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Objective: To investigate the association of incident use of diuretics with subsequent risk of incident bone fractures., Patients and Methods: In a nationwide cohort of 863,339 US veterans receiving care from the VA health care system between October 1, 2004, and September 30, 2006, with follow-up through June 30, 2018, we examined the association of incident diuretic use (overall, and separately by thiazide, loop, and potassium-sparing diuretics) with subsequent risk of incident bone fractures using multivariable Cox regression models while minimizing confounding by indication using a target trial emulation approach., Results: Patients were 63.3±12.9 years old; 93.5% (n=807,180) were male; and 27.1% (n=233,996) were diabetic. Their baseline estimated glomerular filtration rate was 84.4±16.5 mL/min per 1.73 m 2 . Among 863,339 patients, 424,386 (49.2%) newly initiated diuretics, of which 77.4% (n=328,524), 22.5% (n=95,457), and 0.1% (n=405) were thiazide, loop, and potassium-sparing diuretic users, respectively. After multivariable adjustments, incident diuretic use (vs non-use) was significantly associated with higher risk of incident fracture (adjusted HR [aHR], 1.14; 95% CI, 1.11 to 1.16). The association was most pronounced for loop diuretics (aHR, 1.39; 95% CI, 1.35 to 1.44) but less evident for thiazide diuretics (aHR, 1.08; 95% CI, 1.06 to 1.10) and was not significant for potassium-sparing diuretics (aHR, 0.97; 95% CI, 0.62 to 1.52). The diuretic-fracture association was more evident in younger (vs older) patients, those with (vs without) corticosteroid use, and those with lower (vs higher) serum sodium levels., Conclusion: Incident use of diuretics, particularly loop diuretics, was independently associated with higher risk of incident bone fractures. Our findings suggest distinct pathophysiologic contributions of diuretics to bone metabolism and the need for careful attention to skeletal outcomes when initiating diuretics., (Published by Elsevier Inc.)

Context: Hypothyroidism is a common yet under-recognized condition in patients with chronic kidney disease (CKD), which may lead to end-organ complications if left untreated., Objective: We developed a prediction tool to identify CKD patients at risk for incident hypothyroidism., Methods: Among 15 642 patients with stages 4 to 5 CKD without evidence of pre-existing thyroid disease, we developed and validated a risk prediction tool for the development of incident hypothyroidism (defined as thyrotropin [TSH] > 5.0 mIU/L) using the Optum Labs Data Warehouse, which contains de-identified administrative claims, including medical and pharmacy claims and enrollment records for commercial and Medicare Advantage enrollees as well as electronic health record data. Patients were divided into a two-thirds development set and a one-third validation set. Prediction models were developed using Cox models to estimate probability of incident hypothyroidism., Results: There were 1650 (11%) cases of incident hypothyroidism during a median follow-up of 3.4 years. Characteristics associated with hypothyroidism included older age, White race, higher body mass index, low serum albumin, higher baseline TSH, hypertension, congestive heart failure, exposure to iodinated contrast via angiogram or computed tomography scan, and amiodarone use. Model discrimination was good with similar C-statistics in the development and validation datasets: 0.77 (95% CI 0.75-0.78) and 0.76 (95% CI 0.74-0.78), respectively. Model goodness-of-fit tests showed adequate fit in the overall cohort (P = .47) as well as in a subcohort of patients with stage 5 CKD (P = .33)., Conclusion: In a national cohort of CKD patients, we developed a clinical prediction tool identifying those at risk for incident hypothyroidism to inform prioritized screening, monitoring, and treatment in this population., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

BACKGROUND: Evidence from clinical trials shows that newer second-line diabetes medications-glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is)-have cardio-renal protective effects in addition to their glucose-lowering properties. Despite strong evidence of benefits, there is limited evidence regarding prescribing patterns for these medications, especially among populations at high risk for disparities. OBJECTIVE: To examine the associations of cardio-renal and obesity comorbidities and neighborhood factors with the prescribing of GLP-1RAs or SGLT2is in comparison with dipeptidyl peptidase 4 inhibitors (DPP-4is) or sulfonylureas (SFUs) and for each of the newer second-line diabetes medications (GLP-1RA vs DPP-4i, SGLT2i vs DPP-4i, GLP-1RA vs SFU, and SGLT2i vs SFU) in medically underserved populations. METHODS: A retrospective cohort study was conducted using electronic medical records from a health care delivery system that serves medically underserved populations in the Mid-South region of the United States. Metformin-treated adult patients with type 2 diabetes, and at least 1 prescription for GLP-1RA, SGLT2i, DPP-4i, or SFU class medications, were identified between April 2016 and August 2021. Neighborhood factors were assessed at the census tract level by geocoding and linking patient addresses to neighborhood-level risk factors. Using multilevel logistic regression models, we examined the associations of comorbidities and neighborhood factors with the prescription of newer second-line diabetes medications. RESULTS: 7,723 patients received newer second-line diabetes medications, with 16% prescribed GLP-1RAs, 11% prescribed SGLT2is, 28% prescribed DPP-4is, and 45% prescribed SFUs. Patients with cerebrovascular disease were significantly less likely to receive newer second-line diabetes medications (odds ratio [OR] = 0.65, 95% CI = 0.52-0.80). Patients with obesity were more likely to receive newer second-line diabetes medications (OR = 1.68, 95% CI = 1.48-1.90). Living in neighborhoods with higher proportions of college graduates was associated with a higher likelihood of receiving newer second-line diabetes medications (quartile 3 vs 1: OR = 1.30, 95% CI = 1.06-1.59; and quartile 4 vs 1: OR = 1.46, 95% CI = 1.13-1.88). CONCLUSIONS: Our findings demonstrate substantial underprescribing and significant clinical and neighborhood variations in the use of newer second-line diabetes medications. We found lower use of newer second-line diabetes medications among patients with cerebrovascular disease and higher use in those with obesity. Our findings also suggest that newer second-line diabetes medications are first adopted by those in higher socioeconomic groups, thus increasing disparities in care. DISCLOSURES: Dr Surbhi reports grants or contracts from the Tennessee Department of Health, Agency for Healthcare Research and Quality, and PhRMA Foundation. Dr Bailey reports honoraria from the SouthEast Texas Chapter of the American College of Healthcare Executives, leadership or fiduciary role in the Coalition for Better Health and The Healthy City, Inc., and stock or stock options in Proctor and Gamble, Walmart, and Apple. Dr Kovesdy reports personal fees from Bayer, Abbott, AstraZeneca, Takeda, Tricida, Akebia, Cara Therapeutics, Vifor, Rockwell, CSL Behring, Boehringer Ingelheim, and GSK, outside the submitted work. The other authors report no conflicts of interest.

Introduction: For patients with chronic kidney disease (CKD), the need for phosphate binder (PB) treatment peaks at onset of dialysis. This real-world study assessed rates of PB utilization and switching in patients with dialysis-dependent CKD (DD-CKD)., Methods: We identified patients with PB utilization among those with prevalent DD-CKD using 2018-2019 Medicare Parts A/B/D data. Patients were assigned to cohorts based on primary (most frequently used) PB among calcium acetate, ferric citrate, lanthanum carbonate, sevelamer (hydrochloride and carbonate), sucroferric oxyhydroxide. We measured proportion of patients who were adherent (proportion of days covered >80%) and persistent (patients whose last 90 days of outpatient dialysis reported PB use). Net switching rates were calculated as the difference between switches to and from the primary agent., Results: We identified 136,912 patients with PB use. Proportion of patients adherent ranged from 63.8% (lanthanum carbonate) to 67.7% (sevelamer) and persistent from 85.1% (calcium acetate) to 89.5% (ferric citrate). Most patients (73%) used the same PB throughout the study. Overall, 20.5% of patients experienced one switch and 2.3% two or more. Positive net switching rates were observed for ferric citrate, sucroferric oxyhydroxide, and lanthanum carbonate (2-10%) but negative for sevelamer and calcium acetate (-2% to -7%)., Conclusion: Adherence and persistence rates were low with slight variation across PBs. Net positive switching occurred for ferric citrate, sucroferric oxyhydroxide, and lanthanum carbonate. Further studies are needed to determine the reasons for these findings and could identify opportunities for better control of phosphate levels among patients with CKD., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Importance: Uric acid is a waste metabolite produced from the breakdown of purines, and elevated serum uric acid levels are associated with higher risk of hypertension, cardiovascular disease, and mortality and progression of chronic kidney disease (CKD). Treatment of hyperuricemia in patients with preexisting CKD has not been shown to improve kidney outcomes, but the associations of uric acid-lowering therapies with the development of new-onset kidney disease in patients with estimated glomerular filtration rate (eGFR) within reference range and no albuminuria is unclear., Objective: To examine the association of initiating uric acid-lowering therapy with the incidence of CKD., Design, Setting, and Participants: This cohort study included patients with eGFR of 60 mL/min/1.73 m2 or greater and no albuminuria treated at US Department of Veterans Affairs health care facilities from 2004 to 2019. Clinical trial emulation methods, including propensity score weighting, were used to minimize confounding. Data were analyzed from 2020 to 2022., Exposure: Newly started uric acid-lowering therapy., Main Outcomes and Measures: The main outcomes were incidences of eGFR less than 60 mL/min/1.73 m2, new-onset albuminuria, and end-stage kidney disease., Results: A total of 269 651 patients were assessed (mean [SD] age, 57.4 [12.5] years; 252 171 [94%] men). Among these, 29 501 patients (10.9%) started uric acid-lowering therapy, and 240 150 patients (89.1%) did not. Baseline characteristics, including serum uric acid level, were similar among treated and untreated patients after propensity score weighting. In the overall cohort, uric acid-lowering therapy was associated with higher risk of both incident eGFR less than 60 mL/min/1.73 m2 (weighted subhazard ratio [SHR], 1.15 [95% CI, 1.10-1.20; P < .001) and incident albuminuria (SHR, 1.05 [95% CI, 1.01-1.09; P < .001) but was not associated with the risk of end-stage kidney disease (SHR, 0.96 [95% CI, 0.62-1.50]; P = .87). In subgroup analyses, the association of uric acid-lowering therapy with worse kidney outcomes was limited to patients with baseline serum uric acid levels of 8 mg/dL or less., Conclusions and Relevance: These findings suggest that in patients with kidney function within reference range, uric acid-lowering therapy was not associated with beneficial kidney outcomes and may be associated with potential harm in patients with less severely elevated serum uric acid levels.

In the general population, elevated low-density lipoprotein (LDL) cholesterol levels are an important risk factor for cardiovascular disease (CVD) and mortality; however, the association of LDL with mortality risk and cardiovascular events are less clear in chronic kidney disease (CKD). We sought to examine the relationship of LDL with mortality and rates of atherosclerotic cardiovascular disease (ASCVD) and non-atherosclerotic cardiovascular-related (non-ASCVD) hospitalizations across CKD stages. Our analytical cohort consisted of 1,972,851 United States veterans with serum LDL data between 2004 and 2006. Associations of LDL with all-cause and cardiovascular mortality across CKD stages were evaluated using Cox proportional hazard models with adjustment for demographics, comorbid conditions, smoking status, prescription of statins and non-statin lipid-lowering drugs, body mass index, albumin, high-density lipoprotein, and triglycerides. Associations between LDL and ASCVD and non-ASCVD hospitalizations were estimated using negative binomial regression models across CKD stages. The cohort consisted of 5% female, 14% Black, 29% diabetic, 33% statin-users, and 44% current smokers, with a mean patient age of 64 ± 14 years. Patients with high LDL (≥160 mg/dL) had a higher risk of all-cause and cardiovascular mortality as well as ASCVD and non-ASCVD hospitalization rates across all CKD stages compared with the reference (LDL 70 to <100 mg/dL). The associations with all-cause and cardiovascular mortality and ASCVD hospitalization rate were attenuated at higher CKD stages. These trends were reversed with amplification of the association of high LDL with non-ASCVD hospitalization at higher CKD stages. In conclusion, associations of LDL with mortality and both ASCVD and non-ASCVD hospitalizations are modified according to kidney disease stage., (Published by Elsevier Inc.)

Background High triglycerides are associated with atherosclerotic cardiovascular disease (ASCVD) risks. Among patients with advanced chronic kidney disease (CKD), the association of elevated triglycerides with mortality is diminished and, thus, we investigated the relationship of triglycerides with ASCVD and non-ASCVD hospitalizations across CKD stages. Methods and Results The cohort comprised 2 963 176 veterans who received care in 2004 to 2006 (baseline) and were followed up to 2014. Using Cox models, we evaluated baseline and time-varying triglycerides with time to ASCVD or non-ASCVD hospitalizations, stratified by baseline CKD stage, and adjusted for demographics and baseline or time-updated clinical characteristics. The cohort mean±SD age was 63±14 years, with a baseline median (interquartile range) triglycerides level of 127 (87-189) mg/dL, and a quarter had prevalent CKD. There was a linear association between baseline triglycerides and ASCVD risk; however, the risk with high triglycerides ≥240 mg/dL attenuated with worsening CKD stages (reference: triglycerides 120 to <160 mg/dL). Baseline triglycerides were associated with a U-shaped relationship for non-ASCVD events in patients with CKD 3A to 3B. Patients with late-stage CKD had lower to null relationships between baseline triglycerides and non-ASCVD events. Time-varying triglycerides associations with ASCVD were similar to baseline analyses. Yet, the time-varying triglycerides relationship with non-ASCVD events was inverse and linear, where elevated triglycerides were associated with lower risks. Conclusions Associations of higher triglycerides with ASCVD and non-ASCVD events declined across advancing CKD stages, where a lower to null risk was observed in patients with advanced CKD. Studies are needed to examine the impact of advanced CKD on triglycerides metabolism and its association with outcomes in this high-risk population.

BACKGROUND: Patients with advanced chronic kidney disease (CKD) are at high risk for dyskalemias, which may induce arrhythmias that require immediate emergent or hospital care. The association of dyskalemias with short-term hospital/emergency room (ER) visits in advanced CKD is understudied. OBJECTIVE: To assess the association of dyskalemias with short-term hospital/ER visits in an advanced CKD population. METHODS: From among 102,477 US veterans transitioning to dialysis from 2007 to 2015, we identified 21,366 patients with 2 predialysis outpatient eGFR < 30 ml/min/1.73m 2 90-365 days apart (with the second eGFR serving as the index date) and at least 1 potassium (K) in the baseline period (1 year before index) and 1 outpatient K (oK) in the follow-up (1 year after the index but before dialysis initiation). We examined the association of time-varying hypokalemia (K < 3.5 mEq/L) and hyperkalemia (K > 5.5 mEq/L) vs referent (3.5-5.5 mEq/L) with separate hospital and ER visits within 2 calendar days following each oK value over the 1-year follow-up period from the index. We used generalized estimating equations with binary distribution and logit link to model the exposure-outcome relationship adjusted for various confounders. We conducted various subgroup and sensitivity analyses to test the robustness of our results. RESULTS: Over the 1-year follow-up, 125,266 oK measurements were observed, of which 6.8% and 3.7% were classified as hyper- and hypokalemia, respectively. In the multivariable-adjusted model, hyperkalemia (adjusted odds ratio [aOR] = 2.04; 95% CI = 1.88-2.21) and hypokalemia (aOR = 1.66; 95% CI = 1.48-1.86) were associated with significantly higher odds of hospital visits. Similarly, hyperkalemia (aOR = 1.83; 95% CI = 1.65-2.03) and hypokalemia (aOR = 1.24; 95% CI = 1.07-1.44) were associated with significantly higher odds of ER visits. Results were robust to subgroups and sensitivity analyses. CONCLUSIONS: In patients with advanced CKD, dyskalemias are associated with higher risk of hospital/ER visits. Interventions targeted at lowering the risk of dyskalemias might help in reducing the health care utilization and associated economic burden among patients with advanced CKD experiencing dyskalemias. DISCLOSURES: This study was supported by grant 5U01DK102163 from the National Institute of Health (NIH) to Kamyar Kalantar-Zadeh and Csaba P. Kovesdy and by resources from the US Department of Veterans Affairs. The data reported here have been supplied in part by the United States Renal Data System (USRDS). Support for VA/CMS data were provided by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development, VA Information Resource Center (project numbers SDR 02-237 and 98-004). Opinions expressed in this article are those of the authors and do not necessarily represent the opinion of the Department of Veterans Affairs or the funding institution. Kovesdy has received honoraria from Akebia, Ardelyx, Astra Zeneca, Bayer, Boehringer-Ingelheim, Cara Therapeutics, Reata, and Tricida unrelated to this study. Kalantar-Zadeh has received honoraria and/or support from Abbott, Abbvie, ACI Clinical (Cara Therapeutics), Akebia, Alexion, Amgen, American Society of Nephrology, Astra-Zeneca, Aveo, BBraun, Chugai, Cytokinetics, Daiichi, DaVita, Fresenius, Genentech, Haymarket Media, Hofstra Medical School, International Federation of Kidney Foundations, International Society of Hemodialysis, International Society of Renal Nutrition & Metabolism, Japanese Society of Dialysis Therapy, Hospira, Kabi, Keryx, Kissei, Novartis, OPKO, National Institutes of Health, National Kidney Foundations, Pfizer, Regulus, Relypsa, Resverlogix, Dr Schaer, Sandoz, Sanofi, Shire, Veterans Affairs, Vifor, UpToDate, and ZS-Pharma, unrelated to this study. Gatwood has received research support from AstraZeneca, Merck & Co., and GlaxoSmithKline unrelated to this study. Obi has received research support from Relypsa/Vifor Pharma Inc. The remaining authors declare that they have no relevant financial interests.

Background: High-protein diets (e.g., Paleo, Atkins, South Beach, ketogenic) have gained popularity as a means to promote weight loss and avoid excess carbohydrate consumption. Yet in chronic kidney disease (CKD) patients, evidence suggests low dietary protein intake (DPI) leads to attenuation of kidney function decline, although concerns remain for risk of protein-energy wasting., Objectives: To examine associations of DPI with mortality in a nationally representative cohort of US adults, stratified by kidney function., Methods: We examined the association between daily DPI scaled to actual body weight (ABW), ascertained by 24-h dietary recall, with all-cause mortality among 27,604 continuous NHANES adult participants (1999-2010), stratified according to impaired versus normal kidney function (estimated glomerular filtration rates <60 compared with ≥60 ml/min/1.72 m2, respectively), using multivariable Cox models. We also examined the relation between high biological value (HBV) protein consumption with mortality., Results: In participants with impaired kidney function, a high DPI of ≥1.4 g/kg ABW/day was associated with higher mortality, while lower DPI levels were not associated with mortality (reference, 0.6 to <1.0 g/kg ABW/day): the adjusted HRs (aHRs) were 1.09 (95% CI: 0.90, 1.32), 1.03 (95% CI: 0.82, 1.29), and 1.37 (95% CI: 1.02, 1.85) for DPI <0.6, 1.0 to <1.4, and ≥1.4 g/kg ABW/day, respectively. Yet in participants with normal kidney function, a low DPI of <0.6 g/kg ABW/day was associated with higher mortality, whereas higher DPI levels were not associated with death: the aHRs were 1.18 (95% CI: 1.04, 1.34), 0.92 (95% CI: 0.81, 1.04), and 0.99 (95% CI: 0.85, 1.16) for DPI <0.6, 1.0 to <1.4, and ≥1.4 g/kg ABW/day, respectively. The highest 2 tertiles of HBV consumption were associated with higher mortality in participants with impaired kidney function., Conclusions: Among participants with impaired kidney function, a higher DPI and greater HBV consumption were associated with higher mortality, whereas a lower DPI was associated with higher mortality in those with normal kidney function. Further studies are needed to elucidate the specific pathways between higher DPI and mortality in CKD., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objectives: To assess the relationship between relative estimated glomerular filtration rate (eGFR) change and outcomes in patients with type 2 diabetes (T2D)., Study Design: This retrospective cohort study utilized administrative claims (Humana Research Database) for patients with T2D aged 65 to 89 years, enrolled in a Medicare Advantage plan, with an initial eGFR of 25 to 89 mL/min/1.73m2 in 2008 to 2017, and a second eGFR measurement within 3 to 24 months after the identification date., Methods: The primary exposure was relative decline in eGFR of 40% or more in a 2-year period. Outcomes included end-stage kidney disease (ESKD) or kidney failure, a composite cardiovascular (CV) outcome, and all-cause mortality assessed with multivariable adjusted survival models. Days out of the home and all-cause total costs were assessed using multivariable adjusted generalized linear models., Results: A total of 288,170 patients were included. The adjusted HR for ESKD or kidney failure was 4.38 (95% CI, 3.99-4.81) in patients with 40% or greater decline versus those with a decline of less than 40%. The adjusted HR was 1.67 (95% CI, 1.53-1.82) for the composite CV outcome and 1.98 (95% CI, 1.87-2.10) for all-cause mortality. Patients with a 40% or greater relative decline had 2.23 times higher all-cause total per patient per month costs ($1910 difference) and 1.82 times higher odds of 7 or more days out of the home versus those with less than 40% relative eGFR decline., Conclusions: Our results indicate that a relative eGFR decline of 40% or greater is associated with an increased risk of ESKD or kidney failure, CV outcomes and all-cause mortality, and increased health care resource utilization and costs.

BACKGROUND: ICD-10-CM codes exist that facilitate provider designation of patients as "nonadherent to therapy"; however, it is unclear whether this label accurately reflects patient behavior according to widely accepted medication adherence metrics using pharmacy claims data. OBJECTIVE: To determine the extent to which patients are accurately coded for and have calculated rates of nonadherence using ICD-10-CM codes and claims, respectively. METHODS: This was a retrospective cohort study using commercial insurance and Medicare Advantage claims data from 2015 to 2016. The analysis focused on adults aged 18 years and older who had been diagnosed with and were being treated for hypertension and/or diabetes and had been coded as nonadherent by a provider during an outpatient encounter. Adherence (proportion of days covered [PDC]) to oral antihypertensive and/or antidiabetic therapy was calculated 6 months before and after the first nonadherence diagnosis identified in outpatient encounters, using 2 distinct calculation methods. Inferential statistics and multivariable logistic regression were used to determine predictors of coding agreement and changes in adherence after the nonadherence diagnosis controlling for available patient characteristics. RESULTS: A total of 1,142 patients who had been coded as nonadherent were identified, of which between 5.3% and 22.0% (depending on metric and condition) had PDCs before the nonadherence code deeming them adherent according to claims, conflicting with nonadherence diagnosis codes documented by their providers. Mean PDCs increased significantly (20.5%-24.3%, all P < 0.001) among both conditions following the nonadherent code, as did the proportion adherent (PDC > 80%), irrespective of disease (all P < 0.01). The odds of being correctly labeled nonadherent according to claims decreased with age (diabetes odds ratio [OR]: 0.82, 95% CI = 0.694-0.976; hypertension OR: 0.86, 95% CI = 0.773-0.944) but were higher among those taking more medications (diabetes OR: 2.97, 95% CI = 1.658-5.326; hypertension OR: 3.0, 95% CI = 2.095-4.305). Following the nonadherence coding, the odds of being adherent increased with age in both models (diabetes OR: 1.17, 95% CI = 1.012-1.363; hypertension OR: 1.13, 95% CI = 1.048-1.223) yet decreased with increasing medications (diabetes OR: 0.25, 95% CI = 0.138-0.468; hypertension OR: 0.47, 95% CI = 0.368-0.592) and were lower if the patient was observed to be nonadherent before the index encounter (diabetes OR: 0.33, 95% CI = 0.146-0.760; hypertension OR: 0.25, 95% CI = 0.152-0.423). CONCLUSIONS: In general, providers are properly classifying patients as nonadherent using ICD-10-CM codes, but additional assessment is needed to determine the reasons for the remaining mismatch between claims- and diagnosis-based nonadherence. In addition, the correct claims-based metric needs to be established to improve alignment with provider interpretation of patient medication use. DISCLOSURES: No outside funding supported this study. Gatwood reports grants from GlaxoSmithKline, Merck & Co., and AstraZeneca, outside the submitted work. Kovesdy reports consulting fees from Amgen, Sanofi, Fresenius Medical Care, Keryx, Bayer, Abbott, Abbvie, Dr. Schar, Astra-Zeneca, Takeda, Tricida, and Reata and grants from Shire, outside the submitted work. The other authors have nothing to disclose. Findings described in this article were presented as a poster at the American College of Clinical Pharmacy Annual Meeting in New York City, October 2019.

Objective: To examine the screening rates for kidney damage and function among patients with type 2 diabetes (T2D) and chronic kidney disease stage at diabetes diagnosis using a US administrative claims database., Patients and Methods: This cohort study used a claims database enriched with laboratory results data. Patients with T2D (defined as 1 inpatient or 2 outpatient claims for diabetes), aged 18 years or older, and with at least 1 year of follow-up enrollment were identified. Patients with type 1 diabetes, kidney disease, or other related conditions at baseline were excluded. We estimated screening rates using laboratory orders for serum creatinine and estimated glomerular filtration rate (eGFR) measurement and urine albumin to creatinine ratio (UACR). Chronic kidney disease severity was reported using the Kidney Disease: Improving Global Outcomes classification based on laboratory results., Results: A total of 1,881,447 patients with T2D were eligible for analysis. Mean ± SD age was 63.1±13.1 years; 947,150 patients (50.3%) were male. Serum creatinine tests were ordered within 14 days of the index date among 290,722 patients of 622,915 (46.7%) patients with newly-recognized T2D. Overall, 1,595,964 patients (84.8%) had at least one serum creatinine test ordered during the 1-year follow-up period. Fewer patients received a UACR test during follow-up (814,897 [43.3%]). Less than half of all patients with T2D received a laboratory test order for both serum creatinine and urine albumin measurements during the follow-up period., Conclusion: Physicians treating patients with diabetes are selectively adhering to chronic kidney disease screening guidelines, as indicated by high rates of eGFR testing, but less frequent UACR testing. Despite recommendations to monitor both eGFR and UACR, less than half of patients were screened for albuminuria during the 1-year follow-up., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) is among the most prevalent and dire complications of diabetes mellitus in adults across the world. Diabetes substantially contributes to the burden of kidney disease, such that one third to one half of CKD in the United States and many other countries is attributable to diabetic kidney disease (DKD). As DKD progresses to end-stage renal disease (ESRD), patients are at heightened risk for atypical glycemic complications, including the development of burnt-out diabetes, manifested by hypoglycemic bouts and poor outcomes. Furthermore, even in the absence of diabetes, hypoglycemia is a frequent occurrence in CKD patients that may contribute to their high burden of cardiovascular disease and death. Extrapolation of data from clinical trials in high-cardiovascular-risk populations and observational studies in patients with non-dialysis-dependent (NDD) CKD and ESRD suggest that moderate glycemic targets defined by glycated hemoglobin levels of 6% to 8% and glucose levels of 100 to 150 mg/dL are associated with better survival in DKD patients. However, given the imprecision of glycated hemoglobin levels in kidney disease, further research is needed to determine the optimal glycemic metric and target in diabetic NDD-CKD and ESRD patients. Given their exceedingly high cardiovascular morbidity and mortality, there is a compelling need for further investigation of how to optimally manage dysglycemia in the NDD-CKD and ESRD populations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: CKD, a common complication of type-2 diabetes (T2D), causes considerable disease burden. Patients with T2D and CKD are considered high-risk for complications; however, studies describing patients with T2D and incident CKD identified from real-world data using the diagnostic gold-standard criteria - estimated glomerular filtration rate and urine albumin-to-creatinine ratio (UACR) - are scarce., Methods: In this population-based cohort study, we sought to estimate the rates of cardiovascular and renal outcomes among patients with T2D and CKD by comorbidity subgroups and CKD severity. Patients were sampled between 2008 and 2017 from de-identified US administrative claims enriched with laboratory data. Analyses were stratified by prevalent heart failure (HF), anemia, and resistant hypertension and the KDIGO categories at index., Results: We identified 106,369 patients with T2D and incident CKD. The rate of all-cause hospitalization was 189 [95% CI: 187, 191] per 1,000 person-years with cardiovascular-related hospitalizations being more frequent than kidney-related outcomes. The rate of acute kidney failure was 77.3 [95% CI: 76.2, 78.5] per 1,000 person-years. Patients with HF experienced a 4-times higher rate for cardiovascular events compared to those without. Rates of hospitalization increased from 5- to 6-fold with increasing KDIGO severity., Conclusions: Multimorbidity and advance stages of CKD increase the risk of cardiovascular and renal complications among patients with T2D diabetes. Earlier CKD diagnosis as well as interventions and coordinated care addressing other comorbid conditions present at diagnosis may reduce the overall disease burden in this population., (© 2021 S. Karger AG, Basel.)

Introduction: Patients with advanced non-dialysis-dependent CKD (NDD-CKD) have a reduced ability for maintaining plasma potassium (K) in normal range. Deviation from normal plasma K ranges is associated with increased mortality; however, the average trajectory of plasma K over time in patients with advanced NDD-CKD and the outcomes associated with plasma K trajectory are unknown., Methods: We identified 34,167 US veterans with advanced NDD-CKD transitioning to dialysis between October 2007 and March 2015 with at least 1 K measurement each year over a 3-year period prior to dialysis transition (3-year prelude). The K trajectory defined as the change in K (slope) per year over the entire 3-year prelude was estimated using linear mixed-effects models. The association between unadjusted (crude) K slope (categorized as stable [-0.09 to 0.09 mEq/L/year], decreasing [≤-0.10 mEq/L/year], and increasing [≥0.10 mEq/L/year]) and time to all-cause and cardiovascular mortality during the 6 months following dialysis initiation was assessed using multivariable-adjusted survival models., Results: The crude and multivariable-adjusted K slopes (mean, 95% CI) over the 3-year prelude were 0.008 (0.0059, 0.0110) and -0.15 mEq/L/year (-0.19, -0.11), respectively. Decreasing K slope was associated with higher multivariable-adjusted risk of all-cause mortality (adjusted hazard ratio [95% CI] vs. stable K slope: 1.08 [1.00-1.17]). No association was observed between K slope and cardiovascular mortality., Discussion/conclusion: The average intraindividual plasma K trajectory is remarkably stable in patients with advanced NDD-CKD. A decreasing K slope is associated with higher all-cause mortality risk., (© 2021 S. Karger AG, Basel.)

Introduction: Hypo- and hyperkalemia are associated with a higher risk of ischemic stroke. However, this association has not been examined in an advanced chronic kidney disease (CKD) population., Methods: From among 102,477 US veterans transitioning to dialysis between 2007 and 2015, 21,357 patients with 2 pre-dialysis outpatient estimated glomerular filtration rates <30 mL/min/1.73 m2 90-365 days apart and at least 1 potassium (K) each in the baseline and follow-up period were identified. We separately examined the association of both baseline time-averaged K (chronic exposure) and time-updated K (acute exposure) treated as categorized (hypokalemia [K <3.5 mEq/L] and hyperkalemia [K >5.5 mEq/L] vs. referent [3.5-5.5 mEq/L]) and continuous exposure with time to the first ischemic stroke event prior to dialysis initiation using multivariable-adjusted Cox regression models., Results: A total of 2,638 (12.4%) ischemic stroke events (crude event rate 41.9 per 1,000 patient years; 95% confidence interval [CI] 40.4-43.6) over a median (Q1-Q3) follow-up time of 2.56 (1.59-3.89) years were observed. The baseline time-averaged K category of hypokalemia (adjusted hazard ratio [aHR], 95% CI: 1.35, 1.01-1.81) was marginally associated with a significantly higher risk of ischemic stroke. However, time-updated hyperkalemia was associated with a significantly lower risk of ischemic stroke (aHR, 95% CI: 0.82, 0.68-0.98). The exposure-outcome relationship remained consistent when using continuous K levels for both the exposures., Discussion/conclusion: In patients with advanced CKD, hypokalemia (chronic exposure) was associated with a higher risk of ischemic stroke, whereas hyperkalemia (acute exposure) was associated with a lower risk of ischemic stroke. Further studies in this population are needed to explore the mechanisms underlying these associations., (© 2021 S. Karger AG, Basel.)

BACKGROUND: Chronic kidney disease (CKD) is one of the most common complications of type 2 diabetes mellitus (T2D) and results in considerable economic burden. Current studies describing cost and health care resource utilization (HCRU) in T2D patients with CKD in real-world data are few. Even more scarce is evidence that takes into account disease severity and other comorbidities. OBJECTIVES: To (a) describe T2D patients with CKD identified in U.S. administrative claims data using laboratory test results for kidney function that are considered the gold standard criteria for kidney disease diagnosis and (b) estimate the annual HCRU and costs among these patients, overall and by disease severity and comorbidity subgroup. METHODS: Optum CDM data between the years 2008 and 2017 were used to identify T2D patients with newly recognized CKD, using laboratory test results for estimated glomerular filtration rate (eGFR) or urine albumin-to-creatinine ratio (UACR). The study estimated annualized total, inpatient, outpatient, and pharmacy costs and the number of outpatient, inpatient, and emergency room visits in the first year after CKD identification. Analyses were stratified by prevalent anemia, heart failure (HF), resistant hypertension, and by CKD stages. RESULTS: T2D patients with newly recognized CKD (n = 106,369) had a high prevalence of cardiovascular comorbidities and incurred on average $24,029 of total cost per person per year in the first year after CKD identification. Patients with HF and anemia incurred on average $41,951 and $31,127 of total annual cost, respectively. Patients identified at stage 5 CKD incurred on average $110,210 of total annual cost and had roughly a 7-fold higher annual inpatient hospitalization rate compared with patients identified at stage 1 CKD. CONCLUSIONS: Administrative claims data linked to laboratory results provide an opportunity to identify CKD patients using the gold standard criteria from clinical practice, minimizing potential misclassification of patients. Identified CKD patients, particularly those with HF, anemia, and more advanced CKD stage, incur high HCRU and cost. Better monitoring, earlier CKD diagnosis, and interventions that are effective in halting or slowing the progression of CKD, as well as at managing comorbid conditions, could be effective means to reduce the economic burden of CKD in T2D. DISCLOSURES: This study was funded by Bayer. Kelly is an employee of, and owns stock options in, Aetion, which was contracted by Bayer to conduct the study. Petruski-Ivleva was an employee of Aetion during the planning, analysis, and interpretation stages of the study. Kovesdy received honoraria from Amgen, Astra Zeneca, Bayer, Cara Therapeutics, Reata, Takeda, and Tricida. Fried received consultant fees from Bayer, Novo Nordisk, and Bristol-Meyers Squibb. Folkerts, Blankenburg, and Gay are Bayer employees. This work was presented as a poster at the annual European Association for the Study of Diabetes (EASD) conference held in Barcelona, Spain, on September 16-20, 2019.

National data on patient characteristics, treatment, and outcomes of critically ill coronavirus disease 2019 (COVID-19) solid organ transplant (SOT) patients are limited. We analyzed data from a multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units (ICUs) at 68 hospitals across the United States from March 4 to May 8, 2020. From 4153 patients, we created a propensity score matched cohort of 386 patients, including 98 SOT patients and 288 non-SOT patients. We used a binomial generalized linear model (log-binomial model) to examine the association of SOT status with death and other clinical outcomes. Among the 386 patients, the median age was 60 years, 72% were male, and 41% were black. Death within 28 days of ICU admission was similar in SOT and non-SOT patients (40% and 43%, respectively; relative risk [RR] 0.92; 95% confidence interval [CI]: 0.70-1.22). Other outcomes and requirement for organ support including receipt of mechanical ventilation, development of acute respiratory distress syndrome, and receipt of vasopressors were also similar between groups. There was a trend toward higher risk of acute kidney injury requiring renal replacement therapy in SOT vs. non-SOT patients (37% vs. 27%; RR [95% CI]: 1.34 [0.97-1.85]). Death and organ support requirement were similar between SOT and non-SOT critically ill patients with COVID-19., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Deceased-donor kidney transplantation (KT) from hepatitis C (HCV)-infected donors into HCV-uninfected recipients (HCV D+/R-) could become standard care in the near future. However, HCV viral replication by viral transmission might lead to a higher incidence of cytomegalovirus (CMV) infection in these recipients., Methods: A national-registry-based retrospective cohort study was conducted using the Scientific Registry of Transplant Recipients (SRTR) data set. We assessed the incidence of CMV infection in HCV antibody (Ab) negative recipients receiving kidneys from HCV Ab positive (HCVAb D+/R-) and negative (HCVAb D-/R-) donors. The risk of CMV infection was analyzed by Cox regression analysis in a propensity score (PS) matched-cohort of HCVAb D+/R- ( n  = 950) versus HCVAb D-/R- ( n  = 950). Sensitivity analysis was also conducted in the entire cohort ( n  = 181 082)., Results: The mean age at baseline was 54 years, 75% were male, and 55% of the patients were African American in PS-matched cohort. Compared to the HCVAb D-/R - patients, recipients with HCVAb D+/R - showed identical probability for the incidence of CMV infection (Hazard Ratio (HR) = 1.00, 95% Confidence Interval (CI): 0.82-1.22). In the sensitivity analysis, compared to the HCVAb D-/R - patients, the HCVAb D+/R - group had a significantly lower risk of CMV infection in the unadjusted analysis (HR = 0.75, 95%CI: 0.65-0.85), while this risk difference disappeared after the adjusted analysis (HR = 0.99, 95%CI: 0.87-1.14)., Conclusion: The incidence of CMV infection was similar in recipients who received HCVAb D + and HCVAb D - KT. Further studies are needed to assess this association in KT from HCV nucleic acid positive donors.

Background: Eosinophils are traditionally known as moderators of allergic reactions; however, they have now emerged as one of the principal immune-regulating cells as well as predictors of vascular disease and mortality in the general population. Although eosinophilia has been demonstrated in hemodialysis (HD) patients, associations of eosinophil count (EOC) and its changes with mortality in HD patients are still unknown., Methods: In 107 506 incident HD patients treated by a large dialysis organization during 2007-11, we examined the relationships of baseline and time-varying EOC and its changes (ΔEOC) over the first 3 months with all-cause mortality using Cox proportional hazards models with three levels of hierarchical adjustment., Results: Baseline median EOC was 231 (interquartile range 155-339) cells/μL and eosinophilia (>350 cells/μL) was observed in 23.4% of patients. There was a gradual increase in EOC over time after HD initiation with a median ΔEOC of 5.1 (IQR -53-199) cells/μL, which did not parallel the changes in white blood cell count. In fully adjusted models, mortality risk was highest in subjects with lower baseline and time-varying EOC (<100 cells/μL) and was also slightly higher in patients with higher levels (≥550 cells/μL), resulting in a reverse J-shaped relationship. The relationship of ΔEOC with all-cause mortality risk was also a reverse J-shape where both an increase and decrease exhibited a higher mortality risk., Conclusions: Both lower and higher EOCs and changes in EOC over the first 3 months after HD initiation were associated with higher all-cause mortality in incident HD patients., (Published by Oxford University Press on behalf of ERA-EDTA 2020. This work is written by US Government employees and is in the public domain in the US.)

Background: Adherence to prescribed medications is connected with, but is not a guarantee of, improved disease management and health outcomes. It remains unclear whether underlying health disparities exist among patients adherent to therapy and whether differences in outcomes vary by race and residential areas of the country., Objective: To determine the extent of racial and regional variation in outcomes within 5 years of oral antidiabetic drug initiation among veterans adherent to therapy., Design: Retrospective cohort study of 83,265 US Veterans Health Administration data, 2002-2014 PATIENTS: US veterans with uncomplicated diabetes and taking oral antidiabetic agents MAIN MEASURES: Veterans initially adherent to oral antidiabetic therapy were followed for up to 5 years, and comparisons focused on differences between non-Hispanic White and non-Hispanic Black veterans across geographic region and residential type (urban or rural). Outcomes included composite cardiovascular events, composite cerebrovascular events, or all-cause mortality using Poisson and adjusted Cox proportional hazards models., Key Results: Cardiovascular event and all-cause mortality rates differed by race and region, while urban/rural differences were evident for cerebrovascular events and all-cause mortality. For non-Hispanic Blacks, the mortality rate was half that compared to non-Hispanic Whites (6.5 [95% CI 5.8-7.2] versus 13.3 [95% CI 12.9-13.8], p < 0.0001). Compared to the Northeast, all other regions had higher adjusted hazards for cardiovascular or cerebrovascular events (with a single exception), but no regional differences in all-cause mortality were observed. Models with interactions demonstrated that racial differences in cardiovascular events and all-cause mortality were isolated to the Midwest (HR 1.99 [95% CI 1.301-3.06; HR 1.64 [95% CI 1.210-2.215]) and South (HR 1.69 [85% CI 1.347-2.131]; HR 1.27 [95% CI 1.095-1.470])., Conclusions: Despite adherence to therapy, differences in outcomes are likely among veterans with diabetes based on race and geography. Localized analyses may uncover specific social determinants contributing to differences in outcomes.

Objective : Patiromer is a sodium-free, non-absorbed, potassium (K + ) binder approved for the treatment of hyperkalemia (HK). Among US Veterans with HK, this retrospective, observational cohort study evaluated patiromer utilization, RAASi continuation, and K + concentration change following patiromer initiation. Methods : Using data from the Veterans Affairs Corporate Data Warehouse, Veterans with HK (K + ≥5.1 mmol/L) were included upon patiromer initiation (index date) during the study period (1/2016-8/2018). All patients had heart failure (HF), diabetes, or chronic kidney disease (CKD). Patients with end-stage renal disease were excluded. The following outcomes were assessed within 6-months post-patiromer initiation: patiromer utilization (using proportion of days covered); K + concentration change (pre- vs post-initiation); and RAASi continuation. Results : 288 Veterans with HK were included. Baseline characteristics were: median age 70 years, African-American race 24%, diabetes 83%, HF 32%, CKD 95%, and median K + concentration 5.7 mmol/L. At 1, 3, and 6 months post-index, the median patiromer PDC was 100%, 66%, and 44%, respectively. K + concentration reductions post-patiromer initiation were, on average, - 1.0 mmol/L ( P < 0.001). At 3-6 months, 71% of patiromer initiators had K + <5.1 mmol/L and 95% had K + <5.5 mmol/L. RAASi therapy was continued in >80%-90% of patiromer-treated patients. Conclusions : The real-world utilization results suggest patiromer is used for the chronic management of HK. Clinically relevant K + concentration reductions were observed at all study time points. The successful management of HK may have contributed to the observed high rate of RAASi therapy continuation. Further research is warranted to corroborate and extend these findings.

Anemia is a complication that affects a majority of individuals with advanced CKD. Although relative deficiency of erythropoietin production is the major driver of anemia in CKD, iron deficiency stands out among the mechanisms contributing to the impaired erythropoiesis in the setting of reduced kidney function. Iron deficiency plays a significant role in anemia in CKD. This may be due to a true paucity of iron stores (absolute iron deficiency) or a relative (functional) deficiency which prevents the use of available iron stores. Several risk factors contribute to absolute and functional iron deficiency in CKD, including blood losses, impaired iron absorption, and chronic inflammation. The traditional biomarkers used for the diagnosis of iron-deficiency anemia (IDA) in patients with CKD have limitations, leading to persistent challenges in the detection and monitoring of IDA in these patients. Here, we review the pathophysiology and available diagnostic tests for IDA in CKD, we discuss the literature that has informed the current practice guidelines for the treatment of IDA in CKD, and we summarize the available oral and intravenous (IV) iron formulations for the treatment of IDA in CKD. Two important issues are addressed, including the potential risks of a more liberal approach to iron supplementation as well as the potential risks and benefits of IV versus oral iron supplementation in patients with CKD., (Copyright © 2020 by the American Society of Nephrology.)

The FDA has recently endorsed metformin use in patients with T2D and stage 3 CKD (CKD3). However, metformin safety in elderly individuals is unknown. The aim of this study was to identify frequency and risk factors of lactic acid (LA) elevation in ambulatory elderly male US veterans with stable diabetic CKD3 treated with metformin. We studied 92 patients with non-diabetic CKD3 (Group1), diabetic CKD3 not on metformin (Group2) and diabetic CKD3 on metformin (Group 3). Mean LA levels were similar at 1.3 ± 0.3 and 1.3 ± 0.4 mmol/L in Groups 1 and 2, respectively; while, LA was significantly higher in Group 3 (2.1 ± 1.0 mmol/L, P < .001). Only 1 patient in each Groups 1 (4%) and 2 (4%) had hyperlactatemia (LA > 2.0 mmol/L), as compared with 17 (42.5%) patients in Group 3 (P < .05). No differences in age, BMI, eGFR, metformin dosage, and HbA1c were seen in Group 3 patients with and without hyperlactatemia. In the multivariate logistic regression analyses, metformin use was the only factor significantly associated with hyperlactatemia (adjusted OR 25.48, P < .005). In conclusion, metformin therapy is associated with increased risk of hyperlactatemia in elderly men with diabetic CKD3., (Published by Elsevier Inc.)

Background: Population-based studies show there is a high prevalence of chronic kidney disease (CKD) patients suffering from chronic pain. While opiates are frequently prescribed in non-dialysis-dependent CKD (NDD-CKD) patients, there may be toxic accumulation of metabolites, particularly among those progressing to end-stage renal disease (ESRD). We examined the association of opiate versus other analgesic use during the pre-ESRD period with post-ESRD mortality among NDD-CKD patients transitioning to dialysis., Methods: We examined a national cohort of US Veterans with NDD-CKD who transitioned to dialysis over 2007-14. Among patients who received ≥1 prescription(s) in the Veterans Affairs (VA) Healthcare System within 1 year of transitioning to dialysis, we examined associations of pre-ESRD analgesic status, defined as opiate, gabapentin/pregabalin, other non-opiate analgesic, versus no analgesic use, with post-ESRD mortality using multivariable Cox models., Results: Among 57,764 patients who met eligibility criteria, pre-ESRD opiate and gabapentin/pregabalin use were each associated with higher post-ESRD mortality (ref: no analgesic use), whereas non-opiate analgesic use was not associated with higher mortality in expanded case-mix analyses: HRs (95% CIs) 1.07 (1.05-1.10), 1.07 (1.01-1.13), and 1.00 (0.94-1.06), respectively. In secondary analyses, increasing frequency of opiate prescriptions exceeding 1 opiate prescription in the 1-year pre-ESRD period was associated with incrementally higher post-ESRD mortality (ref: no analgesic use)., Conclusions: In NDD-CKD patients transitioning to dialysis, pre-ESRD opiate and gabapentin/pregabalin use were associated with higher post-ESRD mortality, whereas non-opiate analgesic use was not associated with death. There was a graded association between increasing frequency of pre-ESRD opiate use and incrementally higher mortality., (© 2020 S. Karger AG, Basel.)

Background: Advanced chronic kidney disease (CKD) patients, including those receiving dialysis, have a high prevalence of thyroid dysfunction. Although hypothyroidism is associated with higher death risk in end-stage renal disease (ESRD) patients, no studies have examined whether thyroid status in the pre-ESRD period impacts mortality after dialysis initiation., Methods: Among US veterans with CKD identified from the national Veterans Affairs database that transitioned to dialysis over the period from October 2007 to September 2011, we examined the association of pre-ESRD serum thyrotropin (TSH) levels averaged over the 1-year pre-dialysis ('prelude') period with all-cause mortality in the first year following dialysis initiation., Results: Among 15 335 patients in the 1-year prelude cohort, TSH levels >5.0 mIU/L were associated with higher mortality in expanded case-mix Cox models (reference: TSH 0.5-5.0 mIU/L): adjusted hazard ratio (aHR) [95% confidence interval (CI) 1.20 (1.07-1.33). Similar findings were observed for TSH >5.0 mIU/L and mortality in the 2- and 5-year cohorts: aHRs (95% CI) 1.11 (1.02-1.21) and 1.15 (1.07-1.24), respectively. Analyses of finer gradations of TSH in the 1-year prelude cohort demonstrated that incrementally higher levels >5.0 mIU/L were associated with increasingly higher mortality in expanded case-mix models (reference: TSH 0.5-3.0 mIU/L): aHRs (95% CI) 1.18 (1.04-1.33) and 1.28 (1.03-1.59) for TSH levels >5.0-10.0 mIU/L and >10.0 mIU/L, respectively. In the 2- and 5-year cohorts, mortality associations persisted most strongly for those with TSH >10.0 mIU/L, particularly after laboratory covariate adjustment., Conclusions: Among new ESRD patients, there is a dose-dependent relationship between higher pre-ESRD TSH levels >5.0 mIU/L and post-ESRD mortality. Further studies are needed to determine the impact of TSH reduction with thyroid hormone supplementation in this population., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Previous studies reported that compared with percutaneous coronary interventions (PCIs), coronary artery bypass grafting (CABG) is associated with a reduced risk of mortality and repeat revascularization in patients with mild to moderate chronic kidney disease (CKD) and end-stage renal disease (ESRD). Information about outcomes associated with CABG versus PCI in patients with advanced stages of CKD is limited. We evaluated the incidence and relative risk of acute kidney injury (AKI) associated with CABG versus PCI in patients with advanced CKD., Methods: We examined 730 US veterans with incident ESRD who underwent a first CABG or PCI up to 5 years prior to dialysis initiation. The association of CABG versus PCI with AKI was examined in multivariable adjusted logistic regression analyses., Results: A total of 466 patients underwent CABG and 264 patients underwent PCI. The mean age was 64 ± 8 years, 99% were male, 20% were African American and 84% were diabetic. The incidence of AKI in the CABG versus PCI group was 67% versus 31%, respectively (P < 0.001). The incidence of all stages of AKI were higher after CABG compared with PCI. CABG was associated with a 4.5-fold higher crude risk of AKI {odds ratio [OR] 4.53 [95% confidence interval (CI) 3.28-6.27]; P < 0.001}, which remained significant after multivariable adjustments [OR 3.50 (95% CI 2.03-6.02); P < 0.001]., Conclusion: CABG was associated with a 4.5-fold higher risk of AKI compared with PCI in patients with advanced CKD. Despite other benefits of CABG over PCI, the extremely high risk of AKI associated with CABG should be considered in this vulnerable population when deciding on the optimal revascularization strategy., (Published by Oxford University Press on behalf of ERA-EDTA 2018. This work is written by US Government employees and is in the public domain in the US.)

Background: In the general population, elevated triglyceride (TG) levels are an important risk factor for cardiovascular disease and mortality. However, in chronic kidney disease, the association of serum TGs with mortality is less clear., Objective: We sought to examine the association of TGs with mortality across chronic kidney disease (CKD) stages in a large cohort of U.S. veterans., Methods: We examined 2,086,904 U.S. veterans with a TG measurement obtained between a baseline period of October 2004 and September 2006, with follow-up until December 2014 (median [interquartile range {IQR}]: 9.2 [6.5, 9.9] years). Associations of TGs with all-cause and cardiovascular mortality across CKD stages were evaluated using Cox proportional hazard models., Results: Patients were 64 ± 14 years old with a median (IQR) baseline TG of 129 [88, 193] mg/dL and estimated glomerular filtration rate of 76 [61, 91] mL/min/1.73 m 2 . More advanced CKD was associated with higher odds of TGs ≥ 240 mg/dL. Low levels of TGs < 80 mg/dL were associated with a higher risk of mortality across all stages, whereas TG levels ≥ 240 mg/dL were only associated with a higher risk of all-cause mortality in non-CKD and CKD stages 3A, 3B, and 4 (reference: TG 120 to <160 mg/dL). The relationship of higher TGs with mortality incrementally attenuated across worsening stages of CKD and attenuated to the null among patients with CKD stage 5/end-stage renal disease. Similar results were observed for cardiovascular mortality, in strata by age and diabetes, and further adjustment for high-density lipoprotein and low-density lipoprotein., Conclusion: Associations of elevated TGs with all-cause and cardiovascular mortality were incrementally attenuated across more advanced stages of CKD., (Published by Elsevier Inc.)

Chronic kidney disease (CKD), defined by low estimated glomerular filtration rate (eGFR), contributes to global morbidity and mortality. Here we conduct a transethnic Genome-Wide Association Study of eGFR in 280,722 participants of the Million Veteran Program (MVP), with replication in 765,289 participants from the Chronic Kidney Disease Genetics (CKDGen) Consortium. We identify 82 previously unreported variants, confirm 54 loci, and report interesting findings including association of the sickle cell allele of betaglobin among non-Hispanic blacks. Our transcriptome-wide association study of kidney function in healthy kidney tissue identifies 36 previously unreported and nine known genes, and maps gene expression to renal cell types. In a Phenome-Wide Association Study in 192,868 MVP participants using a weighted genetic score we detect associations with CKD stages and complications and kidney stones. This investigation reinterprets the genetic architecture of kidney function to identify the gene, tissue, and anatomical context of renal homeostasis and the clinical consequences of dysregulation.

Objective: Serum albumin is a marker of malnutrition and inflammation and has been demonstrated as a strong predictor of mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. Yet, whether serum albumin levels in late-stage CKD are associated with adverse outcomes after the transition to ESRD is unknown. We hypothesize that lower levels and a decline in serum albumin in late-stage CKD are associated with higher risk of mortality and hospitalization rates 1 year after transition to ESRD., Design and Methods: This retrospective cohort study included 29,124 US veterans with advanced CKD transitioning to ESRD between 2007 and 2015. We evaluated the association of pre-ESRD (91 days before transition) serum albumin with 12-month post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates as well as the association of 1-year pre-ESRD albumin slope and 12-month post-ESRD mortality using hierarchical multivariable adjustments., Results: There was a negative linear association between serum albumin and all-cause mortality, such that risk doubled (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.87, 2.28) for patients with the lowest serum albumin <2.8 g/dL (ref: ≥4.0 g/dL) after full adjustment. A consistent relationship was observed between serum albumin and cardiovascular and infection-related mortality, and hospitalization outcomes. An increase in serum albumin of >0.25 g/dL/year was associated with reduced mortality risk (HR: 0.76, 95% CI: 0.63, 0.91) compared with a slight decline in albumin (ref: >-0.25 to 0 g/dL/year), whereas a decline more than 0.5 g/dL/year was associated with a 55% higher risk in mortality (HR: 1.55, 95% CI: 1.43, 1.68) in fully adjusted models., Conclusions: Lower pre-ESRD serum albumin was associated with higher post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates. Declining serum albumin levels in the pre-ESRD period were also associated with worse 12-month post-ESRD mortality., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Pneumococcal vaccine is recommended for adults 65 years and older and those younger than 65 years with clinical indications (eg, diabetes, lung/heart disease, kidney failure, and nephrotic syndrome). Its cost-effectiveness in less severe chronic kidney disease (CKD) is uncharacterized., Study Design: Cost-effectiveness analysis., Setting & Population: US adults aged 50 to 64 and 65 to 79 years stratified by CKD risk status: no CKD (estimated glomerular filtration rate≥60mL/min/1.73m 2 and urinary albumin-creatinine ratio<30mg/g), CKD with moderate risk, CKD with high risk, and kidney failure (estimated glomerular filtration rate<15mL/min/1.73m 2 ) or nephrotic-range albuminuria (urinary albumin-creatinine ratio≥2,000mg/g). Data sources were the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004, Centers for Disease Control and Prevention, and the Atherosclerosis Risk in Communities (ARIC) Study., Intervention(s): Vaccination compared to no vaccination., Outcomes: Incremental cost-effectiveness ratios based on US dollars per quality-adjusted life-year (QALY)., Model, Perspective, & Timeframe: Markov model, US health sector perspective, and lifetime horizon., Results: The prevalence of pneumococcal vaccination in NHANES 1999 to 2004 was 56.6% (aged 65-79 years), 28.5% (aged 50-64 years with an indication), and 9.7% (aged 50-64 years without an indication), with similar prevalences across CKD risk status. Pneumococcal vaccination was overall cost-effective (

Objectives: Among kidney disease patients ≥80 years progressing to end-stage renal disease, there is growing interest in conservative nondialytic management approaches. However, among those who have initiated hemodialysis, little is known about the impact of withdrawal from dialysis on mortality, nor the patient characteristics associated with withdrawal from dialysis., Study Design: Historical cohort study., Setting and Participants: We examined 133,162 incident hemodialysis patients receiving care within a large national dialysis organization from 2007 to 2011., Measures: We identified patients who withdrew from dialysis, either as a listed cause of death or censor reason. Incidence rates and subdistribution hazard ratios for withdrawal from dialysis as well as 4 other censoring reasons were examined across age groups. In addition, demographic and clinical characteristics associated with withdrawal from dialysis therapy among patients ≥80 years old was assessed using logistic regression analysis., Results: Among 17,296 patients aged ≥80 years, 10% of patients withdrew from dialysis. Duration from the last hemodialysis treatment to death was 10 [interquartile range 6-16] days in patients with available data. Withdrawal from dialysis was the second and third most common cause of death among patients aged ≥80 years and <80 years, respectively. Among patients ≥80 years, minorities were much less likely than non-Hispanic whites to stop dialysis. Other factors associated with higher odds of dialysis withdrawal included having a central venous catheter compared to an arteriovenous fistula at dialysis start, dementia, living in mid-west regions, and less favorable markers associated with malnutrition-inflammation-cachexia syndrome such as higher white blood cell counts and lower body mass index, albumin, and normalized protein catabolic rate., Conclusion/implications: Among very-elderly incident hemodialysis patients, dialysis therapy withdrawal exhibits wide variations across age, race and ethnicity, regions, cognitive status, dialysis vascular access, and nutritional status. Further studies examining implications of withdrawal from dialysis in older patients are warranted., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Data from clinical trials to inform practice in maintenance hemodialysis are limited. Incorporating randomized trials into dialysis clinical care delivery should help generate practice-guiding evidence, but the feasibility of this approach has not been established., Methods: To develop approaches for embedding trials into routine delivery of maintenance hemodialysis, we performed a cluster-randomized, pragmatic trial demonstration project, the Time to Reduce Mortality in ESRD (TiME) trial, evaluating effects of session duration on mortality (primary outcome) and hospitalization rate. Dialysis facilities randomized to the intervention adopted a default session duration ≥4.25 hours (255 minutes) for incident patients; those randomized to usual care had no trial-driven approach to session duration. Implementation was highly centralized, with no on-site research personnel and complete reliance on clinically acquired data. We used multiple strategies to engage facility personnel and participating patients., Results: The trial enrolled 7035 incident patients from 266 dialysis units. We discontinued the trial at a median follow-up of 1.1 years because of an inadequate between-group difference in session duration. For the primary analysis population (participants with estimated body water ≤42.5 L), mean session duration was 216 minutes for the intervention group and 207 minutes for the usual care group. We found no reduction in mortality or hospitalization rate for the intervention versus usual care., Conclusions: Although a highly pragmatic design allowed efficient enrollment, data acquisition, and monitoring, intervention uptake was insufficient to determine whether longer hemodialysis sessions improve outcomes. More effective strategies for engaging clinical personnel and patients are likely required to evaluate clinical trial interventions that are fully embedded in care delivery., (Copyright © 2019 by the American Society of Nephrology.)

Background Although studies have shown that statin therapy in patients with non-dialysis-dependent chronic kidney disease was associated with a lower risk of death, this was not observed in dialysis patients newly initiated on statins. It is unclear if statin therapy benefits administered during the predialysis period persist after transitioning to end-stage renal disease. Methods and Results In 47 720 veterans who transitioned to end-stage renal disease during 2007 to 2014, we examined the association of statin therapy use 1 year before transition with posttransition all-cause and cardiovascular mortality and hospitalization incidence rates over the first 12 months of follow-up. Associations were examined using multivariable adjusted Cox proportional hazard models and negative binomial regressions. Sensitivity analyses included propensity score and subgroup analyses. The cohort's mean± SD age was 71±11 years, and the cohort included 4% women, 23% blacks, and 66% diabetics. Over 12 months of follow-up, there were 13 411 deaths, with an incidence rate of 35.3 (95% CI , 34.7-35.8) deaths per 100 person-years. In adjusted models, statin therapy compared with no statin therapy was associated with lower risks of 12-month all-cause (hazard ratio [95% CI], 0.79 [0.76-0.82]) and cardiovascular (hazard ratio [95% CI ], 0.83 [0.78-0.88]) mortality, as well as with a lower rate of hospitalizations (incidence rate ratio [95% CI ], 0.89 [0.87-0.92]) after initiating dialysis. These lower outcome risks persisted across strata of clinical characteristics, and in propensity score analyses. Conclusions Among veterans with non-dialysis-dependent chronic kidney disease, treatment with statin therapy within the 1 year before transitioning to end-stage renal disease is associated with favorable early end-stage renal disease outcomes.

Objective: The impact of glycemic control in diabetic patients with chronic kidney disease (CKD) who may or may not transition to dialysis remains uncertain, given recent interest in the conservative management of advanced CKD without dialysis therapy, which may benefit from alternative glycemic control strategies., Design and Methods: Among a national cohort of US Veterans, we examined the association of glycemic status, defined by averaged random blood glucose and hemoglobin A1c (HbA1c), with mortality after transitioning to dialysis over 2007-2011 (Transition Cohort) compared with patients in a one-to-one matched cohort of CKD patients with diabetes who did not transition to dialysis (Nontransition Cohort)., Results: Among 17,121 patients in the Transition Cohort, averaged random glucose ≥200 mg/dL was associated with higher mortality in expanded case-mix analyses (reference: 100-<120 mg/dL): adjusted hazard ratio (95% confidence interval) 1.26 (1.13-1.40). In the transition cohort, HbA1c 8-<10% and ≥10% were associated with higher mortality (reference: 6-<8%): adjusted hazard ratios (95% confidence interval) 1.21 (1.11-1.33) and 1.43 (1.21-1.69), respectively. Among 8,711 patients in the Nontransition Cohort, averaged random glucose <100 mg/dl and ≥160 mg/dl were associated with higher death risk, whereas HbA1c was not associated with mortality., Conclusion: In diabetic CKD patients transitioning to dialysis, higher averaged random glucose and HbA1c were associated with early dialysis mortality, whereas in matched CKD patients who did not transition, both lower and higher glucose levels were associated with higher mortality. These data suggest the need for different glycemic strategies based on whether there are plans to transition to dialysis versus pursue conservative management among diabetic patients with CKD., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Coronary artery bypass grafting (CABG) is associated with better survival than percutaneous coronary intervention (PCI) in patients with mild-to-moderate chronic kidney disease (CKD) and End-Stage Renal Disease (ESRD). However, the optimal strategy for coronary artery revascularization in advanced CKD patients who transition to ESRD is unclear., Methods: We examined a contemporary national cohort of 971 US veterans with incident ESRD, who underwent first CABG or PCI up to 5 years prior to dialysis initiation. We examined the association of a history of CABG versus PCI with all-cause mortality following transition to dialysis, using Cox proportional hazards models adjusted for time between procedure and dialysis initiation, socio-demographics, comorbidities and medications., Results: 582 patients underwent CABG and 389 patients underwent PCI. The mean age was 66±8 years, 99% of patients were male, 79% were white, 19% were African Americans, and 84% were diabetics. The all-cause post-dialysis mortality rates after CABG and PCI were 229/1000 patient-years (PY) [95% CI: 205-256] and 311/1000PY [95% CI: 272-356], respectively. Compared to PCI, patients who underwent CABG had 34% lower risk of death [multivariable adjusted Hazard Ratio (95% CI) 0.66 (0.51-0.86), p=0.002] after initiation of dialysis. Results were similar in all subgroups of patients stratified by age, race, type of intervention, presence/absence of myocardial infarction, congestive heart failure and diabetes., Conclusion: CABG in advanced CKD patients was associated lower risk of death after initiation of dialysis compared to PCI., Competing Interests: Disclosures: None of the authors have relevant conflicts of interest.

Background and Aims: Constipation is one of the most frequent symptoms encountered in daily clinical practice and is implicated in the development of atherosclerosis, potentially through altered gut microbiota. However, little is known about its association with incident cardiovascular events., Methods: In a nationally representative cohort of 3,359,653 US veterans with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m 2 between October 1, 2004 and September 30, 2006 (baseline period), with follow-up through 2013, we examined the association of constipation status (absence or presence; defined using diagnostic codes and laxative use) and laxative use (none, one, or ≥2 types of laxatives) with all-cause mortality, incident coronary heart disease (CHD), and incident ischemic stroke., Results: Among 3,359,653 patients, 237,855 (7.1%) were identified as having constipation. After multivariable adjustments for demographics, prevalent comorbidities, medications, and socioeconomic status, patients with (versus without) constipation had 12% higher all-cause mortality (hazard ratio [HR], 1.12; 95% CI, 1.11-1.13), 11% higher incidence of CHD (HR, 1.11; 95% CI, 1.08-1.14), and 19% higher incidence of ischemic stroke (HR, 1.19; 95% CI, 1.15-1.22). Patients with one and ≥2 (versus none) types of laxatives experienced a similarly higher risk of all-cause mortality (HRs [95% CI], 1.15 [1.13-1.16] and 1.14 [1.12-1.15], respectively), incident CHD (HRs [95% CI], 1.11 [1.07-1.15] and 1.10 [1.05-1.15], respectively) and incident ischemic stroke (HRs [95% CI], 1.19 [1.14-1.23] and 1.21 [1.16-1.26], respectively)., Conclusions: Constipation status and laxative use are independently associated with higher risk of all-cause mortality and incident CHD and ischemic stroke., (Published by Elsevier B.V.)

Background: Abnormalities in serum potassium are risk factors for sudden cardiac death and arrhythmias among dialysis patients. Although a previous study in hemodialysis patients has shown that race/ethnicity may impact the relationship between serum potassium and mortality, the relationship remains unclear among peritoneal dialysis (PD) patients where the dynamics of serum potassium is more stable., Methods: Among 17,664 patients who started PD between January 1, 2007 and December 31, 2011 in a large US dialysis organization, we evaluated the association of serum potassium levels with all-cause and arrhythmia-related deaths across race/ethnicity using time-dependent Cox models with adjustments for demographics. We also used restricted cubic spline functions for serum potassium levels to explore non-linear associations., Results: Baseline serum potassium levels were the highest among Hispanics (4.2 ± 0.7 mEq/L) and lowest among non-Hispanic blacks (4.0 ± 0.7 mEq/L). Among 2,949 deaths during the follow-up of median 2.2 (interquartile ranges 1.3-3.2) years, 683 (23%) were arrhythmia-related deaths. Overall, both hyperkalemia and hypokalemia (i.e., serum potassium levels >5.0 and <3.5 mEq/L, respectively) were associated with higher all-cause and arrhythmia-related mortality. In a stratified analysis according to race/ethnicity, the association of hypokalemia with all-cause and arrhythmia-related mortality was consistent with an attenuation for arrhythmia-related mortality in non-Hispanic blacks. Hyperkalemia was associated with all-cause and arrhythmia-related mortality in non-Hispanic whites and non-Hispanic blacks, but no association was observed in Hispanics., Conclusion: Among incident PD patients, hypokalemia was consistently associated with all-cause and arrhythmia-related deaths irrespective of race/ethnicity. However, while hyperkalemia was associated with both death outcomes in non-Hispanic blacks and whites, it was not associated with either death outcome in Hispanic patients. Further studies are needed to demonstrate whether different strategies should be followed for the management of serum potassium levels according to race/ethnicity., (© 2019 S. Karger AG, Basel.)

Background: To determine the association of vancomycin with acute kidney injury (AKI) in relation to its serum concentration value and to examine the risk of AKI in patients treated with vancomycin when compared with a matched cohort of patients receiving non-glycopeptide antibiotics (linezolid/daptomycin)., Methods: From a cohort of > 3 million US veterans with baseline estimated glomerular filtration rate ≥60 mL/min/1.73 m2, we identified 33,527 patients who received either intravenous vancomycin (n = 22,057) or non-glycopeptide antibiotics (linezolid/daptomycin, n = 11,470). We examined the association of the serum trough vancomycin level recorded within the first 48 h of administration with subsequent AKI in all patients treated with vancomycin and association of vancomycin vs. non-glycopeptide antibiotics use with the risk of incident AKI., Results: The overall multivariable adjusted ORs of AKI stages 1, 2, and 3 in patients on vancomycin vs. non-glycopeptides were 1.1 (1.1-1.2), 1.2 (1-1.4), and 1.4 (1.1-1.7), respectively. When examined in strata divided by vancomycin trough level, the odds of AKI were similar or lower in patients receiving vancomycin compared to non-glycopeptide antibiotics as long as serum vancomycin levels were ≤20 mg/L. However, in patients with serum vancomycin levels > 20 mg/L, the ORs of AKI stages 1, 2, and 3 in patients on vancomycin vs. non-glycopeptide antibiotics were 1.5 (1.4-1.7), 1.9 (1.5-2.3), and 2.7 (2-3.5), respectively., Conclusions: Vancomycin use is associated with a higher risk of AKI when serum levels exceed > 20 mg/L., (© 2019 S. Karger AG, Basel.)

Background: Diabetes remains a growing public health threat but evidence supports the role that pharmacists can play in improving diabetes medication use and outcomes. To improve the quality of care, the Veterans Health Administration has widely adopted care models that integrate clinical pharmacists, but more data are needed to interpret the impact of these services. Our objective was to assess clinical pharmacy services' impact on outcomes and oral antidiabetic medication (OAD) use among veterans with uncontrolled diabetes in the first year of therapy., Methods: This was a retrospective cohort analysis using the Veterans Affairs (VA) Corporate Data Warehouse to identify the first diagnosis of and initiation of OAD therapy for uncomplicated, uncontrolled diabetes (A1C > 7.0%) during 2002-2014. Receipt of clinical pharmacy services was identified using codes within VA electronic health records, and clinical values were obtained at or near the initial fill date and 365 days later. Use of OADs was assessed by proportion of days covered (PDC) for one year following the first filled prescription. Veterans having received clinical pharmacy services were matched 1:1 to those having not seen a clinical pharmacist in the first year of therapy, and generalized linear models assessed changes and differences in outcomes., Results: The analysis included 5749 patients in each cohort. On average, patients saw a clinical pharmacist 2.5 times throughout the first year of OAD therapy. Adherence to OAD medications was higher in veterans having seen a pharmacist (84.3% vs. 82.4%, p < 0.0001) and more such patients achieved a PDC of at least 80% (72.2% vs. 68.2%, p < 0.0001). After one year of OAD therapy, mean change in hemoglobin A1C was greater among those receiving pharmacy services (- 1.5% vs. -1.4%, p < 0.0001)., Conclusion: Pharmacist participation in diabetes patients' primary care positively affects the multifaceted needs of patients with this condition and comorbid chronic disease.

Objective: To examine whether chronic insomnia is associated with an increased risk of adverse renal outcomes and all-cause mortality., Patients and Methods: We examined associations of chronic insomnia (defined as the presence of both International Classification of Diseases, Ninth Revision codes 307.42, 307.49, and 780.52 and long-term use of insomnia medications) with adverse renal outcomes (end-stage renal disease, incidence of estimated glomerular filtration rate [eGFR] ≤45 mL/min per 1.73 m 2 , and eGFR slopes <-3.0 mL/min per 1.73 m 2 per year) and all-cause mortality in a national cohort of 1,639,090 US veterans by using Cox proportional hazards and logistic regression models with multivariable adjustments., Results: A total of 36,741 patients (2.24%) had chronic insomnia; 32,985 (89.8%) were male and 28,090 (76.5%) were white, with a mean baseline eGFR of 84.1±16.4 mL/min per 1.73 m 2 . Chronic insomnia was associated with a significantly higher risk of eGFR 45 mL/min per 1.73 m 2 or less (multivariable-adjusted hazard ratio [HR], 1.39; 95% CI, 1.34-1.44; P<.001), and rapid loss of kidney function (odds ratio, 1.07; 95% CI, 1.03-1.12; P=.002), but not end-stage renal disease (HR, 1.25; 95% CI, 0.81-1.93; P=.32). Chronic insomnia was not associated with a higher risk of all-cause mortality (HR, 1.00; 95% CI, 0.97-1.03; P=.99)., Conclusion: Chronic insomnia is associated with a higher risk of development and progression of chronic kidney disease, but not ESRD. Further studies are needed to establish the underlying mechanisms of action and to determine whether treatment of insomnia could be beneficial to prevent deteriorating kidney function., (Published by Elsevier Inc.)

Objective: To develop and validate a risk prediction model that would help individualize treatment and improve the shared decision-making process between clinicians and patients., Patients and Methods: We developed a risk prediction tool for mortality during the first year of dialysis based on pre-end-stage renal disease characteristics in a cohort of 35,878 US veterans with incident end-stage renal disease who transitioned to dialysis treatment between October 1, 2007, and March 31, 2014 and then externally validated this tool among 4284 patients in the Kaiser Permanente Southern California (KPSC) health care system who transitioned to dialysis treatment between January 1, 2007, and September 30, 2015., Results: To ensure model goodness of fit, 2 separate models were selected for patients whose last estimated glomerular filtration rate (eGFR) before dialysis initiation was less than 15 mL/min per 1.73 m 2 or 15 mL/min per 1.73 m 2 or higher. Model discrimination in the internal validation cohort of veterans resulted in C statistics of 0.71 (95% CI, 0.70-0.72) and 0.66 (95% CI, 0.65-0.67) among patients with eGFR lower than 15 mL/min per 1.73 m 2 and 15 mL/min per 1.73 m 2 or higher, respectively. In the KPSC external validation cohort, the developed risk score exhibited C statistics of 0.77 (95% CI, 0.74-0.79) in men and 0.74 (95% CI, 0.71-0.76) in women with eGFR lower than 15 mL/min per 1.73 m 2 and 0.71 (95% CI, 0.67-0.74) in men and 0.67 (95% CI, 0.62-0.72) in women with eGFR of 15 mL/min per 1.73 m 2 or higher., Conclusion: A new risk prediction tool for mortality during the first year after transition to dialysis (available at www.DialysisScore.com) was developed in the large national Veterans Affairs cohort and validated with good performance in the racially, ethnically, and gender diverse KPSC cohort. This risk prediction tool will help identify high-risk populations and guide management strategies at the transition to dialysis., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether kidney function level and its rate of decline in the immediate predialysis period among veterans transitioning to end-stage renal disease (ESRD) predict postdialysis mortality and hospitalization., Patients and Methods: In 19,985 veterans transitioning to ESRD during the period October 1, 2007, to March 30, 2014, we examined kidney function and its slope over the final year of the pre-ESRD(prelude) period. Two categories of low vs high estimated glomerular filtration rate (eGFR, dichotomized at 10 mL/min/1.73 m 2 ) and slow vs fast slope (dichotomized at -10 mL/min/1.73 m 2 /y) were combined into 4 groups. Their associations with 12-month post-ESRD all-cause and cardiovascular (CV) mortality and hospitalization rates were examined in adjusted models accounting for clinical characteristics and laboratory measurements at transition., Results: Patients, 66±11 years old, and 34% blacks, had a median (interquartile range) eGFR at transition and slope of 9.7 (7.1-13.3) mL/min/1.73 m 2 and -10.5 (-18.8 to -5.9) mL/min/1.73 m 2 /y, respectively. Patients with a low eGFR and slow slope had the lowest 12-month all-cause and CV mortality risks and hospitalization rate. Conversely, patients with high eGFR and fast slope had the highest risk of all-cause and CV mortality and hospitalization rate compared with patients with a low eGFR and slow slope. This relationship persisted in sensitivity analyses, including propensity scoring., Conclusion: A kidney profile of a low eGFR and slow slope in the prelude period is associated with favorable early dialysis outcomes in veteran patients. Trials to examine a more conservative approach to dialysis are warranted., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: The Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS2°P), a 0-to-9-point system based on the presence/absence of 9 clinical factors, was developed to classify the risk of major adverse cardiovascular events (MACE) (a composite of cardiovascular death, recurrent myocardial infarction, or ischemic stroke) among patients with a recent myocardial infarction. Its performance has not been examined internationally outside of a clinical trial setting., Methods and Results: We evaluated the performance of TRS2°P for predicting MACE in 53 599 patients with recent myocardial infarction in 5 international cohorts from New Zealand, South Korea, Sweden, and the United States participating in the Chronic Kidney Disease Prognosis Consortium. Overall, there were 19 444 cases of MACE across 5 cohorts over a mean follow-up of 5 years, and the overall MACE rate ranged from 5.0 to 18.4 (per 100 person-years). The TRS2°P showed modest calibration (Brier score ranged from 0.144 to 0.173) and discrimination (C-statistics >0.61 in all studies except 1 from Korea with 0.55) across cohorts relative to its original Brier score of 0.098 and C-statistic of 0.67 in the derived data set. Although there was some heterogeneity across cohorts, the 9 predictors in the TRS2°P were generally associated with higher MACE risk, with strongest associations observed (meta-analyzed adjusted hazard ratio 1.6-1.7) for history of heart failure, age ≥75 years, and prior stroke, followed by peripheral artery disease, kidney dysfunction, diabetes mellitus, and hypertension (hazard ratio 1.3-1.4). Prior coronary bypass graft surgery and smoking did not reach statistical significance (hazard ratio ≈1.1)., Conclusions: TRS2°P, a simple scoring system with 9 routine clinical factors, was modestly predictive of secondary events when applied in patients with recent myocardial infarction from diverse clinical and geographic settings., (© 2018 The Authors and Merck Sharpe & Dohme Corp. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Objectives: Veterans with ESKD initiate dialysis under the Veterans Health Administration (VHA), an integrated health system, or are outsourced to non-VHA providers. It is unknown whether outcomes differ according to their dialysis provider at initiation. We sought to evaluate the association between dialysis provider and mortality and hospitalization among United States veterans initiating dialysis., Design, Setting, Participants, & Measurements: Among 68,727 United States veterans who initiated dialysis in 2007-2014, we examined the association of dialysis provider (VHA versus non-VHA) at initiation with mortality and hospitalization rates in the first 12 months post-initiation. Associations were examined across adjusted models, accounting for demographics and comorbidities., Results: Patients were 72±11 years, 5% were women, 24% were black, and 10% ( n =7584) initiated at VHA dialysis centers. VHA dialysis center patients were younger, more likely to be black, had fewer cardiovascular comorbidities, and lower eGFR at dialysis initiation. VHA provider patients were more likely to be hospitalized in the first 12 months (adjusted incidence rate ratio, 1.10; 95% confidence interval, 1.07 to 1.14), but had lower all-cause mortality risk (adjusted hazard ratio, 0.87; 95% confidence interval, 0.83 to 0.93) in fully adjusted models., Conclusions: Veteran patients initiating dialysis with a VHA dialysis provider appear to have a lower mortality risk but higher hospitalization rates than veterans initiating dialysis at non-VHA dialysis units., (Copyright © 2018 by the American Society of Nephrology.)

Rheumatoid arthritis is associated with reduced kidney function, possibly due to chronic inflammation or the use of nephrotoxic therapies. However, little is known about the effects of using the newer novel non-nephrotoxic biologic agents on the risk of incident chronic kidney disease (CKD). To study this we used a cohort of 20,757 United States veterans diagnosed with rheumatoid arthritis with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m 2 or more, recruited between October 2004 and September 2006, and followed through 2013. The associations of biologic use with incident CKD (eGFR under 60 with a decrease of at least 25% from baseline, and eGFR under 45 mL/min/1.73m 2 ) and change in eGFR (<-3, -3 to <0 [reference], and ≥0 mL/min/1.73m 2 /year) were examined in propensity-matched patients based on their likelihood to initiate biologic treatment, using Cox models and multinomial logistic regression models, respectively. Among 20,757 patients, 4,617 started biologic therapy. In the propensity-matched cohort, patients treated (versus not treated) with biologic agents had a lower risk of incident CKD (hazard ratios 0.95, 95% confidence interval [0.82-1.10] and 0.71 [0.53-0.94] for decrease in eGFR under 60 and under 45 mL/min/1.73m 2 , respectively) and progressive eGFR decline (multinomial odds ratios [95% CI] for eGFR slopes <-3 and ≥0 [versus -3 to <0] mL/min/1.73m 2 /year, 0.67 [0.58-0.79] and 0.76 [0.69-0.83], respectively). A significant deceleration of eGFR decline was also observed after biologic administration in patients treated with biologics (-1.0 versus -0.4 [mL/min/1.73m 2 /year] before and after biologic use). Thus, biologic agent administration was independently associated with lower risk of incident CKD and progressive eGFR decline., (Published by Elsevier Inc.)

Background: Higher serum alkaline phosphatase (ALP) levels have been associated with excess mortality in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD). However, little is known about the impact of late-stage NDD-CKD ALP levels on outcomes after dialysis initiation., Methods: Among 17 732 US veterans who transitioned to dialysis between October 2007 and September 2011, we examined the association of serum ALP levels averaged over the last 6 months of the pre-ESRD transition period ('prelude period') with all-cause, cardiovascular and infection-related mortality following dialysis initiation, using Cox (for all-cause mortality) and competing risk (for cause-specific mortality) regressions adjusted for demographics, comorbidities, medications, estimated glomerular filtration rate and serum albumin levels over the 6-month prelude period, and vascular access type at dialysis initiation., Results: During a median follow-up of 2.0 (interquartile range, 1.1-3.2) years following dialysis initiation, a total of 9196 all-cause deaths occurred. Higher ALP levels were incrementally associated with higher all-cause, cardiovascular and infection-related mortality. Compared with patients in the lowest ALP quartile (<66.0 U/L), those in the highest quartile (≥111.1 U/L) had multivariable-adjusted hazard/subhazard ratios (95% confidence interval) of 1.42 (1.34-1.51), 1.43 (1.09-1.88) and 1.39 (1.09-1.78) for all-cause, cardiovascular and infection-related mortality, respectively. The associations remained consistent in various subgroups and after further adjustment for liver enzymes, serum phosphorus and intact parathyroid hormone levels., Conclusions: Higher pre-ESRD serum ALP levels are independently associated with higher post-ESRD mortality risk. Further studies are warranted to determine if interventions that lower pre-ESRD ALP levels reduce mortality in incident dialysis patients., (Published by Oxford University Press on behalf of ERA-EDTA 2017. This work is written by US Government employees and is in the public domain in the US.)