40.3%), ibuprofen (n=51, 33.1%), vancomycin (n=39, 25.3%), piperacillin/tazobactam (n=35, 22.7%), and enalapril (n=14, 9.1%). AKI occurred more commonly in those exposed to ≥3 nephrotoxins (62.5 vs. 50.8%); this was not statistically significant after adjusting for confounders (aRR=1.2, 95% CI 0.9-1.7). Severe AKI was similar between those with and without high nephrotoxin exposure (21.9 vs. 19.7%, p=0.78).CONCLUSIONS: Nephrotoxin use is common following pediatric CHS. While we found no association between high nephrotoxin exposure and AKI, this may be related to the multifactorial nature of AKI in this population. For many common nephrotoxins, less injurious agents exist and nephrotoxin exposure may represent a modifiable risk factor for AKI.

    View details for PubMedID 29987455

  • Trends in Rates of Lower Extremity Amputation Among Patients With End-stage Renal Disease Who Receive Dialysis. JAMA internal medicine Franz, D., Zheng, Y., Leeper, N. J., Chandra, V., Montez-Rath, M., Chang, T. I. 2018

    Abstract

    Patients with end-stage renal disease (ESRD) who receive dialysis are at high risk of lower extremity amputation. Recent studies indicate decreasing rates of lower extremity amputation in non-ESRD populations, but contemporary data for patients with ESRD who receive dialysis are lacking.To assess rates of lower extremity amputation among patients with ESRD who receive dialysis during a recent 15-year period; to analyze whether those rates differed by age, sex, diabetes, or geographic region; and to determine 1-year mortality rates in this population after lower extremity amputation.This retrospective study of 3 700 902 records obtained from a US national registry of patients with ESRD who receive dialysis assessed cross-sectional cohorts for each calendar year from 2000 through 2014. Adult patients with prevalent ESRD treated with hemodialysis or peritoneal dialysis covered by Medicare Part A and B on January 1 of each cohort year were included. Data analysis was conducted from August 2017 to April 2018.Age, sex, diabetes, and hospital referral region.Annual rates per 100 person-years of nontraumatic major (above- or below-knee) and minor (below-ankle) amputations.For each annual cohort, there were fewer women (47.5% in 2000, 46.2% in 2005, 44.9% in 2010, and 44.0% in 2014) than men, more than half the patients were white individuals (58.1% in 2000, 56.9% in 2005, 56.9% in 2010, and 56.7% in 2014), and a small proportion were employed (13.9% in 2000, 15.1% in 2005, 16.1% in 2010, and 16.5% in 2014). The rate of lower extremity amputations for patients with ESRD who receive dialysis decreased by 51.0% from 2000 to 2014, driven primarily by a decrease in the rate of major amputations (5.42 [95% CI, 5.28-5.56] in 2000 vs 2.66 [95% CI, 2.59-2.72] per 100 person-years in 2014). Patients with diabetes had amputation rates more than 5 times as high as patients without diabetes. Patients younger than 65 years had higher adjusted amputation rates than older patients, and men had consistently higher adjusted amputation rates than women. Adjusted 1-year mortality rates after lower extremity amputation for patients with ESRD who receive dialysis decreased from 52.2% (95% CI, 50.9%-53.4%) in 2000 to 43.6% (95% CI, 42.5%-44.8%) in 2013. In general, amputation rates decreased among all regions from 2000 to 2014, but regional variability persisted across time despite adjustment for differences in patient demographics and comorbid conditions.Although rates of lower extremity amputations among US patients with ESRD who receive dialysis decreased by 51% during a recent 15-year period, mortality rates remained high, with nearly half of patients dying within a year after lower extremity amputation. Our results highlight the need for more research on ways to prevent lower extremity amputation in this extremely high-risk population.

    View details for DOI 10.1001/jamainternmed.2018.2436

    View details for PubMedID 29987332

  • 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
  • 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

  • Trends in Rates of Lower Extremity Amputation Among Patients With End-Stage Renal Disease Who Receive Dialysis JAMA Internal Medicine Franz, D., Zheng, Y., Leeper, N. J., Chandra, V., Montez-Rath, M., Chang, T. I. 2018
  • 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

  • Do attributes of persons with chronic kidney disease differ in low-income and middle-income countries compared with high-income countries? Evidence from population-based data in six countries BMJ GLOBAL HEALTH Anand, S., Zheng, Y., Montez-Rath, M. E., Wei, W., Perico, N., Carminati, S., Narayan, K., Tandon, N., Mohan, V., Jha, V., Zhang, L., Remuzzi, G., Prabahkaran, D., Chertow, G. M. 2017; 2 (4): e000453

    Abstract

    Kidney biopsies to elucidate the cause of chronic kidney disease (CKD) are performed in a minority of persons with CKD living in high-income countries, since associated conditions-that is, diabetes mellitus, vascular disease or obesity with pre-diabetes, prehypertension or dyslipidaemia-can inform management targeted at slowing CKD progression in a majority. However, attributes of CKD may differ substantially among persons living in low-income and middle-income countries (LMICs). We used data from population or community-based studies from five LMICs (China, urban India, Moldova, Nepal and Nigeria) to determine what proportion of persons with CKD living in diverse regions fit one of the three major clinical profiles, with data from the US National Health Nutrition and Examination Survey as reference. In the USA, urban India and Moldova, 79.0%-83.9%; in China and Nepal, 62.4%-66.7% and in Nigeria, 51.6% persons with CKD fit one of three established risk profiles. Diabetes was most common in urban India and vascular disease in Moldova (50.7% and 33.2% of persons with CKD in urban India and Moldova, respectively). In Nigeria, 17.8% of persons with CKD without established risk factors had albuminuria ≥300 mg/g, the highest proportion in any country. While the majority of persons with CKD in LMICs fit into one of three established risk profiles, the proportion of persons who have CKD without established risk factors is higher than in the USA. These findings can inform tailored CKD detection and management systems and highlight the importance of studying potential causes and outcomes of CKD without established risk factors in LMICs.

    View details for PubMedID 29071132

  • Declining Rates of Hip Fracture in End-Stage Renal Disease: Analysis From the 2003-2011 Nationwide Inpatient Sample JOURNAL OF BONE AND MINERAL RESEARCH Kim, S., Liu, S., Long, J., Montez-Rath, M. E., Leonard, M. B., Chertow, G. M. 2017; 32 (11): 2297–2303

    Abstract

    The incidence of hip fracture in patients with end-stage renal disease (ESRD) is considerably higher than that in the general age- and sex-matched population. Although medical therapy for chronic kidney disease mineral bone disorder (CKD-MBD) has changed considerably over the last decade, rates of hip fracture in the entire ESRD population have not been well-characterized. Herein, we evaluated temporal trends in rates of hip fracture, in-hospital mortality, and costs of associated hospital stay in ESRD. We identified hospitalizations for hip fracture from 2003 to 2011 using the Nationwide Inpatient Sample, a representative national database inclusive of all ages and payers. We incorporated data from the United States Renal Data System and the US Census to calculate population-specific rates. Between 2003 and 2011, we identified 47,510 hip fractures in the ESRD population. The overall rate of hip fracture was 10.04/1000 person-years. The rate was 3.73/1000 person-years in patients aged less than 65 years, and 20.97/1000 person-years in patients aged 65 or older. Age- and sex-standardized rates decreased by 12.6% from 2003 (10.23/1000 person-years; 95% confidence interval [CI], 7.99/1000 to 12.47/1000) to 2011 (8.94/1000 person-years; 95% CI, 7.12/1000 to 10.75/1000). Hip fracture rates over time were virtually identical in patients aged less than 65 years; however, rates decreased by 15.3% among patients aged 65 years or older; rates declined more rapidly in older women compared with older men (p for interaction = 0.047). In-hospital mortality rate after hip fracture operation declined by 26.7% from 2003 (8.6%; 95% CI, 6.8 to 10.4) to 2011 (6.3%; 95% CI, 4.9 to 7.7). In ESRD, age- and sex-standardized hip fracture rates and associated in-hospital mortality have declined substantially over the last decade. © 2017 American Society for Bone and Mineral Research.

    View details for PubMedID 28639740

  • Associations of Glycemic Control With Cardiovascular Outcomes Among US Hemodialysis Patients With Diabetes Mellitus. Journal of the American Heart Association Rhee, J. J., Zheng, Y., Montez-Rath, M. E., Chang, T. I., Winkelmayer, W. C. 2017; 6 (6)

    Abstract

    There is a lack of data on the relationship between glycemic control and cardiovascular end points in hemodialysis patients with diabetes mellitus.We included adult Medicare-insured patients with diabetes mellitus who initiated in-center hemodialysis treatment from 2006 to 2008 and survived for >90 days. Quarterly mean time-averaged glycated hemoglobin (HbA1c) values were categorized into <48 mmol/mol (<6.5%) (reference), 48 to <58 mmol/mol (6.5% to <7.5%), 58 to <69 mmol/mol (7.5% to <8.5%), and ≥69 mmol/mol (≥8.5%). Medicare claims were used to identify outcomes of cardiovascular mortality, nonfatal myocardial infarction (MI), fatal or nonfatal MI, stroke, and peripheral arterial disease. We used Cox models as a function of time-varying exposure to estimate multivariable adjusted hazard ratios and 95%CI for the associations between HbA1c and time to study outcomes in a cohort of 16 387 eligible patients. Patients with HbA1c 58 to <69 mmol/mol (7.5% to <8.5%) and ≥69 mmol/mol (≥8.5%) had 16% (CI, 2%, 32%) and 18% (CI, 1%, 37%) higher rates of cardiovascular mortality (P-trend=0.01) and 16% (CI, 1%, 33%) and 15% (CI, 1%, 32%) higher rates of nonfatal MI (P-trend=0.05), respectively, compared with those in the reference group. Patients with HbA1c ≥69 mmol/mol (≥8.5%) had a 20% (CI, 2%, 41%) higher rate of fatal or nonfatal MI (P-trend=0.02), compared with those in the reference group. HbA1c was not associated with stroke, peripheral arterial disease, or all-cause mortality.Higher HbA1c levels were significantly associated with higher rates of cardiovascular mortality and MI but not with stroke, peripheral arterial disease, or all-cause mortality in this large cohort of hemodialysis patients with diabetes mellitus.

    View details for DOI 10.1161/JAHA.117.005581

    View details for PubMedID 28592463

  • 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

  • Statin use and hip fractures in US kidney transplant recipients BMC NEPHROLOGY Vangala, C., Lenihan, C. R., Montez-Rath, M. E., Nair, S. S., Navaneethan, S. D., Ramanathan, V., Winkelmayer, W. C. 2017; 18

    Abstract

    Basic and translational research supports beneficial effects of statins on bone metabolism. Clinical studies suggest that statin use may reduce the risk of hip fractures in the general population. Whether statin use is associated with hip fracture risk in kidney transplant recipients, a particularly high-risk group for this outcome, is unknown.From the U.S. Renal Data System (2007-2011), we identified all hip fracture events recorded in Medicare billing claims of first-time kidney transplant recipients. We then matched all cases to an unlimited number of controls on age (±3 years), sex, race (black vs. non-black), and time since transplant. Cases and controls were required to have >1 year of Medicare Parts A + B + D coverage and be without a recorded history of hip fracture. We ascertained any statin use in the previous year and defined adherent statin use as those who had filled prescriptions for statins to cover >80% of days in that year (proportion of days covered, PDC). We ascertained several potential confounders (demographics, comorbidities, BMI, transplant-related factors) and applied conditional logistic regression with multiple imputation for missing data to estimate odds ratios (OR) and 95% confidence intervals (CI).We identified 231 hip fracture cases (mean age 51.8 years; 53% female; 11.3% black; 6.9 years from transplant, and 9.9 years from ESRD) and 15,575 matched controls. Any prior statin use was present in 64.1% of cases and 60.3% of controls with 37.2% of cases and 33.9% of controls being found adherent. Unadjusted conditional logistic regression showed an OR of 1.17 (0.89-1.54) for any statin use, and a fully-adjusted OR of 0.89 (0.67-1.19). Compared with statin non-users, the adjusted OR for patients with lesser adherence (PDC ≤80%) and those with greater adherence (PDC >80%) were 0.93 (0.66-1.31) and 0.87 (0.63-1.20), respectively.Statin use was not associated with hip fracture risk in first-time kidney transplant recipients.

    View details for DOI 10.1186/s12882-017-0559-9

    View details for Web of Science ID 000400586100004

    View details for PubMedID 28460645

  • Proton Pump Inhibitor Use and Risk of Hip Fracture in Kidney Transplant Recipients AMERICAN JOURNAL OF KIDNEY DISEASES Lenihan, C. R., Nair, S. S., Vangala, C., Ramanathan, V., Montez-Rath, M. E., Winkelmayer, W. C. 2017; 69 (5): 595-601
  • Drug-Eluting Stents Versus Bare Metal Stents for Percutaneous Coronary Intervention in Kidney Transplant Recipients. Transplantation Lenihan, C. R., Montez-Rath, M. E., Winkelmayer, W. C., Chang, T. I. 2017; 101 (4): 851-857

    Abstract

    The comparative effectiveness of percutaneous coronary intervention (PCI) with drug-eluting stents (DES) versus bare metal stents (BMS) has not been studied in the kidney transplant population.Using the US Renal Data System, we identified 3245 kidney transplant patients who underwent PCI between April 2003 and December 2010; 2400 and 845 patients received DES and BMS, respectively. We used propensity score matching and inverse probability of treatment weighting to create DES- and BMS-treated groups whose observed baseline characteristics were well-balanced. The associations between stent type and the outcomes of (1) death; (2) death or myocardial infarction (MI); (3) death, MI, or repeat revascularization (RR); and (4) hospitalized bleeding were compared using Cox proportional hazards regression.Drug-eluting stent use increased during the study period, mirroring the trend described in the general population. In the propensity score-matched cohort, no significant association among DES (vs BMS) use and outcomes was observed at 1 and 2 years of follow-up. However, at 3 years, DES was associated with 20% (95% confidence interval [CI], 4-33%) lower risk of death, 15% (95% CI, 1-27%) lower risk of death or MI, and 14% (95% CI, 2-24%) lower risk of death, MI, or repeat revascularization. There were no significant differences in rates of hospitalized bleeding at any time point. Results were similar in the inverse probability of treatment weighting analysis.In this retrospective study of US kidney transplant recipients undergoing PCI, DES was associated with better clinical outcomes beyond 2 years of follow-up.

    View details for DOI 10.1097/TP.0000000000001446

    View details for PubMedID 27517730

  • Cardiac Predictors of Renal Recovery After Pediatric Left Ventricular Assist Device (LVAD) Implantation Chen, C., Montez-Rath, M. E., May, L. J., Maeda, K., Hollander, S. A., Rosenthal, D. N., Sutherland, S. M., Krawczeski, C. D. ELSEVIER SCIENCE INC. 2017: S281–S282
  • Drug-Eluting Stents Versus Bare Metal Stents for Percutaneous Coronary Intervention in Kidney Transplant Recipients TRANSPLANTATION Lenihan, C. R., Montez-Rath, M. E., Winkelmayer, W. C., Chang, T. I. 2017; 101 (4): 851-857
  • Comparative effectiveness of angiotensin receptor blockers vs. angiotensin-converting enzyme inhibitors on cardiovascular outcomes in patients initiating peritoneal dialysis JOURNAL OF NEPHROLOGY Shen, J. I., Saxena, A. B., Montez-Rath, M. E., Leng, L., Chang, T. I., Winkelmayer, W. C. 2017; 30 (2): 281-288
  • Prevalence of chronic kidney disease and risk factors for its progression: A cross-sectional comparison of Indians living in Indian versus US cities PLOS ONE Anand, S., Kondal, D., Montez-Rath, M., Zheng, Y., Shivashankar, R., Singh, K., Gupta, P., Gupta, R., Ajay, V. S., Mohan, V., Pradeepa, R., Tandon, N., Ali, M. K., Narayan, K. M., Chertow, G. M., Kandula, N., Prabhakaran, D., Kanaya, A. M. 2017; 12 (3)

    Abstract

    While data from the latter part of the twentieth century consistently showed that immigrants to high-income countries faced higher cardio-metabolic risk than their counterparts in low- and middle-income countries, urbanization and associated lifestyle changes may be changing these patterns, even for conditions considered to be advanced manifestations of cardio-metabolic disease (e.g., chronic kidney disease [CKD]).Using cross-sectional data from the Center for cArdiometabolic Risk Reduction in South Asia (CARRS, n = 5294) and Mediators of Atherosclerosis in South Asians Living in America (MASALA, n = 748) studies, we investigated whether prevalence of CKD is similar among Indians living in Indian and U.S. cities. We compared crude, age-, waist-to-height ratio-, and diabetes- adjusted CKD prevalence difference. Among participants identified to have CKD, we compared management of risk factors for its progression. Overall age-adjusted prevalence of CKD was similar in MASALA (14.0% [95% CI 11.8-16.3]) compared with CARRS (10.8% [95% CI 10.0-11.6]). Among men the prevalence difference was low (prevalence difference 1.8 [95% CI -1.6,5.3]) and remained low after adjustment for age, waist-to-height ratio, and diabetes status (-0.4 [-3.2,2.5]). Adjusted prevalence difference was higher among women (prevalence difference 8.9 [4.8,12.9]), but driven entirely by a higher prevalence of albuminuria among women in MASALA. Severity of CKD--i.e., degree of albuminuria and proportion of participants with reduced glomerular filtration fraction--was higher in CARRS for both men and women. Fewer participants with CKD in CARRS were effectively treated. 4% of CARRS versus 51% of MASALA participants with CKD had A1c < 7%; and 7% of CARRS versus 59% of MASALA participants blood pressure < 140/90 mmHg. Our analysis applies only to urban populations. Demographic--particularly educational attainment--differences among participants in the two studies are a potential source of bias.Prevalence of CKD among Indians living in Indian and U.S. cities is similar. Persons with CKD living in Indian cities face higher likelihood of experiencing end-stage renal disease since they have more severe kidney disease and little evidence of risk factor management.

    View details for DOI 10.1371/journal.pone.0173554

    View details for PubMedID 28296920

  • 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

  • Validating identification of patients with small vessel vasculitis, with or without renal involvement, using administrative healthcare records. Clinical nephrology O'Shaughnessy, M. M., Cheng, X. S., Montez-Rath, M. E., Lafayette, R. A., Winkelmayer, W. C. 2017; 87 (2017) (3): 159-162

    View details for DOI 10.5414/CN109035

    View details for PubMedID 28102817

  • Kidney Transplantation Rates Across Glomerulonephritis Subtypes in the United States. Transplantation O'Shaughnessy, M. M., Liu, S., Montez-Rath, M. E., Lafayette, R. A., Winkelmayer, W. C. 2017

    Abstract

    Whether kidney transplantation rates differ by glomerulonephritis (GN) subtype remains largely unknown.Using the US Renal Data System, we identified all adult patients with ESRD attributed to 1 of 6 GN subtypes who initiated dialysis in the US (1996-2013). Patients with diabetic nephropathy (DN) and autosomal-dominant polycystic kidney disease (ADPKD) served as "external" non-GN comparators. Using Cox proportional hazards regression, with death considered a competing risk, we estimated hazard ratios [HRs (95% confidence intervals)] for first kidney transplantation, controlling for year, demographics, comorbidities, socioeconomic factors, and Organ Procurement Organization (OPO).Among 718,480 patients studied, unadjusted and multivariable-adjusted transplant rates differed considerably across GN subtypes. Adjusted transplant rates were highest for patients with IgA nephropathy (IgAN, referent) and lower for all other groups: focal segmental glomerulosclerosis, HR=0.80 (0.77-0.82); membranous nephropathy, HR=0.88 (0.83-0.93); membranoproliferative GN, HR=0.84 (0.76-0.92); lupus nephritis, HR=0.69 (0.66-0.71); vasculitis, HR=0.66 (0.61-0.70); DN, HR=0.50 (0.47-0.52); ADPKD, HR=0.85 (0.82-0.88). Reduced kidney transplantation rates among comparator groups were driven more so by lower rates of waitlisting [HRs, vs. IgAN, ranged from 0.49 for DN to 0.92 for membranous nephropathy or ADPKD] than by lower rates of deceased donor kidney transplantation after waitlisting [rates were only significantly lower, vs. IgAN, for those with secondary GN subtypes: lupus nephritis, HR=0.91 (0.86-0.97), vasculitis, HR=0.85 (0.76-0.94); DN, HR=0.73 (0.69-0.77)].Identifying underlying reasons for apparent disease-specific barriers to kidney transplantation might inform center-specific transplant candidate selection procedures, along with national organ allocation policies, leading to more equitable patient care and improved patient outcomes.

    View details for DOI 10.1097/TP.0000000000001657

    View details for PubMedID 28207635

  • Kidney Transplantation Outcomes across GN Subtypes in the United States JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY O'Shaughnessy, M. M., Liu, S., Montez-Rath, M. E., Lenihan, C. R., Lafayette, R. A., Winkelmayer, W. C. 2017; 28 (2): 632-644

    Abstract

    Differences in kidney transplantation outcomes across GN subtypes have rarely been studied. From the US Renal Data System, we identified all adult (≥18 years) first kidney transplant recipients (1996-2011) with ESRD attributed to one of six GN subtypes or two comparator kidney diseases. We computed hazard ratios (HRs) for death, all-cause allograft failure, and allograft failure excluding death as a cause (competing risks framework) using Cox proportional hazards regression. Among the 32,131 patients with GN studied, patients with IgA nephropathy (IgAN) had the lowest mortality rates and patients with IgAN or vasculitis had the lowest allograft failure rates. After adjusting for patient- and transplant-related factors, compared with IgAN (referent), FSGS, membranous nephropathy, membranoproliferative GN, lupus nephritis, and vasculitis associated with HRs (95% confidence intervals) for death of 1.57 (1.43 to 1.72), 1.52 (1.34 to 1.72), 1.76 (1.55 to 2.01), 1.82 (1.63 to 2.02), and 1.56 (1.34 to 1.81), respectively, and with HRs for allograft failure excluding death as a cause of 1.20 (1.12 to 1.28), 1.27 (1.14 to 1.41), 1.50 (1.36 to 1.66), 1.11 (1.02 to 1.20), and 0.94 (0.81 to 1.09), respectively. Considering external comparator groups, and comparing with IgAN, autosomal dominant polycystic kidney disease (ADPKD) and diabetic nephropathy associated with higher HRs for mortality [1.22 (1.12 to 1.34) and 2.57 (2.35 to 2.82), respectively], but ADPKD associated with a lower HR for allograft failure excluding death as a cause [0.85 (0.79 to 0.91)]. Reasons for differential outcomes by GN subtype and cause of ESRD should be examined in future research.

    View details for DOI 10.1681/ASN.2016020126

    View details for Web of Science ID 000393017600025

    View details for PubMedID 27432742

  • Estimating the Risk of Radiocontrast-Associated Nephropathy JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Wilhelm-Leen, E., Montez-Rath, M. E., Chertow, G. 2017; 28 (2): 653-659

    Abstract

    Estimates of the incidence of radiocontrast-associated nephropathy vary widely and suffer from misclassification of the cause of AKI and confounding. Using the Nationwide Inpatient Sample, we created multiple estimates of the risk of radiocontrast-associated nephropathy among adult patients hospitalized in the United States in 2009. First, we stratified patients according to the presence or absence of 12 relatively common diagnoses associated with AKI and evaluated the rate of AKI between strata. Next, we created a logistic regression model, controlling for comorbidity and acuity of illness, to estimate the risk of AKI associated with radiocontrast administration within each stratum. Finally, we performed an analysis stratified by the degree of preexisting comorbidity. In general, patients who received radiocontrast did not develop AKI at a clinically significant higher rate. Adjusted only for the complex survey design, patients to whom radiocontrast was and was not administered developed AKI at rates of 5.5% and 5.6%, respectively. After controlling for comorbidity and acuity of illness, radiocontrast administration associated with an odds ratio for AKI of 0.93 (95% confidence interval, 0.88 to 0.97). In conclusion, the risk of radiocontrast-associated nephropathy may be overstated in the literature and overestimated by clinicians. More accurate AKI risk estimates may improve clinical decision-making when attempting to balance the potential benefits of radiocontrast-enhanced imaging and the risk of AKI.

    View details for DOI 10.1681/ASN.2016010021

    View details for PubMedID 27688297

  • Predicting mortality over different time horizons: which data elements are needed? Journal of the American Medical Informatics Association Goldstein, B. A., Pencina, M. J., Montez-Rath, M. E., Winkelmayer, W. C. 2017; 24 (1): 176-181

    Abstract

    Electronic health records (EHRs) are a resource for "big data" analytics, containing a variety of data elements. We investigate how different categories of information contribute to prediction of mortality over different time horizons among patients undergoing hemodialysis treatment.We derived prediction models for mortality over 7 time horizons using EHR data on older patients from a national chain of dialysis clinics linked with administrative data using LASSO (least absolute shrinkage and selection operator) regression. We assessed how different categories of information relate to risk assessment and compared discrete models to time-to-event models.The best predictors used all the available data (c-statistic ranged from 0.72-0.76), with stronger models in the near term. While different variable groups showed different utility, exclusion of any particular group did not lead to a meaningfully different risk assessment. Discrete time models performed better than time-to-event models.Different variable groups were predictive over different time horizons, with vital signs most predictive for near-term mortality and demographic and comorbidities more important in long-term mortality.

    View details for DOI 10.1093/jamia/ocw057

    View details for PubMedID 27357832

    View details for PubMedCentralID PMC5201182

  • 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

  • Proton Pump Inhibitor Use and Risk of Hip Fracture in Kidney Transplant Recipients. American journal of kidney diseases Lenihan, C. R., Nair, S. S., Vangala, C., Ramanathan, V., Montez-Rath, M. E., Winkelmayer, W. C. 2016

    Abstract

    Posttransplantation bone disease is a significant problem, with few well-evidenced therapeutic options. Proton pump inhibitors (PPIs) are associated with hip fracture in the general population and are widely prescribed for kidney transplant recipients.A case-control study.From the US Renal Data System, we identified from diagnoses and procedures 231 kidney transplant recipients with a first hip fracture. Cases were matched at the hip fracture index date with 15,575 controls on age, sex, race, and transplantation year.PPI use.First hip fracture.In the year prior to the index date, a PPI was prescribed to 65.4% of cases and 57.4% of controls. Additionally, in 34.6% of cases and 28.9% of controls, a PPI was prescribed for >80% of the year preceding the index date (higher PPI users). Unadjusted ORs of hip fracture associated with any and higher PPI use were 1.55 (95% CI, 1.18-2.05) and 1.65 (95% CI, 1.2-2.27), respectively. When adjusted for baseline demographic, clinical, and pharmacologic covariables, any and higher PPI use remained associated with hip fracture, with ORs of 1.39 (95% CI, 1.04-1.84) and 1.41 (95% CI, 1.02-1.95), respectively.Potential residual confounding through either incorrectly ascertained or unavailable confounders; cohort limited to Medicare beneficiaries receiving low-income subsidy.In summary, PPI use was associated with hip fracture risk in the US kidney transplant population.

    View details for DOI 10.1053/j.ajkd.2016.09.019

    View details for PubMedID 27866965

  • 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

  • Hip Fracture in Patients With Non-Dialysis-Requiring Chronic Kidney Disease. Journal of bone and mineral research Kim, S. M., Long, J., Montez-Rath, M., Leonard, M., Chertow, G. M. 2016; 31 (10): 1803-1809

    Abstract

    Patients with end-stage renal disease (ESRD) are at a high risk for hip fracture. Little is known about the risk for, and consequences of, hip fracture among patients with non-dialysis-requiring chronic kidney disease (CKD). We examined the incidence of hip fracture, in-hospital mortality, length of stay, and costs among patients with ESRD, non-dialysis-requiring CKD, and normal or near normal kidney function. Using the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, a nationally representative database, we identified hospitalizations for hip fracture in 2010. We incorporated data from the United States Renal Data System (USRDS) and the US census to calculate population-specific rates. Age-standardized incidence of hip fracture was highest among patients with ESRD (3.89/1000 person-years), followed by non-dialysis-requiring CKD (1.81/1000 persons) and patients with normal or near normal kidney function (1.18/1000 persons). In-hospital mo rtality (odds ratio [OR] = 1.69, 95% confidence interval [CI] 1.46 to 1.96), lengths of stay (median [10th, 90th percentiles] 5 [3 to 11] versus 5 [3 to 10] days) and costs (median $14,807 versus $13,314) were significantly higher in patients with non-dialysis-requiring CKD relative to patients with normal or near normal kidney function. In summary, non-dialysis-requiring CKD is associated with higher age-standardized rates of hip fracture and post-hip fracture mortality and higher resource utilization. © 2016 American Society for Bone and Mineral Research.

    View details for DOI 10.1002/jbmr.2862

    View details for PubMedID 27145189

  • Multivariate Risk Adjustment of Primary Care Patient Panels in a Public Health Setting: A Comparison of Statistical Models. The Journal of ambulatory care management Hirozawa, A. M., Montez-Rath, M. E., Johnson, E. C., Solnit, S. A., Drennan, M. J., Katz, M. H., Marx, R. 2016; 39 (4): 333-342

    Abstract

    We compared prospective risk adjustment models for adjusting patient panels at the San Francisco Department of Public Health. We used 4 statistical models (linear regression, two-part model, zero-inflated Poisson, and zero-inflated negative binomial) and 4 subsets of predictor variables (age/gender categories, chronic diagnoses, homelessness, and a loss to follow-up indicator) to predict primary care visit frequency. Predicted visit frequency was then used to calculate patient weights and adjusted panel sizes. The two-part model using all predictor variables performed best (R = 0.20). This model, designed specifically for safety net patients, may prove useful for panel adjustment in other public health settings.

    View details for DOI 10.1097/JAC.0000000000000065

    View details for PubMedID 27576054

  • 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

  • Antihypertensive Medication Use in Older Patients Transitioning from Chronic Kidney Disease to End-Stage Renal Disease on Dialysis. Clinical journal of the American Society of Nephrology Chang, T. I., Zheng, Y., Montez-Rath, M. E., Winkelmayer, W. C. 2016; 11 (8): 1401-1412

    Abstract

    The transition from CKD to ESRD can be particularly unstable, with high rates of death and hospitalizations. Few studies have examined medication use during this critical period. We examined patterns of antihypertensive medication use from the four quarters before and eight quarters after incident ESRD treated with maintenance dialysis.We used the US Renal Data System to identify patients aged ≥67 years initiating dialysis for ESRD between January 2008 and December 2010 with Medicare Part D and a low-income subsidy. We ascertained the incidence of AKI and hyperkalemia during each quarter on the basis of having at least 1 payment claim for the condition. We used Poisson regression with robust SEMs to formally test for changes in the trend and level of antihypertensive medication use in a series of intervention analyses.The number of antihypertensive drugs used increased as patients neared ESRD, peaking at an average of 3.4 in the quarter immediately preceding dialysis initiation, then declining to 2.2 medications by 2 years later. Angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use was stable at approximately 40%, even among patients with coronary disease and systolic heart failure, and did not correlate with AKI or hyperkalemia. Dialysis initiation was associated with a 40% (95% confidence interval, 38% to 43%) lower adjusted level of diuretic use, which continued to decline after ESRD. Three- and four-drug combinations that included a diuretic were most common before ESRD, whereas after ESRD, one- and two-drug β-blocker or calcium-channel blocker-based combinations were most common.The use of antihypertensive medications, particularly angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers and diuretics, may be suboptimal during the transition from CKD to ESRD, especially in patients with coronary disease or systolic heart failure. Future studies are needed to identify strategies to increase the appropriate use of antihypertensive medications during this critical transition period.

    View details for DOI 10.2215/CJN.10611015

    View details for PubMedID 27354656

  • Comparative effectiveness of angiotensin receptor blockers vs. angiotensin-converting enzyme inhibitors on cardiovascular outcomes in patients initiating peritoneal dialysis. Journal of nephrology Shen, J. I., Saxena, A. B., Montez-Rath, M. E., Leng, L., Chang, T. I., Winkelmayer, W. C. 2016: -?

    Abstract

    There is evidence that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) may reduce cardiovascular (CV) risk in patients undergoing peritoneal dialysis (PD), but no studies have compared the effectiveness between these drug classes. In this observational cohort study, we compared the association of ARB vs. ACEI use on CV outcomes in patients initiating PD.We identified from the US Renal Data System all adult patients who initiated PD from 2007 to 2011 and participated in Medicare Part D, a federal prescription drug benefits program, for the first 90 days of dialysis. Patients who filled a prescription for an ACEI or ARB in those 90 days were considered users. We excluded patients who used both ACEI and ARB. We applied Cox proportional hazards regression to an inverse probability of treatment-weighted cohort to estimate the hazard ratios (HR) for the combined outcome of all-cause death, ischemic stroke, or myocardial infarction; all-cause mortality; and CV death.Among 1892 patients using either drug class, 39 % were ARB users. We observed 624 events over 2,898 person-years of follow-up, for a composite event rate of 22 events per 100 person-years. We observed no differences between ARB vs. ACEI users: composite outcome HR 0.94, 95 % confidence interval (CI) 0.79-1.11; all-cause mortality HR 0.92, 95 % CI 0.76-1.10; CV death HR: 1.06, 95 % CI 0.80-1.41.We identified no significant difference in the risks of CV events or death between users of ARBs vs. ACEIs in patients initiating PD, thus supporting their mostly interchangeable use in this population.

    View details for PubMedID 27485007

  • Recovery From Acute Kidney Injury and CKD Following Heart Transplantation in Children, Adolescents, and Young Adults: A Retrospective Cohort Study. American journal of kidney diseases Hollander, S. A., Montez-Rath, M. E., Axelrod, D. M., Krawczeski, C. D., May, L. J., Maeda, K., Rosenthal, D. N., Sutherland, S. M. 2016; 68 (2): 212-218

    Abstract

    Acute kidney injury (AKI) is common in children following surgery for congenital heart disease and has been associated with poor long-term kidney outcomes. Children undergoing heart transplantation may be at increased risk for the development of both AKI and chronic kidney disease (CKD). This study examines AKI rates in children, adolescents, and young adults after heart transplantation and analyzes the relationship between AKI and CKD in this population.Retrospective cohort study.88 young patients who underwent heart transplantation at Lucile Packard Children's Hospital, Stanford, CA, September 1, 2007, to November 30, 2013.The primary independent variable was AKI within the first 7 postoperative days, ascertained according to the KDIGO (Kidney Disease: Improving Global Outcomes) creatinine criteria (increase in serum creatinine ≥ 1.5 times baseline within 7 days).Recovery from AKI at 3 months, ascertained as serum creatinine level < 1.5 times baseline; and development of CKD at 6 and 12 months, ascertained as estimated glomerular filtration rate < 60mL/min/1.73m(2) for more than 3 months.63 (72%) patients developed AKI; 57% had moderate (stage 2 or severe stage 3) disease. Recovery occurred in 39 of 63 (62%), 50% for stage 2 or 3 versus 78% for stage 1 (P=0.04). At 6 and 12 months, 3 of 82 (4%) and 4 of 76 (5%) developed CKD, respectively. At both time points, CKD was more common in those without recovery (3/22 [14%] vs 0/38 (0%); P=0.04, and 3/17 (18%) vs (0/34) 0%; P=0.03, respectively).Retrospective design, small sample size, and single-center nature of the study.AKI is common after heart transplantation in children, adolescents, and young adults. Nonrecovery from AKI is more common in patients with more severe AKI and is associated with the development of CKD during the first year.

    View details for DOI 10.1053/j.ajkd.2016.01.024

    View details for PubMedID 26970941

  • Rates and Outcomes of Parathyroidectomy for Secondary Hyperparathyroidism in the United States CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kim, S. M., Long, J., Montez-Rath, M. E., Leonard, M. B., Norton, J. A., Chertow, G. M. 2016; 11 (7): 1260-1267

    Abstract

    Secondary hyperparathyroidism is common among patients with ESRD. Although medical therapy for secondary hyperparathyroidism has changed dramatically over the last decade, rates of parathyroidectomy for secondary hyperparathyroidism across the United States population are unknown. We examined temporal trends in rates of parathyroidectomy, in-hospital mortality, length of hospital stay, and costs of hospitalization.Using the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, a representative national database on hospital stay regardless of age and payer in the United States, we identified parathyroidectomies for secondary hyperparathyroidism from 2002 to 2011. Data from the US Renal Data System reports were used to calculate the rate of parathyroidectomy.We identified 32,971 parathyroidectomies for secondary hyperparathyroidism between 2002 and 2011. The overall rate of parathyroidectomy was approximately 5.4/1000 patients (95% confidence interval [95% CI], 5.0/1000 to 6.0/1000). The rate decreased from 2003 (7.9/1000 patients; 95% CI, 6.2/1000 to 9.6/1000), reached a nadir in 2005 (3.3/1000 patients; 95% CI, 2.6/1000 to 4.0/1000), increased again through 2006 (5.4/1000 patients; 95% CI, 4.4/1000 to 6.4/1000), and remained stable since that time. Rates of in-hospital mortality decreased from 1.7% (95% CI, 0.8% to 2.6%) in 2002 to 0.8% (95% CI, 0.1% to 1.6%) in 2011 (P for trend <0.001). In-hospital mortality rates were significantly higher in patients with heart failure (odds ratio [OR], 4.23; 95% CI, 2.59 to 6.91) and peripheral vascular disease (OR, 4.59; 95% CI, 2.75 to 7.65) and lower among patients with prior kidney transplantation (OR, 0.20; 95% CI, 0.06 to 0.65).Despite the use of multiple medical therapies, rates of parathyroidectomy of secondary hyperparathyroidism have not declined in recent years.

    View details for DOI 10.2215/CJN.10370915

    View details for PubMedID 27269300

  • The win ratio approach to analyzing composite outcomes: An application to the EVOLVE trial CONTEMPORARY CLINICAL TRIALS Abdalla, S., Montez-Rath, M. E., Parfrey, P. S., Chertow, G. M. 2016; 48: 119-124

    Abstract

    Unlike conventional time-to-event analysis of composite endpoints in clinical trials, the "win ratio" method allows for flexibility in prioritizing their components. Here, we compare the EVOLVE trial findings using the win ratio with those from time-to-event analysis.Randomization to cinacalcet or placebo.The primary composite endpoint combining all-cause mortality and non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, and peripheral vascular events.In an unadjusted analysis, we paired each participant from the cinacalcet arm with every participant from the placebo arm within randomization strata. Pairs were classified as "winners" or "losers," according to which participant died first during the shared follow-up time, or experienced the next ranked event first. We ranked non-fatal events in two ways: 1) all ranked evenly; and 2) prioritized by their effect on health-related quality of life. The win ratio equaled the total winners divided by total losers. Further analyses were conducted where the win ratio was stratified by, or adjusted for, age.The unadjusted win ratio for the primary composite endpoint was 1.09 (95% CI 0.97 to 1.21), a statistically non-significant result which supports the primary trial result - unadjusted hazard ratio 0.93 (95% CI 0.85 to 1.02). Age-stratified analyses showed a nominally significant benefit of cinacalcet (win ratio 1.14, 95% CI 1.04 to 1.26). Ranking of non-fatal outcomes by their relative effects on quality of life did not materially alter the results.The win ratio method corroborated the findings of EVOLVE based on conventional time-to-event analysis. EVOLVE ClinicalTrials.gov number: NCT00345839.

    View details for DOI 10.1016/j.cct.2016.04.001

    View details for PubMedID 27080930

  • DIFFERENCES IN PATIENT AND ALLOGRAFT SURVIVAL FOLLOWING KIDNEY TRANSPLANTATION AMONG GLOMERULONEPHRITIS SUBTYPES IN THE UNITED STATES. O'Shaughnessy, M., Montez-Rath, M., Liu, S., Lafayette, R., Winkelmayer, W. W B SAUNDERS CO-ELSEVIER INC. 2016: A82
  • Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Shen, J. I., Saxena, A. B., Montez-Rath, M. E., Chang, T. I., Winkelmayer, W. C. 2016

    Abstract

    Data on the effectiveness of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in reducing cardiovascular (CV) risk in patients undergoing peritoneal dialysis (PD) are limited. We investigated the association between ACEI/ARB use and CV outcomes in patients initiating PD.In this observational cohort study, we identified from the United States Renal Data System all adult patients who initiated PD from 2007 to 2011 and participated in Medicare Part D, a federal prescription drug benefits program, for the first 90 days of dialysis. Patients who filled a prescription for an ACEI or ARB in those 90 days were considered users. We applied Cox regression to an inverse probability of treatment weighted cohort to estimate the hazard ratios (HRs) for the combined outcome of death, ischemic stroke or myocardial infarction (MI) and each outcome individually.Among 4879 patients, 2063 (42%) used an ACEI/ARB. Patients were followed up for a median of 1.2 years. We recorded 1771 events, for a composite rate of 25 events per 100 person-years. ACEI/ARB use (versus nonuse) was associated with a reduced risk of the composite outcome {HR 0.84 [95% confidence interval (CI) 0.76-0.93]}, all-cause mortality [HR 0.83 (95% CI 0.75-0.92)] and CV death [HR 0.74 (95% CI 0.63-0.87)], but not MI [HR 0.88 (95% CI 0.69-1.12)] or ischemic stroke [HR 1.06 (95% CI 0.79-1.43)]. Results were similar in as-treated analyses. In a subgroup analysis, we did not find any effect modification by residual renal function.ACEI/ARB use is common in patients initiating PD and is associated with a lower risk of fatal CV outcomes.

    View details for PubMedID 27190342

  • Impact of ventricular assist device placement on longitudinal renal function in children with end-stage heart failure. journal of heart and lung transplantation May, L. J., Montez-Rath, M. E., Yeh, J., Axelrod, D. M., Chen, S., Maeda, K., Almond, C. S., Rosenthal, D. N., Hollander, S. A., Sutherland, S. M. 2016; 35 (4): 449-456

    Abstract

    Although ventricular assist devices (VADs) restore hemodynamics in those with heart failure, reversibility of end-organ dysfunction with VAD support is not well characterized. Renal function often improves in adults after VAD placement, but this has not been comprehensively explored in children.Sixty-three children on VAD support were studied. Acute kidney injury (AKI) was defined by Kidney Disease: Improving Global Outcomes criteria. Estimated glomerular filtration rate (eGFR) was determined by the Schwartz method. Generalized linear mixed-effects models compared the pre-VAD and post-VAD eGFR for the cohort and sub-groups with and without pre-VAD renal dysfunction (pre-VAD eGFR < 90 ml/min/1.73 m(2)).The pre-VAD eGFR across the cohort was 84.0 ml/min/1.73 m(2) (interquartile range [IQR] 62.3-122.7), and 55.6% (34 of 63) had pre-VAD renal dysfunction. AKI affected 60.3% (38 of 63), with similar rates in those with and without pre-existing renal dysfunction. Within the cohort, the nadir eGFR occurred 1 day post-operatively (62.9 ml/min/1.73 m(2); IQR, 51.2-88.9 ml/min/1.73 m(2); p < 0.001). By Day 5, however, the eGFR exceeded the baseline (99.0 ml/min/1.73 m(2); IQR, 59.3-146.7 ml/min/1.73 m(2); p = 0.03) and remained significantly higher through the first post-operative week. After adjusting for age, gender, and AKI, the eGFR continued to increase throughout the entire 180-day study period (β = 0.0025; 95% confidence interval, 0.0015-0.0036; p < 0.001). Patients with pre-VAD renal dysfunction experienced the greatest improvement in the eGFR (β = 0.0051 vs β = 0.0013, p < 0.001).Renal dysfunction is prevalent in children with heart failure undergoing VAD placement. Although peri-operative AKI is common, renal function improves substantially in the first post-operative week and for months thereafter. This is particularly pronounced in those with pre-VAD renal impairment, suggesting that VADs may facilitate recovery and maintenance of kidney function in children with advanced heart failure.

    View details for DOI 10.1016/j.healun.2015.10.039

    View details for PubMedID 26653933

  • Differences in Initial Hemodialysis Vascular Access Use Among Glomerulonephritis Subtypes in the United States. American journal of kidney diseases O'Shaughnessy, M. M., Montez-Rath, M. E., Zheng, Y., Lafayette, R. A., Winkelmayer, W. C. 2016; 67 (4): 638-647

    Abstract

    The type of vascular access used for hemodialysis affects patient morbidity and mortality. Whether vascular access types differ by glomerulonephritis (GN) subtype in the US hemodialysis population has not been investigated.Cross-sectional observational study.We identified all adult (aged ≥ 18 years) patients within the US Renal Data System who initiated hemodialysis therapy from July 2005 through December 2011 with a diagnosis of end-stage renal disease attributed to any of 4 primary (focal segmental glomerulosclerosis, immunoglobulin A nephropathy [reference group], membranous nephropathy, and membranoproliferative GN) or 2 secondary (lupus nephritis and vasculitis) GN subtypes.GN subtype.ORs with 95% CIs for arteriovenous fistula versus central venous catheter (CVC) use and for arteriovenous graft versus CVC use were computed using multinomial logistic regression, with adjustment for demographic, socioeconomic, comorbidity, and duration of nephrology care covariates.Among 29,015 patients, CVC use at initiation of hemodialysis therapy was substantially higher in patients with lupus nephritis (89.2%) or vasculitis (91.2%) compared with patients with primary GN subtypes (72.7%-79.8%). After adjustment and compared with patients with immunoglobulin A nephropathy, patients with lupus nephritis or vasculitis were as likely to have used an arteriovenous graft (ORs of 0.94 [95% CI, 0.70-1.27] and 0.80 [95% CI, 0.56-1.13], respectively) but significantly less likely to have used an arteriovenous fistula (ORs of 0.66 [95% CI, 0.57-0.76] and 0.54 [95% CI, 0.45-0.63], respectively), whereas patients with any comparator primary GN subtype were at least as likely to have used either of these 2 access types.Potential misclassification of exposure; residual confounding by unmeasured covariates; inability to determine causes of observed associations; lacking longitudinal data for vascular access use.Significant differences in vascular access distributions at initiation of hemodialysis therapy are apparent among GN subtypes. The unacceptably high use of CVCs in patients with lupus nephritis and vasculitis is particularly concerning. Further studies are needed to identify any potentially modifiable factors underlying these findings.

    View details for DOI 10.1053/j.ajkd.2015.11.019

    View details for PubMedID 26774466

  • Drug-Eluting Versus Bare-Metal Stents During PCI in Patients With End-Stage Renal Disease on Dialysis JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Chang, T. I., Montez-Rath, M. E., Tsai, T. T., Hlatky, M. A., Winkelmayer, W. C. 2016; 67 (12): 1459-1469

    Abstract

    In patients undergoing percutaneous coronary intervention (PCI), drug-eluting stents (DES) reduce repeat revascularizations compared with bare-metal stents (BMS), but their effects on death and myocardial infarction (MI) are mixed. Few studies have focused on patients with end-stage renal disease.This study compared mortality and cardiovascular morbidity during percutaneous coronary intervention with DES and with BMS in dialysis patients.We identified 36,117 dialysis patients from the USRDS (United States Renal Data System) who had coronary stenting in the United States between April 23, 2003, and December 31, 2010, and examined the association of DES versus BMS with 1-year outcomes: death; death or MI; and death, MI, or repeat revascularization. We also conducted a temporal analysis by dividing the study period into 3 DES eras: Transitional (April 23, 2003, to June 30, 2004); Liberal (July 1, 2004, to December 31, 2006); and Selective (January 1, 2007, to December 31, 2010).One-year event rates were high, with 38 deaths; 55 death or MI events; and 71 death, MI, or repeat revascularization events per 100 person-years. DES, compared with BMS, were associated with a significant 18% lower risk of death; 16% lower risk of death or MI; and 13% lower risk of death, MI, or repeat revascularization. DES use varied, from 56% in the Transitional era to 85% in the Liberal era and 62% in the Selective era. DES outcomes in the Liberal era were significantly better than in the Transitional Era, but not significantly better than in the Selective Era.DES for percutaneous coronary intervention appears to be safe for use in U.S. dialysis patients and is associated with lower rates of death, MI, and repeat revascularization.

    View details for DOI 10.1016/j.jacc.2015.10.104

    View details for Web of Science ID 000372408500011

    View details for PubMedCentralID PMC4808241

  • Sleep disordered breathing and cardiovascular risk in older patients initiating dialysis in the United States: a retrospective observational study using medicare data BMC NEPHROLOGY Tuohy, C. V., Montez-Rath, M. E., Turakhia, M., Chang, T. I., Winkelman, J. W., Winkelmayer, W. C. 2016; 17

    Abstract

    Sleep disordered breathing (SDB) such as sleep apnea is associated with cardiovascular disease in the general population. However, little is known about the cardiovascular risks of SDB in patients with end-stage renal disease (ESRD).We identified Medicare fee-for-service beneficiaries aged ≥67 years initiating dialysis between 2004 and 2009. Outcomes of interest included all-cause mortality, incident myocardial infarction, ischemic stroke, and atrial fibrillation. We compared patients with and without diagnosed SDB using Cox proportional hazards regression.Between 2004 and 2009, 184,217 older patients developed ESRD, of whom 15,121 (8.2 %) were previously diagnosed with SDB. Patients diagnosed with SDB were younger, more likely to be male and Caucasian, less Medicaid eligible, had more non-Nephrology clinic visits, higher body mass index, and more comorbidity. In analyses adjusting for demographics and BMI, diagnosed SDB was associated with higher risk of death and atrial fibrillation, but not associated with myocardial infarction or ischemic stroke risk. After further adjustment for all baseline characteristics, diagnosed SDB was associated with slightly lower risks of death (hazard ratio [HR]: 0.93, 95 % confidence interval [CI]: 0.91-0.96), myocardial infarction (HR: 0.92, CI: 0.87-0.98), and ischemic stroke (HR: 0.90, 95 % CI: 0.82-0.98), and not associated with atrial fibrillation (HR: 1.02, CI: 0.98-1.07).In older patients initiating dialysis in the U.S., diagnosed SDB was weakly associated with lower risks of death and important cardiovascular outcomes, thus adding to the list of established risk factors that are paradoxically associated with cardiovascular outcomes in the ESRD population.

    View details for DOI 10.1186/s12882-016-0229-3

    View details for Web of Science ID 000369620700001

    View details for PubMedCentralID PMC4748630

  • Sleep disordered breathing and cardiovascular risk in older patients initiating dialysis in the United States: a retrospective observational study using medicare data. BMC nephrology Tuohy, C. V., Montez-Rath, M. E., Turakhia, M., Chang, T. I., Winkelman, J. W., Winkelmayer, W. C. 2016; 17: 16

    Abstract

    Sleep disordered breathing (SDB) such as sleep apnea is associated with cardiovascular disease in the general population. However, little is known about the cardiovascular risks of SDB in patients with end-stage renal disease (ESRD).We identified Medicare fee-for-service beneficiaries aged ≥67 years initiating dialysis between 2004 and 2009. Outcomes of interest included all-cause mortality, incident myocardial infarction, ischemic stroke, and atrial fibrillation. We compared patients with and without diagnosed SDB using Cox proportional hazards regression.Between 2004 and 2009, 184,217 older patients developed ESRD, of whom 15,121 (8.2 %) were previously diagnosed with SDB. Patients diagnosed with SDB were younger, more likely to be male and Caucasian, less Medicaid eligible, had more non-Nephrology clinic visits, higher body mass index, and more comorbidity. In analyses adjusting for demographics and BMI, diagnosed SDB was associated with higher risk of death and atrial fibrillation, but not associated with myocardial infarction or ischemic stroke risk. After further adjustment for all baseline characteristics, diagnosed SDB was associated with slightly lower risks of death (hazard ratio [HR]: 0.93, 95 % confidence interval [CI]: 0.91-0.96), myocardial infarction (HR: 0.92, CI: 0.87-0.98), and ischemic stroke (HR: 0.90, 95 % CI: 0.82-0.98), and not associated with atrial fibrillation (HR: 1.02, CI: 0.98-1.07).In older patients initiating dialysis in the U.S., diagnosed SDB was weakly associated with lower risks of death and important cardiovascular outcomes, thus adding to the list of established risk factors that are paradoxically associated with cardiovascular outcomes in the ESRD population.

    View details for DOI 10.1186/s12882-016-0229-3

    View details for PubMedID 26861778

    View details for PubMedCentralID PMC4748630

  • Differences in initial treatment modality for end-stage renal disease among glomerulonephritis subtypes in the USA. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association O'Shaughnessy, M. M., Montez-Rath, M. E., Lafayette, R. A., Winkelmayer, W. C. 2016; 31 (2): 290-298

    Abstract

    Kidney transplantation is the preferred treatment for end-stage renal disease (ESRD), while peritoneal dialysis affords certain benefits over hemodialysis. Distributions and determinants of first ESRD treatment modality have not been compared across glomerulonephritis (GN) subtypes.We identified all adult (18-75 years) patients with ESRD attributed to any of six GN subtypes [focal segmental glomerulosclerosis (FSGS), IgA nephropathy (IgAN), membranous nephropathy (MN), membranoproliferative GN (MPGN), lupus nephritis (LN) and vasculitis] who were first registered in the US Renal Data System (USRDS) between 1996 and 2011. We used multinomial logistic regression-adjusting for temporal, geographic, demographic, socioeconomic and comorbid factors-to determine odds ratios (ORs) with 95% confidence intervals (CIs) for transplantation versus hemodialysis, and for peritoneal dialysis versus hemodialysis, comparing other GN subtypes to IgAN.Among the 75 278 patients studied, patients with comparator GN subtypes were significantly less likely than those with IgAN to receive either transplantation or peritoneal dialysis. After adjusting for potentially confounding covariates, patients with comparator primary GN subtypes (FSGS, MN, MPGN) were at least as likely to receive transplantation [FSGS OR 0.98 (95% CI 0.93-1.15), MN OR 1.19 (95% CI 1.01-1.39), MPGN OR 1.08 (95% CI 0.93-1.26)] or peritoneal dialysis [FSGS OR 1.05 (95% CI 0.98-1.12), MN OR 1.30 (95% CI 1.18-1.43), MPGN OR 0.95 (95% CI 0.85-1.06)] as patients with IgAN. Conversely, patients with the secondary GN subtypes LN and vasculitis remained significantly less likely to receive either modality [transplantation OR 0.49 (95% CI 0.43-0.56) for LN and 0.27 (95% CI 0.22-0.34) for vasculitis, peritoneal dialysis OR 0.76 (95% CI 0.70-0.82) for LN and 0.54 (95% CI 0.48-0.60) for vasculitis].Significant differences in ESRD treatment practice patterns are apparent among GN subtypes. To ensure equitable care for all patients, regardless of GN subtype, reasons for observed disparities should be elucidated and-if appropriate-eliminated.

    View details for DOI 10.1093/ndt/gfv386

    View details for PubMedID 26610594

  • Declining Rates of Inpatient Parathyroidectomy for Primary Hyperparathyroidism in the US. PloS one Kim, S. M., Shu, A. D., Long, J., Montez-Rath, M. E., Leonard, M. B., Norton, J. A., Chertow, G. M. 2016; 11 (8)

    Abstract

    Parathyroidectomy is the only curative therapy for patients with primary hyperparathyroidism. However, the incidence, correlates and consequences of parathyroidectomy for primary hyperparathyroidism across the entire US population are unknown. We evaluated temporal trends in rates of inpatient parathyroidectomy for primary hyperparathyroidism, and associated in-hospital mortality, length of stay, and costs. We used the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) from 2002-2011. Parathyroidectomies for primary hyperparathyroidism were identified using International Classification of Diseases, Ninth Revision codes. Unadjusted and age- and sex- adjusted rates of inpatient parathyroidectomy for primary hyperparathyroidism were derived from the NIS and the annual US Census. We estimated 109,583 parathyroidectomies for primary hyperparathyroidism between 2002 and 2011. More than half (55.4%) of patients were younger than age 65, and more than three-quarters (76.8%) were female. The overall rate of inpatient parathyroidectomy was 32.3 cases per million person-years. The adjusted rate decreased from 2004 (48.3 cases/million person-years) to 2007 (31.7 cases/million person-years) and was sustained thereafter. Although inpatient parathyroidectomy rates declined over time across all geographic regions, a steeper decline was observed in the South compared to other regions. Overall in-hospital mortality rates were 0.08%: 0.02% in patients younger than 65 years and 0.14% in patients 65 years and older. Inpatient parathyroidectomy rates for primary hyperparathyroidism have declined in recent years.

    View details for DOI 10.1371/journal.pone.0161192

    View details for PubMedID 27529699

  • Trends in the outcomes of end-stage renal disease secondary to human immunodeficiency virus-associated nephropathy. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Razzak Chaudhary, S., Workeneh, B. T., Montez-Rath, M. E., Zolopa, A. R., Klotman, P. E., Winkelmayer, W. C. 2015; 30 (10): 1734-1740

    Abstract

    Little is known about the trends in the incidence and outcomes of patients with end-stage renal disease (ESRD) attributed to human immunodeficiency virus-associated nephropathy (HIVAN). We sought to define relative incidence among ESRD patients, changes in mortality among patients with ESRD attributed to HIVAN, as well as changes in the excess mortality experienced by patients with ESRD attributed to HIVAN compared with otherwise similar ESRD patients with non-HIVAN causes.We used the US Renal Data System to identify all individuals with reported HIVAN who initiated treatment for ESRD between 1989 and 2011. We plotted their counts and proportions among all incident ESRD patients and tabulated their characteristics across years. We then compared mortality within the HIVAN group across years using Cox regression. In addition, we studied the trends in relative mortality of HIVAN patients versus those with ESRD not reported as HIVAN.Overall, 14 719 individuals with HIVAN-ESRD were recorded, with significant reductions in recent years (893 in 2006; 525 in 2011). Compared with patients initiating dialysis between 1989 and 1992, mortality declined by 40% (HR = 0.60; 95% CI, 0.55-0.65) and 64% (HR = 0.36; 95% CI, 0.32-0.40) for patients initiating dialysis in 1999/2000 and 2009-11, respectively. The adjusted excess mortality of HIVAN-ESRD patients versus incident ESRD patients from other causes was >5-fold in 1989-92 (HR = 5.21; 95% CI, 4.84-5.60); this excess mortality has subsequently declined but remained at almost 3-fold in recent years (e.g. HR = 2.58; 95% CI, 2.37-2.80, 2009-11 incidence cohort).Concurrent with the increasing availability of highly active antiretroviral therapy (HAART), both the incidence of ESRD due to HIVAN and the mortality of such patients have decreased substantially. However, HIVAN patients reaching ESRD continue to experience substantial excess mortality compared with other ESRD patients even in the current era of modern HAART.

    View details for DOI 10.1093/ndt/gfv207

    View details for PubMedID 26175146

  • Trends in the outcomes of end-stage renal disease secondary to human immunodeficiency virus-associated nephropathy NEPHROLOGY DIALYSIS TRANSPLANTATION Chaudhary, S. R., Workeneh, B. T., Montez-Rath, M. E., Zolopa, A. R., Klotman, P. E., Winkelmayer, W. C. 2015; 30 (10): 1734-1740

    View details for DOI 10.1093/ndt/gfv207

    View details for Web of Science ID 000363171900019

  • Outcomes After Warfarin Initiation in a Cohort of Hemodialysis Patients With Newly Diagnosed Atrial Fibrillation. American journal of kidney diseases Shen, J. I., Montez-Rath, M. E., Lenihan, C. R., Turakhia, M. P., Chang, T. I., Winkelmayer, W. C. 2015; 66 (4): 677-688

    Abstract

    Although warfarin is indicated to prevent ischemic strokes in most patients with atrial fibrillation (AF), evidence supporting its use in hemodialysis patients is limited. Our aim was to examine outcomes after warfarin therapy initiation, relative to no warfarin use, following incident AF in a large cohort of hemodialysis patients who had comprehensive prescription drug coverage through Medicare Part D.Retrospective observational cohort study.Patients in the US Renal Data System undergoing maintenance hemodialysis who had AF newly diagnosed in 2007 to 2011, with Medicare Part D coverage, who had no recorded history of warfarin use.Warfarin therapy initiation, identified by a filled prescription within 30 days of the AF event.Death, ischemic stroke, hemorrhagic stroke, severe gastrointestinal bleeding, and composite outcomes.HRs estimated by applying Cox regression to an inverse probability of treatment and censoring-weighted cohort.Of 12,284 patients with newly diagnosed AF, 1,838 (15%) initiated warfarin therapy within 30 days; however, ∼70% discontinued its use within 1 year. In intention-to-treat analyses, warfarin use was marginally associated with a reduced risk of ischemic stroke (HR, 0.68; 95% CI, 0.47-0.99), but not with the other outcomes. In as-treated analyses, warfarin use was associated with reduced mortality (HR, 0.84; 95% CI, 0.73-0.97).Short observation period, limited number of nonfatal events, limited generalizability of results to more affluent patients.In hemodialysis patients with incident AF, warfarin use was marginally associated with reduced risk of ischemic stroke, and there was a signal toward reduced mortality in as-treated analyses. These results support clinical equipoise regarding the use of warfarin in hemodialysis patients and underscore the need for randomized trials to fill this evidence gap.

    View details for DOI 10.1053/j.ajkd.2015.05.019

    View details for PubMedID 26162653

  • Patient Characteristics and Outcomes by GN Subtype in ESRD. Clinical journal of the American Society of Nephrology O'Shaughnessy, M. M., Montez-Rath, M. E., Lafayette, R. A., Winkelmayer, W. C. 2015; 10 (7): 1170-1178

    Abstract

    Outcomes-based research rarely focuses on patients with ESRD caused by GN. The hypotheses were that the GN subtype would clinically discriminate patient groups and independently associate with survival after ESRD therapy initiation.Data were extracted from the US Renal Data System for adult patients with incident (1996-2011) ESRD attributed to six GN subtypes: FSGS, IgA nephropathy (IgAN), membranous nephropathy, membranoproliferative glomeruonephritis, lupus nephritis (LN), and vasculitis. ESRD attributed to diabetes and autosomal dominant polycystic kidney disease served as non-GN comparators. Unadjusted and adjusted mortality hazard ratios (aHRs) with 95% confidence intervals (95% CIs) were estimated using Cox regression (reference, IgAN). Models sequentially adjusted for sociodemographic (model 2), comorbidity/laboratory (model 3), and ESRD treatment modality (model 4) variables.Among 84,301 patients with ESRD attributed to GN, the median age ranged from 39 (LN) to 66 (vasculitis) years, male sex ranged from 18% (LN) to 68% (IgAN), and black race ranged from 7% (IgAN) to 49% (LN). Patients with IgAN had the fewest comorbidities and lowest use of hemodialysis (70.1%). After a median follow-up of 2.5 (interquartile range, 1.0-4.9) years, crude mortality was lowest in IgAN (3.7 deaths/100 person years). Compared to IgAN, adjusted mortality was highest in LN (model 4 aHR=1.75; 95% CI, 1.68 to 1.83) and in diabetes (aHR=1.73; 95% CI, 1.67 to 1.79), and was also higher in all other GN subtypes (membranous nephropathy: aHR=1.23; 95% CI, 1.17 to 1.29; FSGS: aHR=1.37; 95% CI, 1.32 to 1.42; membranoproliferative GN: aHR=1.38; 95% CI, 1.31 to 1.45; vasculitis: aHR=1.51; 95% CI, 1.45 to 1.58) and in autosomal dominant polycystic kidney disease (aHR=1.22; 95% CI, 1.18 to 1.27).This study exposes substantial heterogeneity across GN subtypes at ESRD therapy initiation and identifies independent associations between GN subtype and post-ESRD mortality. These survival discrepancies warrant further study, and the utility of current research practice to group GN subtypes together when evaluating ESRD outcomes should be questioned.

    View details for DOI 10.2215/CJN.11261114

    View details for PubMedID 26092830

    View details for PubMedCentralID PMC4491300

  • Prevalence of chronic kidney disease in two major Indian cities and projections for associated cardiovascular disease KIDNEY INTERNATIONAL Anand, S., Shivashankar, R., Ali, M. K., Kondal, D., Binukumar, B., Montez-Rath, M. E., Ajay, V. S., Pradeepa, R., Deepa, M., Gupta, R., Mohan, V., Narayan, K. M., Tandon, N., Chertow, G. M., Prabhakaran, D. 2015; 88 (1): 178-185

    Abstract

    India is experiencing an alarming rise in the burden of noncommunicable diseases, but data on the incidence of chronic kidney disease (CKD) are sparse. Using the Center for Cardiometabolic Risk Reduction in South Asia surveillance study (a population-based survey of Delhi and Chennai, India) we estimated overall, and age-, sex-, city-, and diabetes-specific prevalence of CKD, and defined the distribution of the study population by the Kidney Disease Improving Global Outcomes (KDIGO) classification scheme. The likelihood of cardiovascular events in participants with and without CKD was estimated by the Framingham and Interheart Modifiable Risk Scores. Of the 12,271 participants, 80% had complete data on serum creatinine and albuminuria. The prevalence of CKD and albuminuria, age standardized to the World Bank 2010 world population, was 8.7% (95% confidence interval: 7.9-9.4%) and 7.1% (6.4-7.7%), respectively. Nearly 80% of patients with CKD had an abnormally high hemoglobin A1c (5.7 and above). Based on KDIGO guidelines, 6.0, 1.0, and 0.5% of study participants are at moderate, high, or very high risk for experiencing CKD-associated adverse outcomes. The cardiovascular risk scores placed a greater proportion of patients with CKD in the high-risk categories for experiencing cardiovascular events when compared with participants without CKD. Thus, 1 in 12 individuals living in two of India's largest cities have evidence of CKD, with features that put them at high risk for adverse outcomes.

    View details for DOI 10.1038/ki.2015.58

    View details for PubMedID 25786102

  • Comparison of longer-term outcomes after kidney transplantation between Hispanic and non-Hispanic whites in the United States. American journal of transplantation Arce, C. M., Lenihan, C. R., Montez-Rath, M. E., Winkelmayer, W. C. 2015; 15 (2): 499-507

    Abstract

    Little is known about the longer-term kidney transplant outcomes in the rapidly growing Hispanic population. Using the United States Renal Data System, we identified 105 250 Caucasian patients who received a first kidney transplant between January 1, 1996 and December 31, 2010. We tested for differences between Hispanic and non-Hispanic patients in the outcomes of (1) mortality, (2) all-cause graft failure, and (3) graft failure excluding death with a functioning graft. We used Cox regression to estimate (with 95% confidence intervals) multivariable-adjusted cause-specific hazard ratios (aHRCS ) for mortality and all-cause graft failure and subdistribution hazard ratios (aHRSD ) accounting for death as a competing risk for graft failure excluding death with a functioning graft. Both mortality [aHRCS  = 0.69 (0.65-0.73)] and all-cause graft failure [aHRCS  = 0.79 (0.75-0.83)] were lower in Hispanics. The association between Hispanic ethnicity and graft failure excluding death was modified by age (p < 0.003). Compared with non-Hispanic whites, graft failure excluding death with a functioning graft did not differ in Hispanics aged 18-39 years [aHRSD  = 0.96 (0.89-1.05)] or aged 40-59 years [aHRSD  = 1.08 (1.00-1.16)], but was 13% lower in those aged ≥60 years [aHRSD  = 0.87 (0.78-0.98)]. In conclusion, once accounting for differences in overall survival, better graft survival was found in older Hispanic patients, but among not those aged <60 years.

    View details for DOI 10.1111/ajt.13043

    View details for PubMedID 25556854

  • Correlates and outcomes of warfarin initiation in kidney transplant recipients newly diagnosed with atrial fibrillation. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Lenihan, C. R., Montez-Rath, M. E., Shen, J. I., Scandling, J. D., Turakhia, M. P., Chang, T. I., Winkelmayer, W. C. 2015; 30 (2): 321-329

    Abstract

    In the kidney transplant population with atrial fibrillation (AF), evidence regarding the effectiveness and safety of warfarin treatment is lacking. We used fee-for-service Medicare claims to identify kidney transplant recipients with newly diagnosed AF from the United States Renal Data System. Warfarin use within 30 days of AF diagnosis was ascertained from Medicare Part D prescription claims (2007-11) or using a validated algorithm (1997-2011). The study end points were (i) the composite of death, stroke or gastrointestinal bleed, (ii) death and (iii) death-censored graft failure. Warfarin user and non-user groups were balanced using inverse probability of treatment weighting and hazard ratios were (HRs) estimated using Cox regression. Among 718 subjects with an indication for anticoagulation, 24% initiated warfarin treatment within 30 days of AF diagnosis. Age was the only independent correlate of warfarin use [odds ratio = 1.02 per year; 95% confidence interval (95% CI) 1.01-1.04]. In the larger cohort of 6492 patients with AF, warfarin use [(23.5%) versus non-use (76.5%)] was associated with small and non-significant reductions in the composite of death, stroke or gastrointestinal bleed (HR = 0.92; 95% CI 0.83-1.02), death (HR = 0.92; 95% CI 0.82-1.02) and death-censored graft failure (HR = 0.90; 95% CI 0.76-1.08). Our study suggests the need for clinical trials of warfarin use in the kidney transplant population with AF.

    View details for DOI 10.1093/ndt/gfu323

    View details for PubMedID 25335507

  • Use of novel oral anticoagulants in patients with end-stage renal disease HEMODIALYSIS INTERNATIONAL Winkelmayer, W. C., Herzog, C. A., Montez-Rath, M. E., Chang, T. I., Chertow, G. M. 2015; 19 (1): 150–53

    View details for PubMedID 25495752

  • Thienopyridine use after coronary stenting in low income patients enrolled in medicare part D receiving maintenance dialysis. Journal of the American Heart Association Chang, T. I., Montez-Rath, M. E., Shen, J. I., Solomon, M. D., Chertow, G. M., Winkelmayer, W. C. 2014; 3 (5)

    Abstract

    Coronary stenting in patients on dialysis has increased by nearly 50% over the past decade, despite heightened risks of associated stent thrombosis and bleeding relative to the general population. We examined clopidogrel, prasugrel or ticlopidine use after percutaneous coronary intervention (PCI) with stenting in patients on dialysis. We conducted 3-, 6-, and 12-month landmark analyses to test the hypothesis that thienopyridine discontinuation prior to those time points would be associated with higher risks of death, myocardial infarction, or repeat revascularization, and a lower risk of major bleeding episodes compared with continued thienopyridine use.Using the US Renal Data System, we identified 8458 patients on dialysis with Medicare Parts A+B+D undergoing PCI with stenting between July 2007 and December 2010. Ninety-nine percent of all thienopyridine prescriptions were for clopidogrel. At 3 months, 82% of patients who received drug-eluting stents (DES) had evidence of thienopyridine use. These proportions fell to 62% and 40% at 6 and 12 months, respectively. In patients who received a bare-metal stent (BMS), 70%, 34%, and 26% of patients had evidence of thienopyridine use at 3, 6, and 12 months, respectively. In patients who received a DES, there was a suggestion of higher risks of death or myocardial infarction associated with thienopyridine discontinuation in the 3-, 6-, and 12-months landmark analyses, but no higher risk of major bleeding episodes. In patients who received a BMS, there were no differences in death or cardiovascular events, and possibly lower risk of major bleeding with thienopyridine discontinuation in the 3- and 6-month landmark analyses.The majority of patients on dialysis who undergo PCI discontinue thienopyridines before 1 year regardless of stent type. While not definitive, these data suggest that longer-term thienopyridine use may be of benefit to patients on dialysis who undergo PCI with DES.

    View details for DOI 10.1161/JAHA.114.001356

    View details for PubMedID 25336465

  • Thienopyridine use after coronary stenting in low income patients enrolled in medicare part D receiving maintenance dialysis. Journal of the American Heart Association Chang, T. I., Montez-Rath, M. E., Shen, J. I., Solomon, M. D., Chertow, G. M., Winkelmayer, W. C. 2014; 3 (5)

    View details for DOI 10.1161/JAHA.114.001356

    View details for PubMedID 25336465

  • 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

  • Correlates and variance decomposition analysis of heparin dosing for maintenance hemodialysis in older US patients. Pharmacoepidemiology and drug safety Shen, J. I., Montez-Rath, M. E., Mitani, A. A., Erickson, K. F., Winkelmayer, W. C. 2014; 23 (5): 515-525

    Abstract

    Heparin is commonly used to anticoagulate the hemodialysis (HD) circuit. Despite the bleeding risk, no American standards exist for its administration. We identified correlates and quantified sources of variance in heparin dosing for HD.We performed a cross-sectional study of patients aged 67 years or older who underwent HD with heparin on one of two randomly chosen days in 2008 at a national chain of dialysis facilities. Using a mixed effects model with random intercept for facility and fixed patient and facility characteristics, we examined heparin dosing at patient and facility levels.The median heparin dose among the 17 722 patients treated in 1366 facilities was 4000 (25th-75th percentile: 2625-6000) units. In multivariable-adjusted analyses, higher weight, longer session duration, catheter use, and dialyzer reuse were significantly associated with higher heparin dose. Dose also varied considerably among census divisions. Of the overall variance in dose, 21% was due to between-facility differences, independent of facilities' case mix, geography, size, or rurality; 79% was due to differences at the patient level. The patient and facility characteristics in our model explained only 25% of the variance at the patient level.Despite the lack of standards for heparin administration, we noted patterns of use, including weight-based and time-dependent dosing. Most of the variance was at the patient level; however, only a quarter of it could be explained. The high amount of unexplained variance suggests that factors other than clinical need are driving heparin dosing and that there is likely room for more judicious dosing of heparin. Copyright © 2014 John Wiley & Sons, Ltd.

    View details for DOI 10.1002/pds.3595

    View details for PubMedID 24677688

  • Temporal trends in the incidence, treatment and outcomes of hip fracture after first kidney transplantation in the United States. American journal of transplantation Sukumaran Nair, S., Lenihan, C. R., Montez-Rath, M. E., Lowenberg, D. W., Chertow, G. M., Winkelmayer, W. C. 2014; 14 (4): 943-951

    Abstract

    It is currently unknown whether any secular trends exist in the incidence and outcomes of hip fracture in kidney transplant recipients (KTR). We identified first-time KTR (1997-2010) who had >1 year of Medicare coverage and no recorded history of hip fracture. New hip fractures were identified from corresponding diagnosis and surgical procedure codes. Outcomes studied included time to hip fracture, type of surgery received and 30-day mortality. Of 69 740 KTR transplanted in 1997-2010, 597 experienced a hip fracture event during 155 341 person-years of follow-up for an incidence rate of 3.8 per 1000 person-years. While unadjusted hip fracture incidence did not change, strong confounding by case mix was present. Using year of transplantation as a continuous variable, the hazard ratio (HR) for hip fracture in 2010 compared with 1997, adjusted for demographic, dialysis, comorbid and most transplant-related factors, was 0.56 (95% confidence interval [CI]: 0.41-0.77). Adjusting for baseline immunosuppression modestly attenuated the HR (0.68; 95% CI: 0.47-0.99). The 30-day mortality was 2.2 (95% CI: 1.3-3.7) per 100 events. In summary, hip fractures remain an important complication after kidney transplantation. Since 1997, case-mix adjusted posttransplant hip fracture rates have declined substantially. Changes in immunosuppressive therapy appear to be partly responsible for these favorable findings.

    View details for DOI 10.1111/ajt.12652

    View details for PubMedID 24712332

  • Addressing Missing Data in Clinical Studies of Kidney Diseases. Clinical journal of the American Society of Nephrology : CJASN Montez-Rath, M. E., Winkelmayer, W. C., Desai, M. 2014

    Abstract

    Missing data constitute a problem present in all studies of medical research. The most common approach to handling missing data-complete case analysis-relies on assumptions about missing data that rarely hold in practice. The implications of this approach are biased and inefficient descriptions of relationships of interest. Here, various approaches for handling missing data in clinical studies are described. In particular, this work promotes the use of multiple imputation methods that rely on assumptions about missingness that are more flexible than those assumptions relied on by the most common method in use. Furthermore, multiple imputation methods are becoming increasingly more accessible in mainstream statistical software packages, making them both a sound and practical choice. The use of multiple imputation methods is illustrated with examples pertinent to kidney research, and concrete guidance on their use is provided.

    View details for DOI 10.2215/CJN.10141013

    View details for PubMedID 24509298

  • Multivessel coronary revascularization and outcomes in kidney transplant recipients. Transplant international Lenihan, C. R., Montez-Rath, M. E., Winkelmayer, W. C., Chang, T. I. 2013; 26 (11): 1080-1087

    Abstract

    Coronary artery disease is a major cause of morbidity and mortality in the kidney transplant population. We compared the long-term outcomes of coronary artery bypass graft (CABG) surgery with percutaneous coronary intervention (PCI) for multivessel coronary disease in a contemporary cohort of US kidney transplant recipients. From the U.S. Renal Data System, we identified all adult kidney transplant patients with ≥6 months of Medicare A+B undergoing first recorded multivessel coronary revascularization from 1997 to 2009. The associations of CABG versus PCI with death and the composite of death or myocardial infarction (MI) were compared using proportional hazards regression. Of the 2272 patients included in the study, 1594 underwent CABG and 678 underwent PCI. The estimated 5-year survival rate was 55% [95% confidence interval (CI) 53% to 57%] following coronary revascularization, with no significant association between revascularization type and death [adjusted hazard ratio (aHR) = 1.08; CI 0.94-1.23] or the composite of death or MI (aHR = 1.07; CI 0.96-1.18). Separate propensity score-matched analyses yielded similar results. In this analysis of kidney transplant recipients undergoing multivessel coronary revascularization, we found no difference between CABG and PCI in terms of survival or the composite of death and MI.

    View details for DOI 10.1111/tri.12168

    View details for PubMedID 23957580

    View details for PubMedCentralID PMC3816637

  • Outcomes after kidney transplantation of patients previously diagnosed with atrial fibrillation. American journal of transplantation Lenihan, C. R., Montez-Rath, M. E., Scandling, J. D., Turakhia, M. P., Winkelmayer, W. C. 2013; 13 (6): 1566-1575

    Abstract

    Little is known about the prevalence and outcomes of patients with atrial fibrillation/flutter (AF) who receive a kidney transplant. We identified all patients who had >1 year of uninterrupted Medicare A+B coverage before receiving their first kidney transplant (1997-2009). The presence of pretransplant AF was ascertained from diagnosis codes in Medicare physician claims. We studied the posttransplant outcomes of death, all-cause graft failure, death-censored graft failure and stroke using multivariable Cox regression. Of 62 706 eligible first kidney transplant recipients studied, 3794 (6.4%) were diagnosed with AF prior to kidney transplant. Over a mean follow up of 4.9 years, 40.6% of AF patients and 24.9% without AF died. All-cause and death-censored graft failure were 46.8% and 16.5%, respectively, in the AF group and 36.4% and 19.5%, respectively, in those without AF. Ischemic stroke occurred in 2.8% of patients with and 1.6% of patients without AF. In patients with AF, multivariable-adjusted hazard ratios (95% confidence intervals) for death, graft failure, death-censored graft failure and ischemic stroke were 1.46 (1.38-1.54), 1.41 (1.34-1.48), 1.26 (1.15-1.37) and 1.36 (1.10-1.68), respectively. Pre-existing AF is associated with poor posttransplant outcomes. Special attention should be paid to AF in pretransplant evaluation, counseling and risk stratification of kidney transplant candidates.

    View details for DOI 10.1111/ajt.12197

    View details for PubMedID 23721555

  • SLEEP DISORDERED BREATHING AND CARDIOVASCULAR RISK IN OLDER PATIENTS INITIATING DIALYSIS Tuohy, C., Montez-Rath, M. E., Turakhia, M., Chang, T. I., Winkelmayer, W. C. W B SAUNDERS CO-ELSEVIER INC. 2013: A95
  • 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
  • Trends in the incidence of intestinal perforation in US dialysis patients (1992-2005). Journal of nephrology Yang, J., Lee, T., Montez-Rath, M. E., Desai, M., Winkelmayer, W. C. 2013; 26 (2): 281-288

    Abstract

    Little is known about the incidence of intestinal perforation in patients undergoing dialysis. Concerns exist that sevelamer hydrochloride may increase the risk of intestinal perforation. We examined long-term trends for the incidence of intestinal perforation among US dialysis patients.We studied all dialysis patients (1992-2005) who had Medicare as primary payer. We used ICD-9 diagnosis code 569.83 to ascertain events of intestinal perforation. We studied (a) all perforations and (b) perforations that did not appear to be associated with specific causative conditions (specific diseases or iatrogenic procedures within 7 days of perforation). We used Poisson regression to model the annual number of intestinal perforations and tested for any changes in levels and temporal trends of incidence rates before versus after January 1, 1999.Overall, 1,060,132 patients contributed 2.7 million patient-years. We observed 12,355 events of intestinal perforation and 7,814 spontaneous perforations. The corresponding incidence rates were 4.6 (total) and 2.9 (spontaneous perforation) episodes per 1,000 person-years, respectively. For both outcome definitions, 30-day mortality was 42%. Unadjusted and adjusted incidence rates were not materially different over time. Formal tests for any changes in the level or slope of incidence comparing time periods before and after January 1, 1999, indicated no evidence for any changes in the incidence of intestinal perforation over time.In US dialysis patients, incidence of intestinal perforation was low, but associated with high short-term mortality. We did not detect any significant changes in the incidence of intestinal perforation before versus after approval of sevelamer hydrochloride in late 1998.

    View details for DOI 10.5301/jn.5000104

    View details for PubMedID 22419235

  • Trends in acute kidney injury, associated use of dialysis, and mortality after cardiac surgery, 1999 to 2008. Annals of thoracic surgery Lenihan, C. R., Montez-Rath, M. E., Mora Mangano, C. T., Chertow, G. M., Winkelmayer, W. C. 2013; 95 (1): 20-28

    Abstract

    The development of acute kidney injury (AKI) after cardiac surgery is associated with significant mortality, morbidity, and cost. The last decade has seen major changes in the complexity of cardiac surgical candidates and in the number and type of cardiac surgical procedures being performed.Using data from the Nationwide Inpatient Sample, we determined the annual rates of AKI, AKI requiring dialysis (AKI-D), and inpatient mortality after cardiac surgery in the United States in the years 1999 through 2008.Inpatient mortality with AKI and AKI-D decreased from 27.9% and 45.9%, respectively, in 1999 to 12.8% and 35.3%, respectively, in 2008. Compared with 1999, the odds of AKI and AKI-D in 2008, adjusted for demographic and clinical factors, were 3.30 (95% confidence interval [CI]: 2.89 to 3.77) and 2.23 (95% CI: 1.78 to 2.80), respectively. Corresponding adjusted odds of death associated with AKI and AKI-D were 0.31 (95% CI: 0.26 to 0.36) and 0.47 (95% CI: 0.34 to 0.65.) Taken together, the attributable risks for death after cardiac surgery associated with AKI and AKI-D increased from 30% and 5%, respectively, in 1999 to 47% and 14%, respectively, in 2008.In sum, despite improvements in individual patient outcomes over the decade 1999 to 2008, the population contribution of AKI and AKI-D to inpatient mortality after surgery increased over the same period.

    View details for DOI 10.1016/j.athoracsur.2012.05.131

    View details for PubMedID 23272825

  • Trends in Acute Kidney Injury, Associated Use of Dialysis, and Mortality After Cardiac Surgery, 1999 to 2008 ANNALS OF THORACIC SURGERY Lenihan, C. R., Montez-Rath, M. E., Mangano, C. T., Chertow, G. M., Winkelmayer, W. C. 2013; 95 (1): 20-28

    Abstract

    The development of acute kidney injury (AKI) after cardiac surgery is associated with significant mortality, morbidity, and cost. The last decade has seen major changes in the complexity of cardiac surgical candidates and in the number and type of cardiac surgical procedures being performed.Using data from the Nationwide Inpatient Sample, we determined the annual rates of AKI, AKI requiring dialysis (AKI-D), and inpatient mortality after cardiac surgery in the United States in the years 1999 through 2008.Inpatient mortality with AKI and AKI-D decreased from 27.9% and 45.9%, respectively, in 1999 to 12.8% and 35.3%, respectively, in 2008. Compared with 1999, the odds of AKI and AKI-D in 2008, adjusted for demographic and clinical factors, were 3.30 (95% confidence interval [CI]: 2.89 to 3.77) and 2.23 (95% CI: 1.78 to 2.80), respectively. Corresponding adjusted odds of death associated with AKI and AKI-D were 0.31 (95% CI: 0.26 to 0.36) and 0.47 (95% CI: 0.34 to 0.65.) Taken together, the attributable risks for death after cardiac surgery associated with AKI and AKI-D increased from 30% and 5%, respectively, in 1999 to 47% and 14%, respectively, in 2008.In sum, despite improvements in individual patient outcomes over the decade 1999 to 2008, the population contribution of AKI and AKI-D to inpatient mortality after surgery increased over the same period.

    View details for DOI 10.1016/j.athoracsur.2012.05.131

    View details for Web of Science ID 000313343700013

  • Risk factors of short-term mortality after acute nonvariceal upper gastrointestinal bleeding in patients on dialysis: a population-based study. BMC nephrology Yang, J., Lee, T., Montez-Rath, M. E., Chertow, G. M., Winkelmayer, W. C. 2013; 14: 97-?

    View details for DOI 10.1186/1471-2369-14-97

    View details for PubMedID 23621917

  • Risk factors of short-term mortality after acute nonvariceal upper gastrointestinal bleeding in patients on dialysis: a population-based study. BMC nephrology Yang, J., Lee, T., Montez-Rath, M. E., Chertow, G. M., Winkelmayer, W. C. 2013; 14: 97-?

    Abstract

    Impaired kidney function is an established predictor of mortality after acute nonvariceal upper gastrointestinal bleeding (ANVUGIB); however, which factors are associated with mortality after ANVUGIB among patients undergoing dialysis is unknown. We examined the associations among demographic characteristics, dialysis-specific features, and comorbid conditions with short-term mortality after ANVUGIB among patients on dialysis.Design: Retrospective cohort study. Setting: United States Renal Data System (USRDS), a nation-wide registry of patients with end-stage renal disease. Participants: All ANVUGIB episodes identified by validated algorithms in Medicare-covered patients between 2003 and 2007. Measurements: Demographic characteristics and comorbid conditions from 1 year of billing claims prior to each bleeding event. We used logistic regression extended with generalized estimating equations methods to model the associations among risk factors and 30-day mortality following ANVUGIB events.From 2003 to 2007, we identified 40,016 eligible patients with 50,497 episodes of ANVUGIB. Overall 30-day mortality was 10.7% (95% CI: 10.4-11.0). Older age, white race, longer dialysis vintage, peritoneal dialysis (vs. hemodialysis), and hospitalized (vs. outpatient) episodes were independently associated with a higher risk of 30-day mortality. Most but not all comorbid conditions were associated with death after ANVUGIB. The joint ability of all factors captured to discriminate mortality was modest (c=0.68).We identified a profile of risk factors for 30-day mortality after ANVUGIB among patients on dialysis that was distinct from what had been reported in non-dialysis populations. Specifically, peritoneal dialysis and more years since initiation of dialysis were independently associated with short-term death after ANVUGIB.

    View details for DOI 10.1186/1471-2369-14-97

    View details for PubMedID 23621917

  • Multivessel Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention in ESRD JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chang, T. I., Shilane, D., Kazi, D. S., Montez-Rath, M. E., Hlatky, M. A., Winkelmayer, W. C. 2012; 23 (12): 2042-2049

    Abstract

    Thirty to sixty percent of patients with ESRD on dialysis have coronary heart disease, but the optimal strategy for coronary revascularization is unknown. We used data from the United States Renal Data System to define a cohort of 21,981 patients on maintenance dialysis who received initial coronary revascularization with either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) between 1997 and 2009 and had at least 6 months of prior Medicare coverage as their primary payer. The primary outcome was death from any cause, and the secondary outcome was a composite of death or myocardial infarction. Overall survival rates were consistently poor during the study period, with unadjusted 5-year survival rates of 22%-25% irrespective of revascularization strategy. Using multivariable-adjusted proportional hazards regression, we found that CABG compared with PCI associated with significantly lower risks for both death (HR=0.87, 95% CI=0.84-0.90) and the composite of death or myocardial infarction (HR=0.88, 95% CI=0.86-0.91). Results were similar in analyses using a propensity score-matched cohort. In the absence of data from randomized trials, these results suggest that CABG may be preferred over PCI for multivessel coronary revascularization in appropriately selected patients on maintenance dialysis.

    View details for DOI 10.1681/ASN.2012060554

    View details for Web of Science ID 000311819000017

    View details for PubMedID 23204445

    View details for PubMedCentralID PMC3507369

  • Trends in Acute Nonvariceal Upper Gastrointestinal Bleeding in Dialysis Patients JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Yang, J., Lee, T., Montez-Rath, M. E., Paik, J., Chertow, G. M., Desai, M., Winkelmayer, W. C. 2012; 23 (3): 495-506

    Abstract

    Impaired kidney function is a risk factor for upper gastrointestinal (GI) bleeding, an event associated with poor outcomes. The burden of upper GI bleeding and its effect on patients with ESRD are not well described. Using data from the US Renal Data System, we quantified the rates of occurrence of and associated 30-day mortality from acute, nonvariceal upper GI bleeding in patients undergoing dialysis; we used medical claims and previously validated algorithms where available. Overall, 948,345 patients contributed 2,296,323 patient-years for study. The occurrence rates for upper GI bleeding were 57 and 328 episodes per 1000 person-years according to stringent and lenient definitions of acute, nonvariceal upper GI bleeding, respectively. Unadjusted occurrence rates remained flat (stringent) or increased (lenient) from 1997 to 2008; after adjustment for sociodemographic characteristics and comorbid conditions, however, we found a significant decline for both definitions (linear approximation, 2.7% and 1.5% per year, respectively; P<0.001). In more recent years, patients had higher hematocrit levels before upper GI bleeding episodes and were more likely to receive blood transfusions during an episode. Overall 30-day mortality was 11.8%, which declined significantly over time (relative declines of 2.3% or 2.8% per year for the stringent and lenient definitions, respectively). In summary, despite declining trends worldwide, crude rates of acute, nonvariceal upper GI bleeding among patients undergoing dialysis have not decreased in the past 10 years. Although 30-day mortality related to upper GI bleeding declined, perhaps reflecting improvements in medical care, the burden on the ESRD population remains substantial.

    View details for DOI 10.1681/ASN.2011070658

    View details for PubMedID 22266666