Calyani Ganesan

All Publications

• Variation in Urology Care after Urinary Stone Surgery among Veterans at High-risk for Recurrence. Urology Ganesan, C., Shahzad, S. R., Thomas, I. C., Montez-Rath, M. E., Soerensen, S. J., Chertow, G. M., Pao, A. C., Leppert, J. T. 2024

  Abstract

  To determine rates of urology follow-up and implementation of stone prevention measures after stone surgery and to assess variation in care delivery within a large, integrated healthcare system.We used nationwide data from the United States Veterans Health Administration to identify patients who had stone surgery between 2016 and 2018 and who were at higher risk for recurrence. Our cohort included 13,444 Veterans across 90 facilities. We examined the proportion of patients who had a post-operative urology visit or who received a prevention measure (24-hour urine test, serum parathyroid hormone measurement, or prescription of a stone-related medication) within 6 months of stone surgery. We calculated the median odds ratio to quantify facility-level variation in urology care after stone surgery, adjusting for patient- and facility-level characteristics.Within 6 months of stone surgery, 94.2% Veterans had a urology visit, yet only 8.8% completed 24-hour urine testing, 8.4% had a parathyroid hormone measurement, and 31.0% were prescribed a stone-related medication. Implementation of prevention measures varied widely across facilities with the median odds ratio ranging between 1.18 for medication prescriptions and 1.77 for 24-hour urine testing.While most patients have a urology visit after stone surgery, stone prevention measures were implemented infrequently and inconsistently for patients at higher risk for recurrence, indicating an opportunity for quality improvement.

  View details for DOI 10.1016/j.urology.2024.10.012

  View details for PubMedID 39419204

• The Clinical Study of Kidney Stone Disease and the Value of Specificity. Clinical journal of the American Society of Nephrology : CJASN Pao, A. C., Ganesan, C. 2024

  View details for DOI 10.2215/CJN.0000000000000459

  View details for PubMedID 38629855

• 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

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

  View details for DOI 10.7326/L23-0280

  View details for PubMedID 37983791

• The Nephrologist's Role in the Management of Kidney Cancer: A Renaissance. American journal of kidney diseases : the official journal of the National Kidney Foundation Ganesan, C., Pao, A. C., Leppert, J. T. 2023

  View details for DOI 10.1053/j.ajkd.2023.08.003

  View details for PubMedID 37855784

• 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

• A widely distributed gene cluster compensates for uricase loss in hominids. Cell Liu, Y., Jarman, J. B., Low, Y. S., Augustijn, H. E., Huang, S., Chen, H., DeFeo, M. E., Sekiba, K., Hou, B. H., Meng, X., Weakley, A. M., Cabrera, A. V., Zhou, Z., van Wezel, G., Medema, M. H., Ganesan, C., Pao, A. C., Gombar, S., Dodd, D. 2023; 186 (16): 3400-3413.e20

  Abstract

  Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the disease gout. In most mammals, uric acid elimination is facilitated by the enzyme uricase. However, human uricase is a pseudogene, having been inactivated early in hominid evolution. Though it has long been known that uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here, we identify a widely distributed bacterial gene cluster that encodes a pathway for uric acid degradation. Stable isotope tracing demonstrates that gut bacteria metabolize uric acid to xanthine or short chain fatty acids. Ablation of the microbiota in uricase-deficient mice causes severe hyperuricemia, and anaerobe-targeted antibiotics increase the risk of gout in humans. These data reveal a role for the gut microbiota in uric acid excretion and highlight the potential for microbiome-targeted therapeutics in hyperuricemia.

  View details for DOI 10.1016/j.cell.2023.06.010

  View details for PubMedID 37541197

• Response to Alkali Administration in Women and Men With and Without CKD. Kidney medicine Pao, A. C., Shahzad, S. R., Song, S., Ganesan, C., Conti, S., Leppert, J., Cheung, A. K., Ix, J. H., Isakova, T., Wolf, M., Raj, D. S., Sprague, S. M., Fried, L. F., Gassman, J., Fong, P., Koike, S., Raphael, K. L. 2023; 5 (7): 100670

  View details for DOI 10.1016/j.xkme.2023.100670

  View details for PubMedID 37492113

  View details for PubMedCentralID PMC10363557

• 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

• 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

• 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

• Breaking the Cycle of Recurrent Calcium Stone Disease. Advances in kidney disease and health Malieckal, D. A., Ganesan, C., Mendez, D. A., Pao, A. C. 2023; 30 (2): 164-176

  Abstract

  Calcium stones are common and recurrent in nature, yet few therapeutic tools are available for secondary prevention. Personalized approaches for stone prevention have been informed by 24-hour urine testing to guide dietary and medical interventions. However, current evidence is conflicting about whether an approach guided by 24-hour urine testing is more effective than a generic one. The available medications for stone prevention, namely thiazide diuretics, alkali, and allopurinol, are not always prescribed consistently, dosed correctly, or tolerated well by patients. New treatments on the horizon hold the promise of preventing calcium oxalate stones by degrading oxalate in the gut, reprogramming the gut microbiome to reduce oxalate absorption, or knocking down expression of enzymes involved in hepatic oxalate production. New treatments are also needed to target Randall's plaque, the root cause of calcium stone formation.

  View details for DOI 10.1053/j.akdh.2022.12.004

  View details for PubMedID 36868731

• National Imaging Trends for Suspected Urinary Stone Disease in the Emergency Department. JAMA internal medicine Ganesan, C., Stedman, M. R., Liu, S., Conti, S. L., Chertow, G. M., Leppert, J. T., Pao, A. C. 2022

  View details for DOI 10.1001/jamainternmed.2022.4939

  View details for PubMedID 36315134

• Medical Treatment and Prevention of Urinary Stone Disease. The Urologic clinics of North America Spradling, K., Ganesan, C., Conti, S. 2022; 49 (2): 335-344

  Abstract

  The pathophysiology underlying urinary stone formation remains an area of active investigation. There are many pharmacotherapies aimed at optimizing metabolic factors and reducing urinary supersaturation of stone components that play an important role in urinary stone prevention. In addition, medical expulsive therapy for ureteral stones and medical dissolution therapy for uric acid-based urinary stones are helpful treatment tools and are used alongside surgical treatments in the management of urinary stones.

  View details for DOI 10.1016/j.ucl.2021.12.007

  View details for PubMedID 35428438

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

  Abstract

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

  View details for DOI 10.1210/clinem/dgac193

  View details for PubMedID 35363858

• Renal Morbidity Following Radical Cystectomy in Patients with Bladder Cancer. European urology open science Schmidt, B., Velaer, K. N., Thomas, I., Ganesan, C., Song, S., Pao, A. C., Thong, A. E., Liao, J. C., Chertow, G. M., Skinner, E. C., Leppert, J. T. 1800; 35: 29-36

  Abstract

  Background: Patients with chronic kidney disease (CKD) are poor candidates for standard treatments for muscle-invasive bladder cancer (MIBC) and may be more likely to experience adverse outcomes when diagnosed with MIBC.Objective: To investigate factors associated with the development of advanced CKD following radical cystectomy.Design setting and participants: Using national Veterans Health Administration utilization files, we identified 3360 patients who underwent radical cystectomy for MIBC between 2004 and 2018.Outcome measurements and statistical analysis: We examined factors associated with the development of advanced CKD (estimated glomerular filtration rate [eGFR] of <30 ml/min/1.73 m2) after radical cystectomy using multivariable logistic and proportional hazard regression, with and without consideration of competing risks. We examined survival using Kaplan-Meier product limit estimates and proportional hazard regression.Results and limitations: The median age at surgery was 67 yr and the mean preoperative eGFR was 69.1 ± 20.3 ml/min/1.73 m2. Approximately three out of ten patients (n = 962, 29%) progressed to advanced CKD within 12 mo. Older age (hazard ratio [HR] per 5-yr increase 1.15, 95% confidence interval [CI] 1.10-1.20), preoperative hydronephrosis (HR 1.50, 95% CI 1.29-1.76), adjuvant chemotherapy (HR 1.19, 95% CI 1.00-1.41), higher comorbidity index (HR 1.13, 95% CI 1.11-1.16 per point), and lower baseline kidney function (HR 0.75, 95% CI 0.73-0.78) were associated with the development of advanced CKD. Baseline kidney function at the time of surgery was associated with survival. Generalizability is limited due to the predominantly male cohort.Conclusions: Impaired kidney function at baseline is associated with progression to advanced CKD and mortality after radical cystectomy. Preoperative kidney function should be incorporated into risk stratification algorithms for patients undergoing radical cystectomy.Patient summary: Impaired kidney function at baseline is associated with progression to advanced chronic kidney disease and mortality after radical cystectomy.

  View details for DOI 10.1016/j.euros.2021.11.001

  View details for PubMedID 35024629

• Twenty-four-hour Urine Testing and Urinary Stone Disease Recurrence in Veterans UROLOGY Song, S., Thomas, I., Ganesan, C., Velaer, K. N., Chertow, G. M., Pao, A. C., Leppert, J. T. 2022; 159: 33-40

  View details for DOI 10.1016/j.urology.2021.10.005

  View details for Web of Science ID 000743888900008

• Urine oxalate and citrate excretion in patients with kidney stone disease: An ab initio clinical prediction. Physiological reports Ganesan, C., Pao, A. C. 2021; 9 (15): e14966

  View details for DOI 10.14814/phy2.14966

  View details for PubMedID 34337888

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

  Abstract

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

  View details for DOI 10.1016/j.eprac.2021.06.004

  View details for PubMedID 34126246

• Removing Race from eGFR calculations: Implications for Urologic Care. Urology Vilson, F. L., Schmidt, B., White, L., Soerensen, S. J., Ganesan, C., Pao, A. C., Enemchukwu, E., Chertow, G. M., Leppert, J. T. 2021

  Abstract

  Equations estimating the glomerular filtration rate are important clinical tools in detecting and managing kidney disease. Urologists extensively use these equations in clinical decision making. For example, the estimated glomerular function rate is used when considering the type of urinary diversion following cystectomy, selecting systemic chemotherapy in managing urologic cancers, and deciding the type of cross-sectional imaging in diagnosing or staging urologic conditions. However, these equations, while widely accepted, are imprecise and adjust for race which is a social, not a biologic construct. The recent killings of unarmed Black Americans in the US have amplified the discussion of racism in healthcare and has prompted institutions to reconsider the role of race in eGFR equations and raced-based medicine. Urologist should be aware of the consequences of removing race from these equations, potential alternatives, and how these changes may affect Black patients receiving urologic care.

  View details for DOI 10.1016/j.urology.2021.03.018

  View details for PubMedID 33798557

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

  Abstract

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

  View details for DOI 10.1002/jbmr.4260

  View details for PubMedID 33655611

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

  Abstract

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

  View details for DOI 10.1001/jamasurg.2020.2423

  View details for PubMedID 32725208

• The Urine Albumin-Creatinine Ratio and Kidney Function after Nephrectomy. The Journal of urology Sun, A. J., Thomas, I., Velaer, K. N., Ganesan, C., Song, S., Pao, A. C., Wagner, T. H., Brooks, J. D., Chertow, G. M., Leppert, J. T. 2020: 101097JU0000000000001005

  Abstract

  BACKGROUND: Patients with kidney cancer are at risk of developing chronic kidney disease (CKD) after radical and partial nephrectomy. We sought to determine if the urine albumin-creatinine ratio (UACR) is independently associated with progressive CKD after nephrectomy.METHODS: We performed a cohort study based within a large, integrated health care system. We identified patients who underwent radical or partial nephrectomy from 2004 to 2014 with UACR measured in the 12 months prior to surgery. We fit multivariable models to determine if the UACR was associated with the time to CKD progression (defined as reaching stage 4 or 5 CKD, eGFR <30 mL/min/1.73m2). We performed a parallel analysis measuring the time to stage 3b, 4 or 5 CKD (eGFR <45 mL/min/1.73m2) among patients with normal or near-normal preoperative kidney function (eGFR ≥60 mL/min/1.73 m2). We also examined the association between UACR and survival.RESULTS: 1930 patients underwent radical or partial nephrectomy and had preoperative UACR and pre- and post-operative eGFR. Of these, 658 (34%) and 157 (8%) had moderate (UACR 30-300mg/g) or severe albuminuria (UACR > 300mg/g), respectively. Albuminuria severity was independently associated with progressive CKD after radical (moderate albuminuria HR 1.7, 95%CI 1.4-2.2; severe albuminuria HR 2.3, 95%CI 1.7-3.1) and partial nephrectomy (moderate albuminuria HR 1.8, 95%CI 1.2-2.7; severe albuminuria HR 4.3, 95%CI 2.7-7.0). Albuminuria was also associated with survival following radical and partial nephrectomy.CONCLUSIONS: In patients undergoing radical or partial nephrectomy, the severity of albuminuria can stratify risk of progressive CKD.

  View details for DOI 10.1097/JU.0000000000001005

  View details for PubMedID 32125227

• Urinary Stone Disease in Pregnancy: A Claims-Based Analysis of 1.4 Million Patients. The Journal of urology Sohlberg, E. M., Brubaker, W. D., Zhang, C. A., Anderegg, L. D., Dallas, K., Song, S., Ganesan, C., Chertow, G., Pao, A., Liao, J., Leppert, J. T., Elliott, C. S., Conti, S. L. 2019: 101097JU0000000000000657

  Abstract

  PURPOSE: Urinary stone disease during pregnancy is poorly understood but is thought to be associated with increased maternal and fetal morbidity. We sought to determine the prevalence of urinary stone disease in pregnancy and whether urinary stone disease during pregnancy is associated with adverse pregnancy outcomes.MATERIALS AND METHODS: We identified all pregnant women from 2003 through 2017 in the Optum national insurance claims database. We used diagnosis claims to identify urinary stone disease and assess medical comorbidity. We established the prevalence of urinary stone disease during pregnancy, stratified by week of pregnancy. We further evaluated associations among urinary stone disease and maternal complications and pregnancy outcomes in both univariable and multivariable analyses.RESULTS: Urinary stone disease affects 8/1000 pregnancies and is more common in white women and women with more comorbid conditions. In fully adjusted models, pregnancies complicated by urinary stone disease had higher rates of adverse fetal outcomes, including prematurity and spontaneous abortions. This analysis is limited by its retrospective administrative claims design.CONCLUSIONS: The rate of urinary stone disease during pregnancy is higher than previously reported. Urinary stone disease is associated with adverse pregnancy outcomes.

  View details for DOI 10.1097/JU.0000000000000657

  View details for PubMedID 31738114

• Ultra-low-dose CT: An Effective Follow-up Imaging Modality for Ureterolithiasis. Journal of endourology Cheng, R. Z., Shkolyar, E., Chang, T. C., Spradling, K., Ganesan, C., Song, S., Pao, A. C., Leppert, J. T., Elliott, C. S., To'o, K., Conti, S. L. 2019

  Abstract

  BACKGROUND AND PURPOSE: Classically, abdominal X-ray (KUB), ultrasound or a combination of both have been routinely used for ureteral stone surveillance after initial diagnosis. More recently, ultra-low-dose CT (ULD CT) has emerged as a CT technique that reduces radiation dose while maintaining high sensitivity and specificity for urinary stone detection. We aim to evaluate our initial experience with ULD CT for patients with ureterolithiasis, measuring real-world radiation doses and stone detection performance.METHODS: We reviewed all ULD CT scans performed at the Veterans Affairs Palo Alto Health Care System between 2016 and 2018. We included patients with ureteral stones and calculated the mean effective radiation dose per scan. We determined stone location and size, if the stone was visible on the associated KUB or CT scout film, and if hydronephrosis was present. We performed logistic regression to identify variables associated with visibility on KUB or CT scout film and hydronephrosis.RESULTS: One-hundred and eighteen ULD scans were reviewed, of which 50 detected ureteral stones. The mean effective radiation dose was 1.04 ± 0.41 mSv. Of the ULD CTs that detected ureterolithiasis, 38% lacked visibility on KUB/CT scout film and had no associated hydronephrosis, suggesting they would be missed with a combination of KUB and ultrasound. Larger stones (OR: 1.40, 95% CI: 1.08-1.96 for every 1mm increase in stone size) were more likely to be detected by KUB/CT scout or ultrasound, while stones in the distal ureter (OR: 0.18, 95% CI: 0.03-0.81) were more likely to be missed by KUB/CT scout or hydronephrosis.CONCLUSION: Based on our institutions' initial experience with ULD CT, ULD CT detects small and distal ureteral stones that would likely be missed by KUB or ultrasound, while maintaining a low effective radiation dose. An ULD CT protocol should be considered when re-imaging for ureteral stones is necessary.

  View details for DOI 10.1089/end.2019.0574

  View details for PubMedID 31663371

• Spironolactone plus patiromer: proceed with caution LANCET Ganesan, C., Pao, A. C. 2019; 394 (10208): 1486–88

  View details for Web of Science ID 000493399500007

• Twenty-Four Hour Urine Testing and Prescriptions for Urinary Stone Disease-Related Medications in Veterans. Clinical journal of the American Society of Nephrology : CJASN Song, S. n., Thomas, I. C., Ganesan, C. n., Sohlberg, E. M., Chertow, G. M., Liao, J. C., Conti, S. n., Elliott, C. S., Pao, A. C., Leppert, J. T. 2019

  Abstract

  Current guidelines recommend 24-hour urine testing in the evaluation and treatment of persons with high-risk urinary stone disease. However, how much clinicians use information from 24-hour urine testing to guide secondary prevention strategies is unknown. We sought to determine the degree to which clinicians initiate or continue stone disease-related medications in response to 24-hour urine testing.We examined a national cohort of 130,489 patients with incident urinary stone disease in the Veterans Health Administration between 2007 and 2013 to determine whether prescription patterns for thiazide diuretics, alkali therapy, and allopurinol changed in response to 24-hour urine testing.Stone formers who completed 24-hour urine testing (n=17,303; 13%) were significantly more likely to be prescribed thiazide diuretics, alkali therapy, and allopurinol compared with those who did not complete a 24-hour urine test (n=113,186; 87%). Prescription of thiazide diuretics increased in patients with hypercalciuria (9% absolute increase if urine calcium 201-400 mg/d; 21% absolute increase if urine calcium >400 mg/d, P<0.001). Prescription of alkali therapy increased in patients with hypocitraturia (24% absolute increase if urine citrate 201-400 mg/d; 34% absolute increase if urine citrate ≤200 mg/d, P<0.001). Prescription of allopurinol increased in patients with hyperuricosuria (18% absolute increase if urine uric acid >800 mg/d, P<0.001). Patients who had visited both a urologist and a nephrologist within 6 months of 24-hour urine testing were more likely to have been prescribed stone-related medications than patients who visited one, the other, or neither.Clinicians adjust their treatment regimens in response to 24-hour urine testing by increasing the prescription of medications thought to reduce risk for urinary stone disease. Most patients who might benefit from targeted medications remain untreated.

  View details for DOI 10.2215/CJN.03580319

  View details for PubMedID 31712387

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

  Abstract

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

  View details for DOI 10.1371/journal.pone.0220768

  View details for PubMedID 31393935

• Regarding the possibility of anterior vascular injury from the posterior approach to the lumbar disc space: an anatomical study. Spine Ganesan, C., Petrus, L., Ross, I. B. 2012; 37 (22): E1371-5

  Abstract

  Anatomical study with magnetic resonance imaging data.To document the distances between the major retroperitoneal vessels and the anterior lumbar disc spaces; to determine the effect of patient positioning on these relationships; and to discuss ways to deal with vascular injury.It is well known that there are major vascular structures anterior to the lower lumbar spine. Vascular injury during posterior approaches, however, remains a problem. These anatomical relationships have not been determined in vivo, and there are no data on the effect of turning the patient prone, and onto bolsters.A random sampling of 49 women and 48 men was made. All examinations were performed in magnetic resonance scanners operating at 1.5 T. Measurements were made using electronic calipers on axial T2-weighted images. Post hoc studies were done on a smaller number of patients, to determine the effect of prone positioning.At the L4-L5 level, 66% of the common iliac arteries in women and 49% of those in men were within 5 mm of the anterior aspect of the disc space. At L5-S1, these numbers dropped to 23% for women and 19% for men. No relationship between the age of the patient and the distance from disc space to blood vessel was found. There was little change in these measurements between the supine and prone positions. The use of bolsters to decompress the abdominal contents in the prone position did not significantly alter the disc-artery distances. Venous relationships were also documented.The lower lumbar spine is confirmed to frequently be very close to the major retroperitoneal vessels. Turning the patient prone and placing the patient on bolsters does not change this relationship. This is part of the reason why vascular injuries may occur during routine lumbar spine surgery. Spine surgeons should be able to recognize and initiate treatment of such injuries.

  View details for DOI 10.1097/BRS.0b013e318267fb36

  View details for PubMedID 22781009