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Purpose of Review: Initiation of hemodialysis treatment with a thrice-weekly prescription is currently the standard of care irrespective of patients' residual kidney function (RKF), comorbidities, and preferences., Recent Findings: Each year ∼12 000 Veterans with advanced kidney disease progress to end-stage kidney disease (ESKD) requiring dialysis and comprise greater than 10% of the US incident ESKD population. Dialysis is costly and is associated with impaired health-related quality of life (HRQOL) and high mortality risk, especially in the first year of treatment. Evidence suggests an incremental dialysis transition using twice-weekly hemodialysis provides various benefits, including more dialysis-free time, longer RKF preservation, less vascular access damage, and lower patient burden. Pragmatic studies are needed to inform the efficacy and safety of incremental hemodialysis as a personalized dialysis regimen, and could inform its consideration as a conservation strategy during times of supply shortages. Broadly implementing twice-weekly hemodialysis could also potentially allow more Veterans to receive care within VA-based dialysis units. The VA IncHVets Trial is a pragmatic, multicenter, randomized controlled trial comparing the efficacy and safety of twice-weekly incremental vs. thrice-weekly hemodialysis among Veterans transitioning to ESKD., Summary: Further research is needed to determine whether incremental hemodialysis is well tolerated, effective, and facilitates a more favorable transition to dialysis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: In the general population, continuous glucose monitoring (CGM) provides convenient and less-invasive glucose measurements than conventional self-monitored blood glucose and results in reduced hypoglycemia and hyperglycemia and increased time in target glucose range. However, accuracy of CGM versus blood glucose is not well established in hemodialysis patients., Research Design and Methods: Among 31 maintenance hemodialysis patients with diabetes hospitalized from October 2020 to May 2021, we conducted protocolized glucose measurements using Dexcom G6 CGM versus blood glucose, with the latter measured before each meal and at night, plus every 30-min during hemodialysis. We examined CGM-blood glucose correlations and agreement between CGM versus blood glucose using Bland-Altman plots, percentage of agreement, mean and median absolute relative differences (ARDs), and consensus error grids., Results: Pearson and Spearman correlations for averaged CGM versus blood glucose levels were 0.84 and 0.79, respectively; Bland-Altman showed the mean difference between CGM and blood glucose was ∼+15 mg/dL. Agreement rates using %20/20 criteria were 48.7%, 47.2%, and 50.2% during the overall, hemodialysis, and nonhemodialysis periods, respectively. Mean ARD (MARD) was ∼20% across all time periods; median ARD was 19.4% during the overall period and was slightly lower during nonhemodialysis (18.2%) versus hemodialysis periods (22.0%). Consensus error grids showed nearly all CGM values were in clinically acceptable zones A (no harm) and B (unlikely to cause significant harm)., Conclusions: In hemodialysis patients with diabetes, although MARD values were higher than traditional optimal analytic performance thresholds, error grids showed nearly all CGM values were in clinically acceptable zones. Further studies are needed to determine whether CGM improves outcomes in hemodialysis patients., (© 2024 by the American Diabetes Association.)

Dialysis patients experience frequent hospitalizations and a higher mortality rate compared to other Medicare populations, in whom hospitalizations are a major contributor to morbidity, mortality, and healthcare costs. Patients also typically remain on dialysis for the duration of their lives or until kidney transplantation. Hence, there is growing interest in studying the spatiotemporal trends in the correlated outcomes of hospitalization and mortality among dialysis patients as a function of time starting from transition to dialysis across the United States Utilizing national data from the United States Renal Data System (USRDS), we propose a novel multivariate spatiotemporal functional principal component analysis model to study the joint spatiotemporal patterns of hospitalization and mortality rates among dialysis patients. The proposal is based on a multivariate Karhunen-Loéve expansion that describes leading directions of variation across time and induces spatial correlations among region-specific scores. An efficient estimation procedure is proposed using only univariate principal components decompositions and a Markov Chain Monte Carlo framework for targeting the spatial correlations. The finite sample performance of the proposed method is studied through simulations. Novel applications to the USRDS data highlight hot spots across the United States with higher hospitalization and/or mortality rates and time periods of elevated risk., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. [br]For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Hypoglycemia is a frequent occurrence in chronic kidney disease patients due to alterations in glucose and insulin metabolism. However, there are sparse data examining the predictors and clinical implications of hypoglycemia including mortality risk among incident hemodialysis patients., Design and Methods: Among 58,304 incident hemodialysis patients receiving care from a large national dialysis organization over 2007-2011, we examined clinical characteristics associated with risk of hypoglycemia, defined as a blood glucose concentration <70 mg/dL, in the first year of dialysis using expanded case-mix + laboratory logistic regression models. We then examined the association between hypoglycemia during the first year of dialysis with all-cause mortality using expanded case-mix + laboratory Cox models., Results: In the first year of dialysis, hypoglycemia was observed among 16.8% of diabetic and 6.9% of nondiabetic incident hemodialysis patients. In adjusted logistic regression models, clinical characteristics associated with hypoglycemia included younger age, female sex, African-American race, presence of a central venous catheter, lower residual renal function, and longer dialysis session length. In the overall cohort, patients who experienced hypoglycemia had a higher risk of all-cause mortality risk (reference: absence of hypoglycemia): adjusted hazard ratio (95% confidence interval) 1.08 (1.04, 1.13). In stratified analyses, hypoglycemia was also associated with higher mortality risk in the diabetic and nondiabetic subgroups: adjusted hazard ratios (95% confidence interval's) 1.08 (1.04-1.13), and 1.17 (0.94-1.45), respectively., Conclusions: Hypoglycemia was a frequent occurrence among both diabetic and nondiabetic hemodialysis patients and was associated with a higher mortality risk. Further studies are needed to identify approaches that reduce hypoglycemia risk in the hemodialysis population., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

While dialysis has been the prevailing treatment paradigm for patients with advanced chronic kidney disease (CKD), emphasis on conservative and preservative management in which dietary interventions are a major cornerstone have emerged. Based on high-quality evidence, international guidelines support the utilization of low-protein diets as an intervention to reduce CKD progression and mortality risk, although the precise thresholds (if any) for dietary protein intake vary across recommendations. There is also increasing evidence demonstrating that plant-dominant low-protein diets reduce the risk of developing incident CKD, CKD progression, and its related complications including cardiometabolic disease, metabolic acidosis, mineral and bone disorders, and uremic toxin generation. In this review, we discuss the premise for conservative and preservative dietary interventions, specific dietary approaches used in conservative and preservative care, potential benefits of a plant-dominant low-protein diet, and practical implementation of these nutritional strategies without dialysis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Over 782 000 individuals in the United States have end-stage kidney disease with about 72% of patients on dialysis, a life-sustaining treatment. Dialysis patients experience high mortality and frequent hospitalizations, at about twice per year. These poor outcomes are exacerbated at key time periods, such as the fragile period after transition to dialysis. In order to study the time-varying effects of modifiable patient and dialysis facility risk factors on hospitalization and mortality, we propose a novel Bayesian multilevel time-varying joint model. Efficient estimation and inference is achieved within the Bayesian framework using Markov chain Monte Carlo, where multilevel (patient- and dialysis facility-level) varying coefficient functions are targeted via Bayesian P-splines. Applications to the United States Renal Data System, a national database which contains data on nearly all patients on dialysis in the United States, highlight significant time-varying effects of patient- and facility-level risk factors on hospitalization risk and mortality. Finite sample performance of the proposed methodology is studied through simulations., (© 2022 John Wiley & Sons Ltd.)

(1) Background: Current dietary recommendations for dialysis patients suggest that high phosphorus diets may be associated with adverse outcomes such as hyperphosphatemia and death. However, there has been concern that excess dietary phosphorus restriction may occur at the expense of adequate dietary protein intake in this population. We hypothesized that higher dietary phosphorus intake is associated with higher mortality risk among a diverse cohort of hemodialysis patients. (2) Methods: Among 415 patients from the multi-center prospective Malnutrition, Diet, and Racial Disparities in Kidney Disease Study, we examined the associations of absolute dietary phosphorus intake (mg/day), ascertained by food frequency questionnaires, with all-cause mortality using multivariable Cox models. In the secondary analyses, we also examined the relationship between dietary phosphorus scaled to 1000 kcal of energy intake (mg/kcal) and dietary phosphorus-to-protein ratio (mg/g) with survival. (3) Results: In expanded case-mix + laboratory + nutrition adjusted analyses, the lowest tertile of dietary phosphorus intake was associated with higher mortality risk (ref: highest tertile): adjusted HR (aHR) (95% CI) 3.33 (1.75-6.33). In the analyses of dietary phosphorus scaled to 1000 kcal of energy intake, the lowest tertile of intake was associated with higher mortality risk compared to the highest tertile: aHR (95% CI) 1.74 (1.08, 2.80). Similarly, in analyses examining the association between dietary phosphorus-to-protein ratio, the lowest tertile of intake was associated with higher mortality risk compared to the highest tertile: aHR (95% CI) 1.67 (1.02-2.74). (4) Conclusions: A lower intake of dietary phosphorus was associated with higher mortality risk in a prospective hemodialysis cohort. Further studies are needed to clarify the relationship between specific sources of dietary phosphorus intake and mortality in this population.

Background: Dialysis patients experience a high symptom burden, which may adversely impact their quality of life. Whereas other specialties emphasize routine symptom assessment, symptom burden is not well-characterized in dialysis patients. We sought to examine the prevalence and severity of unpleasant symptoms in a prospective hemodialysis cohort., Methods: Among 122 hemodialysis patients from the prospective Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease (CKD) study, CKD-associated symptoms were ascertained by the Dialysis Symptom Index, a validated survey assessing symptom burden/severity (with higher scores indicating greater symptom severity), over 6/2020-10/2020. We examined the presence of (1) individual symptoms and symptom severity scores, and (2) symptom clusters (defined as ≥ 2 related concurrent symptoms), as well as correlations with clinical characteristics., Results: Symptom severity scores were higher among non-Hispanic White and Hispanic patients, whereas scores were lower in Black and Asian/Pacific Islander patients. In the overall cohort, the most common individual symptoms included feeling tired/lack of energy (71.3%), dry skin (61.5%), trouble falling asleep (44.3%), muscle cramps (42.6%), and itching (42.6%), with similar patterns observed across racial/ethnic groups. The most prevalent symptom clusters included feeling tired/lack of energy + trouble falling asleep (37.7%); trouble falling asleep + trouble staying asleep (34.4%); and feeling tired/lack of energy + trouble staying asleep (32.0%). Lower hemoglobin, iron stores, and dialysis adequacy correlated with higher individual and overall symptom severity scores., Conclusion: We observed a high prevalence of unpleasant symptoms and symptom clusters in a diverse hemodialysis cohort. Further studies are needed to identify targeted therapies that ameliorate symptom burden in CKD., (© 2022. The Author(s).)

Introduction: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are prevalent in patients undergoing maintenance dialysis. Yet, there are limited and mixed evidence on the effects of different dialysis modalities involving longer treatment times or higher frequencies on CKD-MBD markers., Methods: This cohort study used data from 132,523 incident dialysis patients treated with any of the following modalities: conventional thrice-weekly in-center hemodialysis, nocturnal in-center hemodialysis (NICHD), home hemodialysis (HHD), or peritoneal dialysis (PD) from 2007 to 2011. We used marginal structural models fitted with inverse probability weights to adjust for fixed and time-varying confounding and informative censoring. We estimated the average effects of treatments with different dialysis modalities on time-varying serum concentrations of CKD-MBD markers: albumin-corrected calcium, phosphate, parathyroid hormone (PTH), and alkaline phosphatase (ALP) using pooled linear regression., Results: Most of the cohort were exclusively treated with conventional in-center hemodialysis, while few were ever treated with NICHD or HHD. At the baseline, PD patients had the lowest mean and median values of PTH, while NICHD patients had the highest median values. During follow-up, compared to hemodialysis patients, patients treated with NICHD had lower mean serum PTH (19.8 pg/mL [95% confidence interval: 2.8, 36.8] lower), whereas PD and HHD patients had higher mean PTH (39.7 pg/mL [31.6, 47.8] and 51.2 pg/mL [33.0, 69.3] higher, respectively). Compared to hemodialysis patients, phosphate levels were lower for patients treated with NICHD (0.44 mg/dL [0.37, 0.52] lower), PD (0.15 mg/dL [0.12, 0.19] lower), or HHD (0.33 mg/dL [0.27, 0.40] lower). There were no clinically meaningful associations between dialysis modalities and concentrations of calcium or ALP., Conclusion: In incident dialysis patients, compared to treatment with conventional in-center hemodialysis, treatments with other dialysis modalities with longer treatment times or higher frequency were associated with different patterns of serum phosphate and PTH. Given the recent growth in the use of dialysis modalities other than hemodialysis, the associations between the treatment and the CKD-MBD markers warrant additional study., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

End-stage renal disease patients on dialysis experience frequent hospitalizations. In addition to known temporal patterns of hospitalizations over the life span on dialysis, where poor outcomes are typically exacerbated during the first year on dialysis, variations in hospitalizations among dialysis facilities across the US contribute to spatial variation. Utilizing national data from the United States Renal Data System (USRDS), we propose a novel multilevel spatiotemporal functional model to study spatiotemporal patterns of hospitalization rates among dialysis facilities. Hospitalization rates of dialysis facilities are considered as spatially nested functional data (FD) with longitudinal hospitalizations nested in dialysis facilities and dialysis facilities nested in geographic regions. A multilevel Karhunen-Loéve expansion is utilized to model the two-level (facility and region) FD, where spatial correlations are induced among region-specific principal component scores accounting for regional variation. A new efficient algorithm based on functional principal component analysis and Markov Chain Monte Carlo is proposed for estimation and inference. We report a novel application using USRDS data to characterize spatiotemporal patterns of hospitalization rates for over 400 health service areas across the US and over the posttransition time on dialysis. Finite sample performance of the proposed method is studied through simulations., (© 2021 John Wiley & Sons Ltd.)

Background: Lactate dehydrogenase (LDH) plays a role in the glucose metabolism of the human body. Higher LDH levels have been linked to mortality in various cancer types; however, the relationship between LDH and survival in incident hemodialysis (HD) patients has not yet been examined. We hypothesized that higher LDH level is associated with higher death risk in these patients., Methods: We examined the association of baseline and time-varying serum LDH with all-cause, cardiovascular and infection-related mortality among 109 632 adult incident HD patients receiving care from a large dialysis organization in the USA during January 2007 to December 2011. Baseline and time-varying survival models were adjusted for demographic variables and available clinical and laboratory surrogates of malnutrition-inflammation complex syndrome., Results: There was a linear association between baseline serum LDH levels and all-cause, cardiovascular and infection-related mortality in both baseline and time-varying models, except for time-varying infection-related mortality. Adjustment for markers of inflammation and malnutrition attenuated the association in all models. In fully adjusted models, baseline LDH levels ≥360 U/L were associated with the highest risk of all-cause mortality (hazard ratios = 1.19, 95% confidence interval 1.14-1.25). In time-varying models, LDH >280 U/L was associated with higher death risk in all three hierarchical models for all-cause and cardiovascular mortality., Conclusions: Higher LDH level >280 U/L was incrementally associated with higher all-cause and cardiovascular mortality in incident dialysis patients, whereas LDH <240 U/L was associated with better survival. These findings suggest that the assessment of metabolic functions and monitoring for comorbidities may confer survival benefit to dialysis patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Both polypharmacy and frailty are highly prevalent among the patients on hemodialysis and associated with adverse outcomes; however, little is known about the association between them., Methods: We examined 337 patients enrolled in the ACTIVE/ADIPOSE dialysis cohort study between 2009 and 2011. The number of prescribed medications and frailty were assessed at baseline, 12, and 24 months. Frailty was defined based upon the Fried's frailty phenotype. We used logistic regression with generalized estimating equations to model the association of the number of medications and frailty at baseline and over time. A competing-risk regression analysis was also used to assess the association between the number of medications and incidence of frailty., Results: The mean number of medications was 10 ± 5, and 94 patients (28%) were frail at baseline. Patients taking >11 medications showed higher odds for frailty than the patients taking fewer than 8 medications (OR 1.54, 95% CI 1.05-2.26). During the 2-year of follow-up, 87 patients developed frailty among those who were nonfrail at baseline. Compared with the patients taking fewer than 8 medications, the incidence of frailty was approximately 2-fold in those taking >11 medications (sub-distribution hazard ratio 2.15, 95% CI 1.32-3.48)., Conclusions: Using a higher number of medications was associated with frailty and the incidence of frailty among hemodialysis patients. Minimizing polypharmacy may reduce the incidence and prevalence of frailty among dialysis patients., (© 2021 S. Karger AG, Basel.)

Background: Patients with ESRD on maintenance hemodialysis (MHD) are particularly susceptible to dysregulation of energy metabolism, which may manifest as protein energy wasting and cachexia. In recent years, the endocannabinoid system has been shown to play an important role in energy metabolism with potential relevance in ESRD. N-acylethanolamines are a class of fatty acid amides which include the major endocannabinoid ligand, anandamide, and the endogenous peroxisome proliferator-activated receptor-α agonists, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA)., Methods: Serum concentrations of OEA and PEA were measured in MHD patients and their correlations with various clinical/laboratory indices were examined. Secondarily, we evaluated the association of circulating PEA and OEA levels with 12-month all-cause mortality., Results: Both serum OEA and PEA levels positively correlated with high-density lipoprotein-cholesterol levels and negatively correlated with body fat and body anthropometric measures. Serum OEA levels correlated positively with serum interleukin-6 (IL-6) (rho = 0.19; p = 0.004). Serum PEA and IL-6 showed a similar but nonsignificant trend (rho = 0.12; p = 0.07). Restricted cubic spline analyses showed that increasing serum OEA and PEA both trended toward higher mortality risk, and these associations were statistically significant for PEA (PEA ≥4.7 pmol/mL; reference: PEA <4.7 pmol/mL) after adjustments in a Cox model (hazard ratio 2.99; 95% confidence interval 1.04, 8.64)., Conclusions: In MHD patients, OEA and PEA are significantly correlated with variables related to lipid metabolism and body mass. Additionally, higher serum levels of PEA are associated with mortality risk. Future studies are needed to examine the potential mechanisms responsible for these findings and their clinical implications., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Background: Higher estimated glomerular filtration rate (eGFR) at dialysis initiation, known as earlier start of dialysis, is often a surrogate of poor outcomes including higher mortality. We hypothesized that earlier dialysis initiation is associated with a faster decline in residual kidney function (RKF), which is also associated with higher mortality among incident hemodialysis (HD) patients., Methods: In a cohort of 4911 incident HD patients who initiated HD over a 5-year period (July 2001 to June 2006), we examined the trajectories of RKF, ascertained by renal urea clearance (KRU), over 2 years after HD initiation across strata of eGFR at HD initiation using case-mix adjusted linear mixed-effect models. We then investigated the association between annual change in RKF and mortality using Cox proportional hazard models., Results: The median (interquartile range) baseline KRU was 2.20 (1.13-3.63)  mL/min/1.73 m2. The decline of KRU was faster in patients who initiated HD at higher eGFR. The relative changes with 95% confidence intervals (CIs) in KRU at 1 year after HD initiation were -1.29 (-1.28 to -1.30), -1.17 (-1.16 to -1.18), -1.11 (-1.10 to -1.12) and -0.78 (-0.78 to -0.79)  mL/min/1.73 m2 in the eGFR categories of ≥10, 8-<10, 6-<8 and <6 mL/min/1.73 m2, respectively. The faster decline of KRU at 1 year was associated with higher all-cause mortality (reference: ≥0 mL/min/1.73 m2): hazard ratios (95% CIs) for change in KRU of -1.5 to <0, -3 to less than -1.5 and less than -3 mL/min/1.73 m2 were 1.20 (1.03-1.40), 1.42 (1.17-1.72) and 1.88 (1.47-2.40), respectively., Conclusions: The faster decline of RKF happens with earlier dialysis initiation and is associated with higher all-cause mortality., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

For patients on dialysis, hospitalizations remain a major risk factor for mortality and morbidity. We use data from a large national database, United States Renal Data System, to model time-varying effects of hospitalization risk factors as functions of time since initiation of dialysis. To account for the three-level hierarchical structure in the data where hospitalizations are nested in patients and patients are nested in dialysis facilities, we propose a multilevel mixed effects varying coefficient model (MME-VCM) where multilevel (patient- and facility-level) random effects are used to model the dependence structure of the data. The proposed MME-VCM also includes multilevel covariates, where baseline demographics and comorbidities are among the patient-level factors, and staffing composition and facility size are among the facility-level risk factors. To address the challenge of high-dimensional integrals due to the hierarchical structure of the random effects, we propose a novel two-step approximate EM algorithm based on the fully exponential Laplace approximation. Inference for the varying coefficient functions and variance components is achieved via derivation of the standard errors using score contributions. The finite sample performance of the proposed estimation procedure is studied through simulations., (© 2019 The International Biometric Society.)

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: Congenital anomalies of the kidney and urinary tract (CAKUT) is associated with a slower progression to end-stage renal disease (ESRD) in pre-dialysis patients. However, little is known about the associated mortality risks after transitioning to dialysis., Methods: This retrospective cohort study included 0-21 year-old incident dialysis patients from the United States Renal Data System starting dialysis between 1995 and 2016. We examined the association of CAKUT vs. non-CAKUT with all-cause mortality, using Cox regression adjusted for case mix variables. We also examined the mortality risk associated with 14 non-CAKUT vs. CAKUT ESRD etiologies and under stratification by estimated glomerular filtration rate (eGFR)., Results: Among 25,761 patients, the median (interquartile range) age was 17 (11-19) years, and 4780 (19%) had CAKUT. CAKUT was associated with lower mortality, with an adjusted hazard ratio (aHR) of 0.72 (95%CI, 0.64-0.81) (reference: non-CAKUT). In age-stratified analyses, CAKUT vs. non-CAKUT aHRs (95%CI) were 0.66 (0.54-0.80), 0.56 (0.39-0.80), 0.66 (0.50-0.86), and 0.97 (0.80-1.18) among patients < 6, 6-< 13, 13-< 18, and ≥ 18 years at dialysis initiation, respectively. Among non-CAKUT ESRD etiologies, the risk of mortality associated with primary glomerulonephritis (aHR, 0.93; 95%CI 0.80-1.09) and focal segmental glomerulosclerosis (aHR, 0.89; 95%CI, 0.75-1.04) were comparable or slightly lower compared to CAKUT, whereas most other primary causes were associated with higher mortality risk. While the CAKUT group had lower mortality risk compared to the non-CAKUT group patients with eGFR ≥5 mL/min/1.73m 2 , CAKUT was associated with higher mortality in patients with eGFR < 5 mL/min/1.73 m 2 ., Conclusions: CAKUT is associated with lower mortality among children < 18 years old, but showed comparable mortality with non-CAKUT among patients ≥ 18 years old. ESRD etiology should be considered in risk assessment for children initiating dialysis.

Profiling analysis aims to evaluate health care providers, such as hospitals, nursing homes, or dialysis facilities, with respect to a patient outcome. Previous profiling methods have considered binary outcomes, such as 30-day hospital readmission or mortality. For the unique population of dialysis patients, regular blood works are required to evaluate effectiveness of treatment and avoid adverse events, including dialysis inadequacy, imbalance mineral levels, and anemia among others. For example, anemic events (when hemoglobin levels exceed normative range) are recurrent and common for patients on dialysis. Thus, we propose high-dimensional Poisson and negative binomial regression models for rate/count outcomes and introduce a standardized event ratio measure to compare the event rate at a specific facility relative to a chosen normative standard, typically defined as an "average" national rate across all facilities. Our proposed estimation and inference procedures overcome the challenge of high-dimensional parameters for thousands of dialysis facilities. Also, we investigate how overdispersion affects inference in the context of profiling analysis. The proposed methods are illustrated with profiling dialysis facilities for recurrent anemia events., (© 2020 John Wiley & Sons, Ltd.)

Rationale & Objective: Patients receiving twice-weekly or less-frequent hemodialysis (HD) may need to undergo higher ultrafiltration rates (UFRs) to maintain acceptable fluid balance. We hypothesized that higher UFRs are associated with faster decline in residual kidney function (RKF) and a higher rate of mortality., Study Design: Retrospective cohort study., Setting & Participants: 1,524 patients with kidney failure who initiated maintenance HD at a frequency of twice or less per week for at least 6 consecutive weeks at some time between 2007 and 2011 and for whom baseline data for UFR and renal urea clearance were available., Predictor: Average UFR during the first patient-quarter during less-frequent HD (<6, 6-<10, 10-<13, and≥13mL/h/kg)., Outcome: Time to all-cause and cardiovascular death, slope of decline in RKF during the first year after initiation of less-frequent HD (with slopes above the median categorized as rapid decline)., Analytical Approach: Cox proportional hazards regression for time to death and logistic regression for the analysis of rapid decline in RKF., Results: Among 1,524 patients, higher UFR was associated with higher all-cause mortality; HRs were 1.43 (95% CI, 1.09-1.88), 1.51 (95% CI, 1.08-2.10), and 1.76 (95% CI, 1.23-2.53) for UFR of 6 to<10, 10 to<13, and≥13mL/h/kg, respectively (reference: UFR < 6mL/h/kg). Higher UFR was also associated with higher cardiovascular mortality. Baseline RKF modified the association between UFR and mortality; the association was attenuated among patients with renal urea clearance≥5mL/min/1.73m 2 . Higher UFR had a graded association with rapid decline in RKF; ORs were 1.73 (95% CI, 1.18-2.55), 1.89 (95% CI, 1.12-3.17), and 2.75 (95% CI, 1.46-5.18) at UFRs of 6 to<10, 10 to<13, and≥13mL/h/kg, respectively (reference: UFR < 6mL/h/kg)., Limitations: Residual confounding from unobserved differences across exposure categories., Conclusions: Higher UFR was associated with worse outcomes, including shorter survival and more rapid loss of RKF, among patients receiving regular HD treatments at a frequency of twice or less per week., (Published by Elsevier Inc.)

Background: Arteriovenous fistulas (AVFs) are the preferred vascular access type in most hemodialysis patients. However, the optimal vascular access type in octogenarians and older (≥80 years) hemodialysis patients remains widely debated given their limited life expectancy and lower AVF maturation rates., Methods: Among incident hemodialysis patients receiving care in a large national dialysis organization during 2007-2011, we examined patterns of vascular access type conversion in 1 year following dialysis initiation in patients <80 versus ≥80 years of age. Among a subcohort of patients ≥80 years of age, we examined the association between vascular access type conversion and mortality using multivariable survival models., Results: In the overall cohort of 100 804 patients, the prevalence of AVF/arteriovenous graft (AVG) as the primary vascular access type increased during the first year of hemodialysis, but plateaued thereafter. Among 8356 patients ≥80 years of age and treated for >1 year, those with initial AVF/AVG use and placement of AVF from a central venous catheter (CVC) had lower mortality compared with patients with persistent CVC use. When the reference group was changed to patients who had AVF placement from a CVC in the first year of dialysis, those with initial AVF use had similar mortality. A longer duration of CVC use was associated with incrementally worse survival., Conclusions: Among incident hemodialysis patients ≥80 years of age, placement of an AVF from a CVC within the first year of dialysis had similar mortality compared with initial AVF use. Our data suggest that initial CVC use with later placement of an AVF may be an acceptable option among elderly hemodialysis patients., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Abnormalities of mineral bone disorder (MBD) parameters have been suggested to be associated with poor renal outcome in predialysis patients. However, the impact of those parameters on decline in residual kidney function (RKF) is uncertain among incident hemodialysis (HD) patients. We performed a retrospective cohort study in 13,772 patients who initiated conventional HD during 2007 to 2011 and survived 6 months of dialysis. We examined the association of baseline serum phosphorus, calcium, intact parathyroid hormone (PTH), and alkaline phosphatase (ALP) with a decline in RKF. Decline in RKF was assessed by estimated slope of renal urea clearance (KRU) over 6 months from HD initiation. Our cohort had a mean ± SD age of 62 ± 15 years; 64% were men, 57% were white, 65% had diabetes, and 51% had hypertension. The median (interquartile range [IQR]) baseline KRU level was 3.4 (2.0, 5.2) mL/min/1.73 m 2 . The median (IQR) estimated 6-month KRU slope was -1.47 (-2.24, -0.63) mL/min/1.73 m 2 per 6 months. In linear regression models, higher phosphorus categories were associated with a steeper 6-month KRU slope compared with the reference category (phosphorus 4.0 to <4.5 mg/dL). Lower calcium and higher intact PTH and ALP categories were also associated with a steeper 6-month KRU slope compared with their respective reference groups (calcium 9.2 to <9.5 mg/dL; intact PTH 150 to <250 pg/mL; ALP <60 U/L). The increased number of parameter abnormalities had an additive effect on decline in RKF. Abnormalities of MBD parameters including higher phosphorus, intact PTH, ALP and lower calcium levels were independently associated with decline in RKF in incident HD patients. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Background: Mortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (MHD) remains exceptionally high. While traditional risk factors such as obesity are paradoxically associated with better survival, nontraditional risk factors including cachexia increase the likelihood of poor outcomes. There is accumulating evidence that the endocannabinoid (ECB) system plays a major role in energy preservation and storage, factors which can prevent the deleterious effects of cachexia. Hence, in this study, we evaluated the association of circulating ECB levels with mortality in MHD patients., Methods: Serum concentrations of anandamide (AEA) and 2-arachidonoyl-sn-glycerol (2-AG), major ECB ligands, were measured in MHD patients. Their correlation with various clinical/laboratory indices and association with 12-month all-cause mortality were examined., Results: Serum 2-AG levels positively correlated with body mass index, serum triglycerides and body anthropometric measures. Meanwhile, serum AEA levels correlated positively with serum interleukin-6, and negatively with serum very low-density lipoprotein levels. While increased serum 2-AG levels were associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.52, 95% CI 0.28-0.98), there was no clear association between serum AEA levels and mortality (HR 0.91, 95% CI 0.48-1.72)., Conclusions: In MHD patients, the circulating levels of ECB ligand, 2-AG, may play an important role in determining body mass and risk of mortality. These observations were unique to 2-AG as similar findings were not obtained with serum AEA. Future studies need to investigate the mechanisms responsible for these associations and examine the modulation of the ECB system as a potential target for therapy in ESRD., (© 2020 S. Karger AG, Basel.)

Objective: Incremental hemodialysis (HD) is a strategy utilized to gradually intensify dialysis among patients with incident end-stage renal disease. However, there are scarce data about which patients' clinic status changes by increasing treatment frequency., Methods: We retrospectively examined statistically de-identified data from 569 patients who successfully transitioned from twice- to thrice-weekly HD (2007-2011) and compared the differences in monthly-averaged values of hemodynamic and laboratory indices during the 3 months before and after the transition with the values at 1 month prior to transition serving as the reference., Results: At 3 months after transitioning from twice- to thrice-weekly HD, ultrafiltration volume decreased by 0.5 (95% CI 0.3-0.6) L/session among 189 patients (33%) with weekly interdialytic weight gain (IDWG) ≥5.4 kg/week, and increased by 0.4 (95% CI 0.3-0.5) L/session among 186 patients (33%) with weekly IDWG <3.3 kg/week. Weekly IDWG consistently increased after the transition irrespective of baseline values (1.7 [95% CI 1.5-1.9] kg/week). Pre-HD systolic blood pressure (SBP) decreased by 12 (95% CI 9-14) mm Hg among 177 patients (31%) with baseline pre-HD SBP ≥160 mm Hg, which coincided with a decreasing trend in post-HD body weight (1.3 [95% CI 0.8-1.7] kg)., Discussion: In conclusion, patients who increased HD frequency from twice to thrice weekly treatment experienced increased weekly IDWG and better pre-HD SBP control with lower post-HD body weight., (© 2020 S. Karger AG, Basel.)

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.)

Objectives of Review: Protein-energy wasting (PEW) is a state of disordered catabolism resulting from metabolic and nutritional derangements in chronic disease states. Patients with chronic kidney disease (CKD), and end-stage renal disease (ESRD) in particular, have muscle wasting, sarcopenia, and cachexia that contribute to frailty and morbidity. Moreover, reverse epidemiology findings have strongly linked PEW with mortality in CKD and ESRD. Updated Findings: The malnutrition-inflammation score (KALANTAR Score) provides a useful tool to predict nutritional risk. A stronger focus on renal nutrition in renal patients is needed to attenuate cachexia and muscle loss. Malnutrition is a far greater threat in patients with renal disease than obesity, which means dietary counseling needs to be tailored to reflect this observation. The need to achieve optimal caloric intake is compounded by the need to limit excess protein intake in CKD, resulting in the need for energy supplementation to avoid PEW. Preventing PEW is the most pressing clinical concern in CKD/ESRD. Other nutritional issues to reckon in renal disease include the need to normalize serum bicarbonate to manage acidosis, uric acid control, and phosphorous control in CKD and ESRD. Exercise maybe beneficial, but further work is needed to prove a conclusive benefit via a randomized trial. Summary: PEW prevention is an integral part of renal nutrition and is of paramount importance given the obesity paradox. Integrative approaches by physicians and dieticians are needed to take a holistic view of a patient's diet beyond just control of particular laboratory parameters., (© 2019 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.)

Context: In end-stage renal disease (ESRD), serum high-density lipoprotein cholesterol (HDL-C) level is not an accurate predictor of mortality, partly because it does not necessarily correlate with indices of HDL function. Paraoxonase (PON) is a major enzyme constituent of HDL and a key component of HDL antioxidant activity. Apolipoprotein A-I (Apo A-1) is the core HDL structural protein that plays a major role in various aspects of HDL function., Objective: We sought to examine PON activity and Apo A-I levels in patients with ESRD vs healthy controls., Design and Setting: PON/arylesterase activity was measured in 499 patients with maintenance hemodialysis (MHD) and 24 healthy controls with similar distributions of age, sex, and race/ethnicity. Serum acrolein-modified Apo A-I was measured in 30 patients with MHD and 10 healthy controls., Main Outcome Measures: Multilevel Cox models were used to assess associations among PON activity, Apo A-I, and HDL-C levels with 12-month all-cause mortality., Results: PON activity was significantly lower in patients with MHD vs controls. Furthermore, acrolein-modified Apo A-I levels were higher in patients with MHD vs controls. In fully adjusted models, high PON activity was associated with lower 12-month mortality, whereas no difference of mortality risk was observed across HDL-C levels. The combination of high PON and low Apo A-I compared with low PON and low Apo A-I was associated with lower mortality risk., Conclusions: In patients with MHD, PON activity had a stronger association with 12-month mortality than HDL-C. Future studies are needed to examine the role of these markers as potential diagnostic and therapeutic tools in ESRD., (Copyright © 2019 Endocrine Society.)

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.)

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.)

Rationale & Objective: The association of estimated glomerular filtration rate (eGFR) at dialysis therapy initiation with mortality among adult dialysis patients has been greatly debated, with some studies showing no benefit from early dialysis therapy initiation. However, this association has not been well investigated in pediatric dialysis patients. The objective of this study was to evaluate the mortality risk associated with eGFR at dialysis therapy initiation in children and adolescents with kidney failure., Study Design: Retrospective cohort study., Setting & Participants: 9,963 incident dialysis patients aged 1 to 17 years in the US Renal Data System registry (1995-2016)., Predictor: eGFRs at dialysis therapy initiation calculated using the pediatric-specific bedside Schwartz equation (<5, 5-<7, 7-<9, 9-<12, and ≥12mL/min/1.73m 2 )., Outcome: Time to all-cause death., Analytical Approach: Cox proportional hazards regression adjusted for case-mix variables, height, body mass index, hemoglobin level, and serum albumin level., Results: Median eGFR was 7.8 (IQR, 5.6-10.5) mL/min/1.73m 2 and median age was 13 (IQR, 9-16) years. 696 deaths were observed during the median follow-up of 1.4 (IQR, 0.7-2.7) years, and overall crude mortality rate was 31 per 1,000 patient-years. There appeared to be a trend toward higher mortality risk across higher eGFRs at dialysis therapy initiation. Compared with eGFRs of 7 to <9mL/min/1.73m 2 , eGFRs <5 and ≥12mL/min/1.73m 2 were associated with lower and higher mortality, with adjusted HRs of 0.57 (95% CI, 0.43-0.74) and 1.31 (95% CI, 1.05-1.65), respectively. In age-stratified analysis, there were consistent relationships among patients 6 years and older while the eGFR-mortality association was attenuated among patients younger than 6 years (P interaction  = 0.002)., Limitations: Possible errors in eGFRs due to methods for serum creatinine measurement. Unmeasured confounders related to eGFR at dialysis therapy initiation., Conclusions: Higher eGFR at dialysis therapy initiation was associated with higher mortality risk. Further studies of eGFR at initiation are needed in pediatric dialysis patients, especially among those younger than 6 years., (Copyright © 2019. Published by Elsevier Inc.)

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.)

Background: Observational studies show that African American (AA) dialysis patients have longer survival than European Americans. We hypothesized that apolipoprotein L1 (APOL1) genetic variation, associated with nephropathy in AAs, contributes to the survival advantage in AA dialysis patients., Methods: We examined the association between race and mortality among 37,097 adult dialysis patients, including 54% AAs and 46% European Americans from a large dialysis organization (entry period from July 2001 to June 2006, follow-up through June 2007), within each cause of end-stage renal disease (ESRD) category associated with APOL1 renal risk variants using Cox proportional hazard models., Results: AA dialysis patients had numerically lower mortality than their European American counterparts for all causes of ESRD. The mortality reduction among AAs compared to European Americans was statistically significant in patients with ESRD attributed to diabetes mellitus, hypertension, and APOL1-enriched glomerulonephritis (GN) (HR [95% CI]: 0.69 [0.66-0.72], 0.73 [0.68-0.79], and 0.89 [0.79-0.99], respectively); these are conditions in which APOL1 variants promote kidney disease. By contrast, the significant survival advantage of AA dialysis patients was not observed in patients with ESRD attributed to other kidney disease (including polycystic kidney disease, interstitial nephritis, and pyelonephritis) and other GN, which are not associated with APOL1 variants., Conclusions: These data suggest the hypothesis that the relative survival advantage of AA dialysis patients may be related to APOL1 variation. Further large population-based genetic studies are required to test this hypothesis., (© 2019 Published by S. Karger AG, Basel.)

Background/aims: Anemia is common in patients with advanced chronic kidney disease (CKD). A proportion of patients present with macrocytic anemia, manifested by elevated mean corpuscular volume (MCV), which has been associated with worse outcomes in CKD patients. However, it is unknown whether elevated MCV is associated with higher mortality risk in incident hemodialysis (HD) patients., Methods: This retrospective observational cohort study examined all-cause, cardiovascular, and infectious mortality associations with both baseline and time-varying MCV in 109,501 incident HD patients using Cox proportional hazards models with 3 levels of hierarchical multivariable adjustment. Odds ratios of high versus low baseline MCV were evaluated using logistic regression., Results: The mean age of patients was 65 ± 15 (standard deviation) years and the cohort was 44% female, 58% diabetic, and 31% African American. Higher MCV was associated with older age, female sex, non-Hispanic White race-ethnicity, alcohol consumption, and having a decreased albumin or protein intake. Patients with higher MCV levels (> 98 fL) had a higher all-cause, cardiovascular, and infectious mortality risk in both baseline and time varying models, and across all levels of adjustment. In the fully adjusted models, compared to a reference of MCV 92-< 94 fL, patients with a baseline MCV > 100+ fL had a 28% higher risk of all-cause mortality (hazard ratio [HR] 1.28, 95% CI 1.22-1.34), 27% higher risk of cardiovascular mortality (HR 1.27, 95% CI 1.18-1.36), and 18% higher risk of infectious mortality (HR 1.18, 95% CI 1.02-1.38). Associations of higher MCV with these adverse outcomes persisted across all examined subgroups of clinical characteristics., Conclusions: Higher MCV was associated with higher all-cause, cardiovascular, and infectious mortality in HD patients. Further investigation is necessary to understand the underlying nature of the observed association., (© 2019 S. Karger AG, Basel.)

For chronic dialysis patients, a unique population requiring continuous medical care, methodologies to monitor patient outcomes, such as hospitalizations, over time, after initiation of dialysis, are of particular interest. Contributing to patient hospitalizations is a number of multilevel covariates such as demographics and comorbidities at the patient level and staffing composition at the dialysis facility level. We propose a varying coefficient model for multilevel risk factors (VCM-MR) to study the time-varying effects of covariates on patient hospitalization risk as a function of time on dialysis. The proposed VCM-MR also includes subject-specific random effects to account for within-subject correlation and dialysis facility-specific fixed effect varying coefficient functions to allow for the modeling of flexible time-varying facility-specific risk trajectories. An approximate EM algorithm and an iterative Newton-Raphson approach are proposed to address the challenge of estimation of high-dimensional parameters (varying coefficient functions) for thousands of dialysis facilities in the United States. The proposed modeling allows for comparisons between time-varying effects of multilevel risk factors as well as testing of facility-specific fixed effects. The method is applied to model hospitalization risk using the rich hierarchical data available on dialysis patients initiating dialysis between January 1, 2006 and December 31, 2008 from the United States Renal Data System, a large national database, where 331 443 hospitalizations over time are nested within patients, and 89 889 patients are nested within 2201 dialysis facilities. Patients are followed-up until December 31, 2013, where the follow-up time is truncated five years after the initiation of dialysis. Finite sample properties are studied through extensive simulations., (© 2018 John Wiley & Sons, Ltd.)

Rationale & Objective: Diabetic patients with declining kidney function are at heightened risk for hypoglycemia. We sought to determine whether hypoglycemia-related hospitalizations in the interval before dialysis therapy initiation are associated with post-end-stage renal disease (ESRD) mortality among incident patients with ESRD with diabetes., Study Design: Observational cohort study., Setting & Participants: US veterans from the national Veterans Affairs database with diabetes and chronic kidney disease transitioning to dialysis therapy from October 2007 to September 2011., Exposure: Hypoglycemia-related hospitalizations during the pre-ESRD period and antidiabetic medication regimens., Outcome: The outcome of post-ESRD all-cause mortality was evaluated relative to pre-ESRD hypoglycemia. The outcome of pre-ESRD hypoglycemia-related hospitalization was evaluated relative to antidiabetic medication regimens., Analytic Approach: We examined whether the occurrence and frequency of pre-ESRD hypoglycemia-related hospitalizations are associated with post-ESRD mortality using Cox regression models adjusted for case-mix covariates. In a subcohort of patients prescribed 0 to 2 oral antidiabetic drugs and/or insulin, we examined the 12 most commonly prescribed antidiabetic medication regimens and risk for pre-ESRD hypoglycemia-related hospitalization using logistic regression models adjusted for case-mix covariates., Results: Among 30,156 patients who met eligibility criteria, the occurrence of pre-ESRD hypoglycemia-related hospitalization(s) was associated with higher post-ESRD mortality risk: adjusted HR (aHR), 1.25; 95% CI, 1.17-1.34 (reference group: no hypoglycemia hospitalization). Increasing frequency of hypoglycemia-related hospitalizations was independently associated with incrementally higher mortality risk: aHRs of 1.21 (95% CI, 1.12-1.30), 1.47 (95% CI, 1.19-1.82), and 2.07 (95% CI, 1.46-2.95) for 1, 2, and 3 or more hypoglycemia-related hospitalizations, respectively (reference group: no hypoglycemia hospitalization). Compared with patients who were prescribed neither oral antidiabetic drugs nor insulin, medication regimens that included sulfonylureas and/or insulin were associated with higher risk for hypoglycemia., Limitations: Residual confounding cannot be excluded., Conclusions: Among incident patients with ESRD with diabetes, a dose-dependent relationship between frequency of pre-ESRD hypoglycemia-related hospitalizations and post-ESRD mortality was observed. Further study of diabetic management strategies that prevent hypoglycemia as patients with chronic kidney disease transition to ESRD are warranted., (Copyright © 2018 National Kidney Foundation, Inc. All rights reserved.)

In the United States, end-stage renal disease patients receiving hemodialysis have an exceedingly high risk of sudden cardiac death (SCD), accounting for 29% of death events, likely relating to their uremic milieu, recurring exposure to fluid and electrolyte fluxes, and underlying cardiovascular pathology. Furthermore, epidemiologic studies have shown that SCD events, as well as mortality and hospitalizations, occur most frequently on the first dialysis day after the long interdialytic gap, suggesting that abrupt fluctuations in the accumulation and removal of electrolytes, fluid, and uremic toxins over the dialysis cycle may be contributory. Some population-based observational studies have suggested that lower dialysate potassium concentrations appear to be associated with a heightened risk of postdialysis cardiac arrest in hemodialysis patients, although the optimal serum-to-dialysate potassium gradient remains unclear. Some observational studies have suggested that low dialysate calcium concentrations and high serum-to-dialysate calcium gradients may predispose patients to SCD. There is ongoing controversy about an association between higher dialysate bicarbonate concentrations and higher risk of cardiac arrest, likely owing to confounding by indication. Some observational studies also have shown that large interdialytic weight gains, fluid retention, and high ultrafiltration rates are linked with higher risk of SCD and mortality. However, there remains considerable controversy regarding the pros and cons of designating a specific upper ultrafiltration limit with extended treatment times as a clinical practice measure, and further studies are needed to define the optimal tools, metrics, targets, and implementation measures for volume control in the hemodialysis population. In this review, we highlight the epidemiology and pathophysiology of how specific aspects of the hemodialysis procedure may relate to the risk of SCD, as well as preventative strategies and future research directions that can address this risk., (Copyright © 2018. Published by Elsevier Inc.)

Background: Both dialysis dose and residual kidney function (RKF) contribute to solute clearance and are associated with outcomes in hemodialysis patients. We hypothesized that the association between dialysis dose and mortality is attenuated with greater RKF., Methods: Among 32 251 incident hemodialysis patients in a large US dialysis organization (2007-11), we examined the interaction between single-pool Kt/V (spKt/V) and renal urea clearance (rCLurea) levels in survival analyses using multivariable Cox proportional hazards regression model., Results: The median rCLurea and mean baseline spKt/V were 3.06 [interquartile range (IQR) 1.74-4.85] mL/min/1.73 m2 and 1.32 ± 0.28, respectively. A total of 7444 (23%) patients died during the median follow-up of 1.2 years (IQR 0.5-2.2 years) with an incidence of 15.4 deaths per 100 patient-years. The Cox model with adjustment for case-mix and laboratory variables showed that rCLurea modified the association between spKt/V and mortality (Pinteraction = 0.03); lower spKt/V was associated with higher mortality among patients with low rCLurea (i.e. <3  mL/min/1.73 m2) but not among those with higher rCLurea. The adjusted mortality hazard ratios (aHRs) and 95% confidence intervals of the low (<1.2) versus high (≥1.2) spKt/V were 1.40 (1.12-1.74), 1.21 (1.10-1.33), 1.06 (0.98-1.14), and 1.00 (0.93-1.08) for patients with rCLurea of 0.0, 1.0, 3.0 and 6.0 mL/min/1.73 m2, respectively., Conclusions: Incident hemodialysis patients with substantial RKF do not exhibit the expected better survival at higher hemodialysis doses. RKF levels should be taken into account when deciding on the dose of dialysis treatment among incident hemodialysis patients.

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 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.)

Launched in 2016, the overarching goal of the Precision Medicine Initiative is to promote a personalized approach to disease management that takes into account an individual's unique underlying biology and genetics, lifestyle, and environment, in lieu of a one-size-fits-all model. The concept of precision medicine is pervasive across many areas of nephrology and has been particularly relevant to the care of advanced chronic kidney disease patients transitioning to end-stage kidney disease (ESKD). Given many uncertainties surrounding the optimal transition of incident ESKD patients to dialysis and transplantation, as well as the high mortality rates observed during this delicate transition period, there is a pressing urgency for implementing precision medicine in the management of this population. Although the traditional paradigm has been to commence incident hemodialysis patients on a 3 times/week treatment regimen, largely driven by adequacy targets, there has been growing recognition that alternative treatment regimens (ie, incremental hemodialysis) may be preferred among certain subpopulations when taking into consideration factors such as patients' residual kidney function, volume status fluctuations, symptoms, and preferences. In this review, we examine the origins of current practices in how dialysis is initiated among incident ESKD patients; incremental dialysis therapy as a dynamic and patient-centric approach that is tailored to patients' unique characteristics; recent data on the incremental hemodialysis regimen and outcomes; and future research directions using a precision nephrology approach to ESKD management with the potential to develop novel approaches, tools, and collaborative efforts to improve the health, well-being, and survival of this population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

While many patients have substantial residual kidney function (RKF) when initiating hemodialysis (HD), most patients with end stage renal disease in the United States are initiated on 3-times per week conventional HD regimen, with little regard to RKF or patient preference. RKF is associated with many benefits including survival, volume control, solute clearance, and reduced inflammation. Several strategies have been recommended to preserve RKF after HD initiation, including an incremental approach to HD initiation. Incremental HD prescriptions are personalized to achieve adequate volume control and solute clearance with consideration to a patient's endogenous renal function. This allows the initial use of less frequent and/or shorter HD treatment sessions. Regular measurement of RKF is important because HD frequency needs to be increased as RKF inevitably declines. We narratively review the results of 12 observational cohort studies of twice-weekly compared to thrice-weekly HD. Incremental HD is associated with several benefits including preservation of RKF as well as extending the event-free life of arteriovenous fistulas and grafts. Patient survival and quality of life, however, has been variably associated with incremental HD. Serious risks must also be considered, including increased hospitalization and mortality perhaps related to fluid and electrolyte shifts after a long interdialytic interval. On the basis of the above literature review, and our clinical experience, we suggest patient characteristics which may predict favorable outcomes with an incremental approach to HD. These include substantial RKF, adequate volume control, lack of significant anemia/electrolyte imbalance, satisfactory health-related quality of life, low comorbid disease burden, and good nutritional status without evidence of hypercatabolism. Clinicians should engage patients in on-going conversations to prepare for incremental HD initiation and to ensure a smooth transition to thrice-weekly HD when needed., (© 2018 Wiley Periodicals, Inc.)

Background: There is accumulating evidence that serum levels of non-high-density lipoprotein cholesterol (non-HDL-C) are a more accurate predictor of cardiovascular outcomes when compared with low-density lipoprotein cholesterol. However, we recently found that higher serum concentrations of triglycerides are associated with better outcomes in patients undergoing hemodialysis. Therefore, we hypothesized that the association of serum levels of non-HDL-C (which includes triglyceride-rich lipoproteins) with outcomes may also be different in patients undergoing hemodialysis when compared with other patient populations., Methods and Results: We studied the association of baseline and time-dependent serum levels of non-HDL-C with all-cause and cardiovascular mortality using Cox proportional hazard regression models in a nationally representative cohort of 50 118 patients undergoing incident hemodialysis from January 1, 2007, to December 31, 2011. In time-dependent models adjusted for case mix and surrogates of malnutrition and inflammation, a graded inverse association between non-HDL-C level and mortality was demonstrated with hazard ratios (95% confidence intervals) of the lowest (<60 mg/dL) and highest (≥160 mg/dL) categories: 1.88 (1.72-2.06) and 0.73 (0.64-0.83) for all-cause mortality and 2.07 (1.78-2.41) and 0.75 (0.60-0.93) for cardiovascular mortality, respectively (reference, 100-115 mg/dL). In analyses using baseline values, non-HDL-C levels <100 mg/dL were also associated with significantly higher mortality risk across all levels of adjustment. Similar associations were found when evaluating non-HDL/HDL cholesterol ratio and mortality, with the highest all-cause and cardiovascular mortality being observed in patients with decreased non-HDL/HDL-C ratio (<2.5)., Conclusions: Contrary to the general population, decrements in non-HDL-C and non-HDL/HDL cholesterol ratio were paradoxically associated with increased all-cause and cardiovascular mortality in patients undergoing incident hemodialysis. The underlying mechanisms responsible for these associations await further investigation., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Patients' experience of care (PEC) is as an important dimension in quality of care. As a distinct entity from patient satisfaction and patient health-related quality of life, PEC is defined as patients' perceptions of the range of interactions they have with the health care system, including care from providers, facilities, and health plans. While traditionally PEC may be ascertained via informal assessments, in recent years, especially in the United States, there has been a shift towards standardized surveillance of PEC amongst dialysis patients in order to: (1) set a normative expectation regarding the importance of PEC; (2) standardize the components of patients' experience that are assessed to minimize potential "blind spots"; (3) provide a direct "voice" to the patient in communicating perceptions of their care; (4) facilitate comparisons of quality across facilities; and (5) broaden accountability for PEC to the entire multidisciplinary dialysis care team. In this review, we will discuss the significance of PEC as a quality of care metric in dialysis patients; the history of PEC assessment across other health care arenas; the development of the In-Center Hemodialysis Consumer Assessment of Healthcare Provider and Systems survey as a means to standardize PEC assessment among US dialysis patients; experiences in PEC assessment across international dialysis populations; and future areas of research needed to refine the ascertainment of PEC and its impact upon patient outcomes.

Background: Elevated serum high-density lipoprotein cholesterol (HDL-C) has not been associated with better cardiovascular (CV) and all-cause mortality in hemodialysis patients. However, the association between change in HDL over time and mortality has not been fully examined., Objective: In a nationally representative cohort of incident hemodialysis patients who had available HDL data at baseline and 6 months after dialysis initiation, we studied the association of change in HDL-C during the first 6 months of dialysis with all-cause and CV mortality., Methods: Associations between HDL-C change and mortality were determined in Cox proportional hazard regression models with adjustment for multiple variables., Results: In case-mix models, there was a J-shaped association between change in HDL-C and mortality, such that quartiles 1 (<-5 mg/dL) and 4 (≥7 mg/dL) were each associated with higher all-cause (hazard ratio, 1.32 [95% confidence interval, 1.21-1.45] and 1.09 [1.01-1.18]) and CV (1.28 [1.06-1.55] and 1.23 [1.04-1.45]) death risk, respectively. In fully adjusted models that included indices of malnutrition and inflammation, the higher death risk observed in the lowest quartile was attenuated, whereas the highest quartile continued to demonstrate significantly higher all-cause (1.11 [1.02-1.20]) and CV mortality (1.15 [1.00-1.32]). These associations persisted across various subgroups., Conclusions: Although malnutrition and inflammation may explain the increased risk for mortality in patients with decreasing serum HDL-C concentrations over time, these indices do not mitigate the elevated risk in patients with rising serum HDL-C. We found that increasing serum HDL-C over time is paradoxically associated with worse outcomes in incident hemodialysis patients., (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.)

Background: Incident hemodialysis patients have a high mortality risk within the first months after dialysis initiation. Pre-end-stage renal disease (ESRD) factors like anemia management may impact early post-ESRD outcomes. Therefore, we evaluated the impact of pre-ESRD hemoglobin (Hgb) and pre-ESRD Hgb slope on post-ESRD mortality and hospitalization outcomes., Methods: The study included 31,472 veterans transitioning to ESRD. Using Cox and negative binomial regression models, we evaluated the association of pre-ESRD Hgb and Hgb slope with 12-month post-ESRD all-cause and cardiovascular mortality and hospitalization rates using 4 levels of hierarchical multivariable adjustment, including erythropoietin use and kidney decline in slope models., Results: The cohort was 2% female, 30% African-American, and on average 68 ± 11 years old. Compared to Hgb 10-< 11 g/dL, both low (< 10 g/dL) and high (≥12 g/dL) levels were associated with higher all-cause mortality after full adjustment (HR 1.25 [95% CI 1.15-1.35] and 1.09 [95% CI 1.02-1.18], respectively). Similarly, Hgb exhibited a U-shaped association with CV mortality, while only lower Hgb was associated with a higher hospitalization rate. Neither an annual pre-ESRD decline in Hgb nor increase was associated with higher post-ESRD mortality risk after adjustment for kidney decline. However, we observed a modest J-shaped association between pre-ESRD Hgb slope and post-ESRD hospitalization rate., Conclusions: Lower and higher pre-ESRD Hgb levels are associated with a higher risk of early post-ESRD mortality, while there was no association between the pre-ESRD slope and mortality. An increase in pre-ESRD Hgb slope was associated with higher risk of post-ESRD hospitalization. Additional studies aimed at anemia management prior to ESRD transition are warranted., (© 2018 S. Karger AG, Basel.)

Background: The population of elderly end-stage renal disease patients initiating dialysis is rapidly growing. Although longer treatment is supposed to benefit for hemodialysis (HD) patients through more solute clearance and slower fluid removal, it is not yet clear how treatment session length affects mortality risk in octogenarians and nonagenarians., Methods: In a cohort of 112,026 incident HD patients between 2007 and 2011, we examined the association of treatment session length with all-cause mortality, adjusting for demographics and comorbid conditions. We also used restricted spline functions for age to evaluate continuous changes in the association of short (< 210 min) and extended (≥240 min) HD treatment (vs. 210 to < 240 min) with all-cause mortality over continuous age., Results: During the first 91 days of dialysis, patients aged ≥80 years tended to have the lowest treatment session length (median [interquartile range] 211 [193-230] min, r > 0.5). Longer treatment was associated with better survival in patients < 65 and 65 to < 80 years but not in octogenarians/nonagenarians. The association of extended treatment (≥240 min) with better survival was attenuated across age and not significant among patients aged ≥80 years with a hazard ratio of 1.10 (95% CI 0.99-1.20). Shorter treatment sessions (< 210 min) was associated with higher mortality across all age groups., Conclusion: Extended HD was not associated with lower mortality among octogenarians and nonagenarians, while it was associated with better survival among younger patients. Further studies are needed to determine the optimal treatment session length in elderly incident HD patients., (© 2018 S. Karger AG, Basel.)

Poor nutritional status and protein-energy wasting are common among maintenance dialysis patients and associated with unfavorable outcomes. Providing foods, meal trays, snack boxes, and/or oral nutritional supplements during hemodialysis can improve nutritional status and might also reduce inflammation, enhance health-related quality of life, boost patient satisfaction, and improve survival. Potential challenges include postprandial hypotension and other hemodynamic instabilities, aspiration risk, gastrointestinal symptoms, hygiene issues, staff burden, reduced solute removal, and increased costs. Differing in-center nutrition policies exist within organizations and countries around the world. Recent studies have demonstrated clinical benefits and highlight the need to work toward clear guidelines. Meals or supplements during hemodialysis may be an effective strategy to improve nutritional status with limited reports of complications in real-world scenarios. Whereas larger multicenter randomized trials are needed, meals and supplements during hemodialysis should be considered as a part of the standard-of-care practice for patients without contraindications., (Copyright © 2017. Published by Elsevier Inc.)