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Introduction: Niacin is a non-statin lipid-lowering therapy that has been shown to lower triglycerides and improve other risk factors for renal outcomes. Despite these favorable data, the effect of niacin on long-term kidney outcomes remains unclear. The aim of this study was to examine the associations of niacin therapies with incident chronic kidney disease (CKD), end-stage renal disease (ESRD), and death in patients with estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2., Methods: In a nationwide historic cohort of 1,139,630 United States (US) veterans with normal baseline eGFR, we examined the association of de novo prescription of niacin with incident CKD (defined as eGFR <60 mL/min/1.73 m2 on two occasions, separated by ≥90 days), ESRD (defined as the initiation of kidney replacement therapy), and death. Associations were examined in Cox proportional hazards models adjusted for demographics, major comorbidities, laboratory measurements, and medications. Prescription time-distribution matching was used to control for survival bias., Results: We identified 133,450 new users of niacin. Overall, patients (n = 1,139,630) had a mean (standard deviation) age of 60 (13) years, with 6% female, 78% white, 16% black, and 6% Hispanic. Niacin users were more likely to be male, white, current, or former smokers, with higher frequencies of comorbidities and statin use. Niacin use (vs. nonuse) was associated with a higher risk of CKD (HR: 1.08, 95% confidence interval:1.07-1.10) but a lower risk of ESRD (0.82, 0.76-0.88) and death (0.90, 0.89-0.91)., Conclusions: In a large national cohort of US veterans with normal kidney function, niacin use was associated with a lower risk of ESRD and death but with a higher risk of incident CKD, which is potentially explained by acute effects on eGFR. Further studies are needed to corroborate the potential benefits of niacin on kidney function and survival., (© 2025 S. Karger AG, Basel.)

Introduction: While Asian and Native Hawaiian and other Pacific Islander (NHOPI) patients have a high prevalence of kidney disease risk factors, there are sparse data examining their end-stage kidney disease (ESKD) outcomes. As Hawaii has high representation of Asian and NHOPI individuals, we compared their ESKD outcomes based on residence in the mainland USA versus Hawaii/Pacific Islands (PIs)., Materials and Methods: Using United States Renal Data System data, we examined the impact of geographic residence in the mainland versus Hawaii/PIs on race-mortality associations among incident ESKD patients transitioning to dialysis over January 1, 2000-December 31, 2016 using Cox regression. We examined likelihood of post-dialysis kidney transplantation using Cox models and cumulative incidence curves., Results: Compared with White patients in the mainland, Asian and NHOPI patients in the mainland had lower mortality: adjusted HRs (95% CIs) 0.67 (0.66-0.67) and 0.72 (0.70-0.73), respectively. When examining Asian and NHOPI patients in Hawaii/PIs, survival benefit was attenuated in Asian and diminished to the null in NHOPI patients (ref: mainland White patients). Cumulative incidence curves comparing Asian, NHOPI, and White patients showed Asian and NHOPI patients in the mainland had the highest likelihood of transplantation, whereas NHOPI and Asian patients in Hawaii/PIs had the lowest likelihood., Conclusion: In the mainland, Asian and NHOPI patients had lower mortality versus White patients, whereas in Hawaii/PIs, this survival benefit was diminished in Asian and mitigated in NHOPI patients. NHOPI and Asian patients in Hawaii/PIs had less transplantation versus those in the mainland. Further research is needed to uncover factors contributing to differential ESKD outcomes among Asian and NHOPI patients across geographic residence., (© 2023 S. Karger AG, Basel.)

Background: Several studies suggest that Asian-American and Native Hawaiian and Other Pacific Islander (NHOPI) racial/ethnic groups have a heightened risk of chronic kidney disease (CKD), but provide limited inference due to the aggregation of these groups into a single racial/ethnic category. We thus examined the association of granularly defined racial/ethnic groups with specific CKD indicators among a diverse group of participants from the National Kidney Foundation of Hawaii's Kidney Early Detection Screening (KEDS) Program., Methods: Among 1,243 participants enrolled in 19 KEDS screening events over 2006-2009, we examined the association between Asian-American and NHOPI groups and specific CKD indicators, defined as self-reported CKD, microalbuminuria, and macroalbuminuria, using multivariable logistic regression. We then examined associations of race/ethnicity with various CKD risk factors., Results: The most predominant racial/ethnic groups were White (22.0%), Multiracial (18.9%), Japanese (19.2%), Filipino (13.4%), NHOPI (8.4%), and Chinese (4.5%) participants. NHOPI and Chinese participants had a higher risk of microalbuminuria (adjusted ORs [aORs] [95% CIs] 2.48 [1.25-4.91] and 2.37 [1.07-5.27], respectively), while point estimates for all other minority groups suggested higher risk (reference: Whites). NHOPI participants also had a higher risk of macroalbuminuria and self-reported CKD. While most minorities had a higher risk of diabetes and hypertension, NHOPI and Multiracial participants had a higher risk of obesity, whereas the East Asian groups had a lower risk., Conclusions: In this community-based cohort, compared with Whites, Asian-Americans had a higher risk of early CKD indicators, whereas NHOPIs had a higher risk of more severe CKD indicators. Further studies are needed to elucidate the distinct pathways leading to CKD across diverse racial/ethnic groups in Hawaii., (© 2023 S. Karger AG, Basel.)

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.)

Introduction: Hypothyroidism is highly prevalent in end-stage kidney disease patients, and emerging data show that lower circulating thyroid hormone levels lead to downregulation of vascular calcification inhibitors and coronary artery calcification (CAC) in this population. To date, no studies have examined the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with CAC risk in hemodialysis patients., Methods: In secondary analyses of patients from the Anti-Inflammatory and Anti-Oxidative Nutrition in Hypoalbuminemic Dialysis Patients trial, we examined serum TSH levels and CAC risk assessed by cardiac computed tomography scans collected within a 90-day period. We evaluated the relationship between serum TSH with CAC Volume (VS) and Agatston score (AS) (defined as >100 mm3 and >100 Houndsfield Units, respectively) using multivariable logistic regression., Results: Among 104 patients who met eligibility criteria, higher TSH levels in the highest tertile were associated with moderately elevated CAC VS and AS in case-mix-adjusted analyses (ref: lowest tertile): adjusted ORs (95% CIs) 4.26 (1.18, 15.40) and 5.53 (1.44, 21.30), respectively. TSH levels >3.0 mIU/L (ref: ≤3.0 mIU/L) were also associated with moderately elevated CAC VS and AS. In secondary analyses, point estimates of incrementally lower direct free thyroxine levels trended toward elevated CAC VS and AS, although associations did not achieve statistical significance., Conclusions: In hemodialysis patients, higher serum TSH was associated with elevated CAC VS and AS. Further studies are needed to determine if thyroid hormone supplementation can attenuate CAC burden in this population., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Using a large diverse population of incident end-stage kidney disease (ESKD) patients from an integrated health system, we sought to evaluate the concordance of causes of death (CODs) between the underlying COD from the United States Renal Data System (USRDS) registry and CODs obtained from Kaiser Permanente Southern California (KPSC)., Methods: A retrospective cohort study was performed among incident ESKD patients who had mortality records and CODs reported in both KPSC and USRDS databases between January 1, 2007, and December 31, 2016. Underlying CODs reported by the KPSC were compared to the CODs reported by USRDS. Overall and subcategory-specific COD agreements were assessed using Cohen's weighted kappa statistic (95% CI). Proportions of positive and negative agreement were also determined., Results: Among 4,188 ESKD patient deaths, 4,118 patients had CODs recorded in both KPSC and USRDS. The most common KPSC CODs were circulatory system diseases (35.7%), endocrine/nutritional/metabolic diseases (24.2%), genitourinary diseases (12.9%), and neoplasms (9.6%). Most common USRDS CODs were cardiac disease (46.9%), withdrawal from dialysis (12.6%), and infection (10.1%). Of 2,593 records with causes listed NOT as "Other," 453 (17.4%) had no agreement in CODs between the USRDS and the underlying, secondary, tertiary, or quaternary causes recorded by KPSC. In comparing CODs recorded within KPSC to the USRDS, Cohen's weighted kappa (95% CI) was 0.20 (0.18-0.22) with overall agreement of 36.4%., Conclusion: Among an incident ESKD population with mortality records, we found that there was only fair or slight agreement between CODs reported between the USRDS registry and KPSC, a large integrated health care system., (© 2022 S. Karger AG, Basel.)

Background: Serum bicarbonate or total carbon dioxide (CO2) concentrations decline as chronic kidney disease (CKD) progresses and rise after dialysis initiation. While metabolic acidosis accelerates the progression of CKD and is associated with higher mortality among patients with end stage renal disease (ESRD), there are scarce data on the association of CO2 concentrations before ESRD transition with post-ESRD mortality., Methods: A historical cohort from the Transition of Care in CKD (TC-CKD) study includes 85,505 veterans who transitioned to ESRD from October 1, 2007, through March 31, 2014. After 1,958 patients without follow-up data, 3 patients with missing date of birth, and 50,889 patients without CO2 6 months prior to ESRD transition were excluded, the study population includes 32,655 patients. Associations between CO2 concentrations averaged over the last 6 months and its rate of decline during the 12 months prior to ESRD transition and post-ESRD all-cause, cardiovascular (CV), and non-CV mortality were examined by using hierarchical adjustment with Cox regression models., Results: The cohort was on average 68 ± 11 years old and included 29% Black veterans. Baseline concentrations of CO2 were 23 ± 4 mEq/L, and median (interquartile range) change in CO2 were -1.8 [-3.4, -0.2] mEq/L/year. High (≥28 mEq/L) and low (<18 mEq/L) CO2 concentrations showed higher adjusted mortality risk while there was no clear trend in the middle range. Consistent associations were observed irrespective of sodium bicarbonate use. There was also a U-shaped association between the change in CO2 and all-cause, CV, and non-CV mortality with the lowest risk approximately at -2.0 and 0.0 mEq/L/year among sodium bicarbonate nonusers and users, respectively, and the highest mortality was among patients with decline in CO2 >4 mEq/L/year., Conclusion: Both high and low pre-ESRD CO2 levels (≥28 and <18 mEq/L) during 6 months prior to dialysis transition and rate of CO2 decline >4 mEq/L/year during 1 year before dialysis initiation were associated with greater post-ESRD all-cause, CV, and non-CV mortality. Further studies are needed to determine the optimal management of CO2 in patients with advanced CKD stages transitioning to ESRD., (© 2021 S. Karger AG, Basel.)

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: 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.)

Background: It is not clear whether peritoneal dialysis (PD) and home hemodialysis (HHD) have similar outcomes, and little is known about how mortality associated with HHD versus PD differs according to the duration of dialysis., Methods: We examined a national cohort of incident end-stage renal disease patients that was comprised of 1,993 and 16,514 patients transitioning to HHD and PD, respectively, from 2007 to 2011. The HHD patients were matched with PD patients using propensity score (PS). Demographics, comorbidities, duration of dialysis, and body mass index were adjusted for in logistic regression models using PS matching. We matched 1,915 HHD patients with 1,915 PD patients based on the PS. The patients were categorized by their vintage (duration of dialysis) at the time of the transition to HHD or PD (<3, 3 to <12, and ≥12 months)., Results: In the matched cohort, 237 and 359 deaths occurred in the HHD and PD patients, respectively (cumulative incidence 9.6 vs. 12.9/100 patient-years, p < 0.001). PD patients who transitioned within 12 months of starting dialysis had similar mortality risks, while PD patients who transitioned >12 months after starting dialysis had an 83% higher risk for mortality (hazard ratio 1.83; 95% CI 1.33-2.52)., Conclusions: Whereas there was no meaningful survival difference in the first 12 months between HHD and PD, patients who transitioned to PD after 12 months of dialysis had worse survival than their HHD counterparts. Additional studies are warranted to investigate clinical implications of these differences., (© 2020 S. Karger AG, Basel.)

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease with an alarming case fatality rate up to 5%. The risk factors for severe presentations are concentrated in patients with chronic kidney disease, particularly patients with end-stage renal disease (ESRD) who are dialysis dependent. We report the first US case of a 56-year-old nondiabetic male with ESRD secondary to IgA nephropathy undergoing thrice-weekly maintenance hemodialysis for 3 years, who developed COVID-19 infection. He has hypertension controlled with angiotensin receptor blocker losartan 100 mg/day and coronary artery disease status-post stent placement. During the first 5 days of his febrile disease, he presented to an urgent care, 3 emergency rooms, 1 cardiology clinic, and 2 dialysis centers in California and Utah. During this interval, he reported nausea, vomiting, diarrhea, and low-grade fevers but was not suspected of COVID-19 infection until he developed respiratory symptoms and was admitted to the hospital. Imaging studies upon admission were consistent with bilateral interstitial pneumonia. He was placed in droplet-eye precautions while awaiting COVID-19 test results. Within the first 24 h, he deteriorated quickly and developed acute respiratory distress syndrome (ARDS), requiring intubation and increasing respiratory support. Losartan was withheld due to hypotension and septic shock. COVID-19 was reported positive on hospital day 3. He remained in critical condition being treated with hydroxychloroquine and tocilizumab in addition to the standard medical management for septic shock and ARDS. Our case is unique in its atypical initial presentation and highlights the importance of early testing., (© 2020 S. Karger AG, Basel.)

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: High ultrafiltration rate (UFR) has been associated with increased mortality in hemodialysis (HD) patients. However, the impact of UFR on decline of residual kidney function (RKF) has not been elucidated among patients receiving conventional HD., Methods: We performed a retrospective cohort study of 7,753 patients who initiated conventional HD from 2007 to 2011 and survived the first year of dialysis with baseline UFR and renal urea clearance (KRU) data at baseline and 1 year (5th patient-quarter). The primary exposure was average UFR at the 1st patient-quarter from dialysis initiation (<4, 4 to <6, 6 to <9, 9 to <13, and ≥13 mL/h/kg). Decline in RKF was defined as the percent change in KRU and decline in urine output during the first year after initiation of dialysis. We used a logistic regression model for rapid decline in RKF and a linear regression model for change in urine volume., Results: In our HD cohort, mean baseline UFR was 7.0 ± 3.1 mL/h/kg, and median (interquartile range) baseline KRU was 3.5 (2.1-5.3) mL/min/1.73 m2. There was a graded association between UFR and a rapid decline in RKF; the expanded case mix-adjusted ORs and 95% CIs were 1.21 (1.04-1.40), 1.34 (1.16-1.55), 1.73 (1.46-2.04), and 1.93 (1.48-2.52) for baseline UFR 4 to <6, 6 to <9, 9 to <13, and ≥13  mL/h/kg, respectively (reference: <4 mL/h/kg). KRU trajectories showed a greater KRU decline over time in higher UFR categories. Higher UFR was also associated with a greater decline in urine output after 1 year., Conclusion: Higher UFR was associated with a rapid decline in RKF among conventional HD patients. Further clinical trials are needed to elucidate a causal effect of UFR on RKF among HD patients., (© 2019 S. Karger AG, Basel.)

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.)

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.)

Background: Studies examining the association of dialysate potassium concentration and mortality in hemodialysis patients show conflicting findings. We hypothesized that low dialysate potassium concentrations are associated with higher mortality, particularly in patients with high pre-dialysis serum potassium concentrations., Methods: We evaluated 624 hemodialysis patients from the prospective Malnutrition, Diet, and Racial Disparities in Kidney Disease study recruited from 16 outpatient dialysis facilities over 2011-2015 who underwent protocolized collection of dialysis treatment characteristics every 6 months. We examined the association of dialysate potassium concentration, categorized as 1, 2, and 3 mEq/L, with all-cause mortality risk in the -overall cohort, and stratified by pre-dialysis serum potassium (< 5 vs. ≥5 mEq/L) using case-mix adjusted Cox models., Results: In baseline analyses, dialysate potassium concentrations of 1 mEq/L were associated with higher mortality, whereas concentrations of 3 mEq/L were associated with similar mortality in the overall cohort (reference: 2 mEq/L): adjusted hazard ratios (aHRs; 95% CI) 1.70 (1.01-2.88) and 0.95 (0.64-1.39), respectively. In analyses stratified by serum potassium, baseline dialysate potassium concentrations of 1 mEq/L were associated with higher mortality in patients with serum potassium ≥5 mEq/L but not in those with serum potassium < 5 mEq/L: aHRs (95% CI) 2.87 (1.51-5.46) and 0.74 (0.27-2.07), respectively (p interaction = 0.04). These findings were robust with incremental adjustment for serum potassium, potassium-binding resins, and potassium-modifying medications., Conclusion: Low (1 mEq/L) dialysate potassium -concentrations were associated with higher mortality, particularly in hemodialysis patients with high pre-dialysis serum potassium. Further studies are needed to identify therapeutic strategies that mitigate inter-dialytic serum potassium accumulation and subsequent high dialysate serum potassium gradients in this population., (© 2018 S. Karger AG, Basel.)

Background/aims: Cardiovascular disease and protein-energy wasting are among the strongest predictors of the high mortality of dialysis patients. In the general population, the novel cardiovascular and wasting biomarker, growth differentiation factor 15 (GDF15), is associated with decreased survival. However, little is known about GDF15 in dialysis patients., Methods: Among prevalent hemodialysis patients participating in a prospective study (October 2011 to August 2015), we examined the association of baseline GDF15 levels with all-cause mortality using unadjusted and case mix-adjusted death hazard ratios (HRs) that controlled for age, sex, race, ethnicity, diabetes, and dialysis vintage., Results: The mean age ± SD of the 203 patients included in the study was 53.2 ± 14.5 years, and the cohort included 41% females, 34% African-Americans, and 48% Hispanics. GDF15 levels (mean ± SD 5.94 ± 3.90 ng/mL; range 1.58-39.8 ng/mL) were higher among older patients and were inversely associated with serum creatinine concentrations as a surrogate for muscle mass. Each 1.0 ng/mL increase in GDF15 was associated with an approximately 17-18% higher mortality risk in the unadjusted and case mix models ( p < 0.05). Increments of about 1 SD (a 4.0 ng/mL increase in GDF15) were associated with a nearly 2-fold higher death risk. The highest GDF15 tertile was associated with higher mortality risk (reference: lowest tertile): the HRs (95% CI) were 3.19 (1.35-7.55) and 2.45 (1.00-6.00) in the unadjusted and the case mix-adjusted model, respectively. These incremental death trends were confirmed in cubic spline models., Conclusion: Higher circulating GDF15 levels are associated with higher mortality risk in hemodialysis patients. Future studies are needed to determine whether GDF15 may represent a novel therapeutic target for cardiovascular disease, wasting, and death in this population.

Background: The value of chronic kidney disease (CKD) screening in the general population remains unclear but may be beneficial in populations with high disease prevalence. We examined risk factors for albuminuria among participants in a state-wide CKD screening program in Hawaii., Methods: The National Kidney Foundation of Hawaii Kidney Early Detection Screening (NKFH-KEDS) program held 19 CKD screening events from 2006 to 2012. Participants rotated through 5 stations during which sociodemographic, blood glucose, urine albumin-to-creatinine ratio (ACR), and spot urine albumin data were collected. Multivariate logistic regression analyses (adjusted for age, sex, race/ethnicity, body mass index [BMI]) were used to identify clinical predictors of abnormal ACR (≥30 μg/mg) and abnormal spot urine albumin (>20 mg/L) levels., Results: Among 1,190 NKFH-KEDS participants who met eligibility criteria, 13 and 49% had abnormal ACR and urine albumin levels, respectively. In multivariate logistic regression analyses, participants of older age (>65 years), Asian and Pacific Islander race/ethnicity, BMI ≥30 kg/m2, and with hypertension had higher risk of abnormal ACR. Being of older age; Asian, Pacific Islander, and Mixed race/ethnicity; and having diabetes was associated with higher risk of abnormal urine albumin levels in adjusted analyses., Conclusions: NKFH-KEDS participants of older age; Asian and Pacific Islander race/ethnicity; and with obesity, hypertension, and diabetes had higher risk of kidney damage defined by elevated ACR and urine albumin levels. Further studies are needed to determine whether targeted screening programs can result in timely identification of CKD and implementation of interventions that reduce cardiovascular disease, death, and progression to end-stage renal disease., (© 2017 S. Karger AG, Basel.)

Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been previously suggested as oncologic prognostication markers. These are associated with malnutrition and inflammation, and hence, may provide benefit in predicting mortality among hemodialysis patients., Methods: Among 108,548 incident hemodialysis patients in a large U.S. dialysis organization (2007-2011), we compared the mortality predictability of NLR and PLR with baseline and time-varying covariate Cox models using the receiver operating characteristic curve (AUROC), net reclassification index (NRI), and adjusted R2., Results: During the median follow-up period of 1.4 years, 28,618 patients died. Median (IQR) NLR and PLR at baseline were 3.64 (2.68-5.00) and 179 (136-248) respectively. NLR was associated with higher mortality, which appeared stronger in the time-varying versus baseline model. PLR exhibited a J-shaped association with mortality in both models. NLR provided better mortality prediction in addition to demographics, comorbidities, and serum albumin; ΔAUROC and NRI for 1-year mortality (95% CI) were 0.010 (0.009-0.012) and 6.4% (5.5-7.3%) respectively. Additionally, adjusted R2 (95% CI) for the Cox model increased from 0.269 (0.262-0.276) to 0.283 (0.276-0.290) in the non-time-varying model and from 0.467 (0.461-0.472) to 0.505 (0.500-0.512) in the time-varying model. There was little to no benefit of adding PLR to predict mortality., Conclusions: High NLR in incident hemodialysis patients predicted mortality, especially in the short-term period. NLR, but not PLR, added modest benefit in predicting mortality along with demographics, comorbidities, and serum albumin, and should be included in prognostication approaches., (© 2017 S. Karger AG, Basel.)

Background: Higher serum ferritin levels may be influenced by iron use and inflammation, and are associated with higher mortality in hemodialysis (HD) patients. We hypothesized that a major rise in serum ferritin is associated with a higher risk of mortality, irrespective of baseline serum ferritin in incident HD patients., Methods: In a cohort of 93,979 incident HD patients between 2007 and 2011, we examined the association of change in serum ferritin from the baseline patient quarter (first 91 days from dialysis start) to the subsequent quarter with mortality. Multivariable adjustments were done for case-mix and markers of the malnutrition, and inflammation complex and intravenous iron dose. Change in serum ferritin was stratified into 5 groups: <-400, -400 to <-100, -100 to <100, 100 to <400, and ≥400 ng/mL/quarter., Results: The median change in serum ferritin was 89 ng/mL/quarter (interquartile range -55 to 266 ng/mL/quarter). Compared to stable serum ferritin (-100 to <100 ng/mL/quarter), a major rise (≥400 ng/mL/quarter) was associated with higher all-cause mortality (hazard ratio [95% CI] 1.07 [0.99-1.15], 1.17 [1.09-1.24], 1.26 [1.12-1.41], and 1.49 [1.27-1.76] according to baseline serum ferritin: <200, 200 to <500, 500 to <800, and ≥800 ng/mL in adjusted models, respectively. The mortality risk associated with a rise in serum ferritin was robust, irrespective of intravenous iron use., Conclusions: During the first 6-months after HD initiation, a major rise in serum ferritin in those with a baseline ferritin ≥200 ng/mL and even a slight rise in serum ferritin in those with a baseline ferritin ≥800 ng/mL are associated with higher mortality., (© 2017 S. Karger AG, Basel.)

Background: Among the general population, low circulating testosterone levels are associated with higher risk of cardiovascular disease and death. While testosterone deficiency is common in dialysis patients, studies of testosterone and mortality in this population are ambiguous and overlapping. We hypothesized that lower testosterone levels are associated with higher mortality in male dialysis patients., Methods: We examined a nationally representative cohort of male dialysis patients from a large US dialysis organization who underwent one or more total testosterone measurements from 1/2007 to 12/2011. The association between total testosterone categorized as quartiles and all-cause mortality was studied using Cox models adjusted for expanded case-mix and laboratory covariates. We also examined total testosterone as a continuous predictor of all-cause mortality using restricted cubic splines., Results: Among 624 male dialysis patients, 51% of patients demonstrated testosterone deficiency (total testosterone <300 ng/dL); median (IQR) total testosterone levels were 297 (190-424) ng/mL. In expanded case-mix + laboratory adjusted Cox analyses, we observed a graded association between lower testosterone levels and higher mortality risk (ref: quartile 3): adjusted hazard ratios (95% CI) 2.32 (1.33-4.06), 1.80 (0.99-3.28), and 0.68 (0.32-1.42) for Quartiles 1, 2, and 4, respectively. In adjusted spline analyses, the lower testosterone-higher mortality risk association declined with higher testosterone levels until the value reached a threshold of 400 ng/dL above which risk plateaued., Conclusion: Lower testosterone levels were independently associated with higher mortality risk in male dialysis patients. Further studies are needed to determine underlying mechanisms, and whether testosterone replacement ameliorates death risk in this population., (© 2017 S. Karger AG, Basel.)

Background: Hemoglobin variability (Hb-var) has been associated with increased mortality both in non-dialysis dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD) patients. However, the impact of Hb-var in advanced NDD-CKD on outcomes after dialysis initiation remains unknown., Methods: Among 11,872 US veterans with advanced NDD-CKD transitioning to dialysis between October 2007 through September 2011, we assessed Hb-var calculated from the residual SD of at least 3 Hb values during the last 6 months before dialysis initiation (prelude period) using within-subject linear regression models, and stratified into quartiles. Outcomes included post-transition all-cause, cardiovascular, and infection-related mortality, assessed in Cox proportional hazards models and adjusted for demographics, comorbidities, length of hospitalization, medications, estimated glomerular filtration rate (eGFR), type of vascular access, Hb parameters (baseline Hb [i.e., intercept] and change in Hb [i.e., slope]), and number of Hb measurements., Results: Higher prelude Hb-var was associated with use of iron and antiplatelet agents, tunneled dialysis catheter use, higher levels of baseline Hb, change in Hb, eGFR, and serum ferritin. After multivariable adjustment, higher prelude Hb-var was associated with higher post-ESRD all-cause and infection-related mortality, but not cardiovascular mortality (adjusted hazard ratios [95% CI] for the highest [vs. lowest] quartile of Hb-var, 1.10 [1.02-1.19], 1.28 [0.93-1.75], and 0.93 [0.79-1.10], respectively)., Conclusions: High pre-ESRD Hb-var is associated with higher mortality, particularly from infectious causes rather than cardiovascular causes. Further research is required to clarify the underlying mechanisms and true causal nature of the observed association., (© 2017 S. Karger AG, Basel.)

Like other biguanide agents, metformin is an anti-hyperglycemic agent with lower tendency towards hypoglycemia compared to other anti-diabetic drugs. Given its favorable effects on serum lipids, obese body habitus, cardiovascular disease, and mortality, metformin is recommended as the first-line pharmacologic agent for type 2 diabetes in the absence of contraindications. However, as metformin accumulation may lead to type B non-hypoxemic lactic acidosis, especially in the setting of kidney injury, chronic kidney disease, and overdose, regulatory agencies such as the United States Food and Drug Administration (FDA) have maintained certain restrictions regarding its use in kidney dysfunction. Case series have demonstrated a high fatality rate with metformin-associated lactic acidosis (MALA), and the real-life incidence of MALA may be underestimated by observational studies and clinical trials that have excluded patients with moderate-to-advanced kidney dysfunction. A recent study of advanced diabetic kidney disease patients in Taiwan in Lancet Endocrinology and Diabetes has provided unique insight into the potential consequences of unrestricted metformin use, including a 35% higher adjusted mortality risk that was dose-dependent. This timely study, as well as historical data documenting the toxicities of other biguanides, phenformin and buformin, suggest that the recent relaxation of FDA recommendations to expand metformin use in patients with kidney dysfunction (i.e., those with estimated glomerular filtration rates ≥30 instead of our recommended ≥45 ml/min/1.73 m2) may be too liberal. In this article, we will review the history of metformin use; its pharmacology, mechanism of action, and potential toxicities; and policy-level changes in its use over time., (© 2016 S. Karger AG, Basel.)

Background: Hyperkalemia is observed in chronic kidney disease patients and may be a risk factor for life-threatening arrhythmias and death. Race/ethnicity may be important modifiers of the potassium-mortality relationship in maintenance hemodialysis (MHD) patients given that potassium intake and excretion vary among minorities., Methods: We examined racial/ethnic differences in baseline serum potassium levels and all-cause and cardiovascular mortality using Cox proportional hazard models and restricted cubic splines in a cohort of 102,241 incident MHD patients. Serum potassium was categorized into 6 groups: ≤3.6, >3.6 to ≤4.0, >4.0 to ≤4.5 (reference), >4.5 to ≤5.0, >5.0 to ≤5.5, and >5.5 mEq/L. Models were adjusted for case-mix and malnutrition-inflammation cachexia syndrome (MICS) covariates., Results: The cohort was composed of 50% whites, 34% African-Americans, and 16% Hispanics. Hispanics tended to have the highest baseline serum potassium levels (mean ± SD: 4.58 ± 0.55 mEq/L). Patients in our cohort were followed for a median of 1.3 years (interquartile range 0.6-2.5). In our cohort, associations between higher potassium (>5.5 mEq/L) and higher mortality risk were observed in African-American and whites, but not Hispanic patients in models adjusted for case-mix and MICS covariates. While in Hispanics only, lower serum potassium (<3.6 mEq/L) levels were associated with higher mortality risk. Similar trends were observed for cardiovascular mortality., Conclusions: Higher potassium levels were associated with higher mortality risk in white and African-American MHD patients, whereas lower potassium levels were associated with higher death risk in Hispanics. Further studies are needed to determine the underlying mechanisms for the differential association between potassium and mortality across race/ethnicity., (© 2017 S. Karger AG, Basel.)

Background: Abnormalities in mineral and bone disorder (MBD) markers are common in patients with chronic kidney disease. However, previous studies have not accounted for their changes over time, and it is unclear whether these changes are associated with survival., Methods: We examined the association of change in MBD markers (serum phosphorus (Phos), albumin-corrected calcium (Ca(Alb)), intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP)) during the first 6 months of hemodialysis (HD) with all-cause mortality across baseline MBD strata using survival models adjusted for clinical characteristics and laboratory measurements in 102,754 incident HD patients treated in a large dialysis organization between 2007 and 2011., Results: Across all MBD markers (Phos, Ca(Alb), iPTH and ALP), among patients whose baseline MBD levels were higher than the reference range, increase in MBD levels was associated with higher mortality (reference group: MBD level within reference range at baseline and no change at 6 months follow-up). Conversely, decrease in Phos and iPTH, among baseline Phos and iPTH levels lower than the reference range, respectively, were associated with higher mortality. An increase in ALP was associated with higher mortality across baseline strata of ALP ≥80 U/l. However, patients with baseline ALP <80 U/l trended towards a lower risk of mortality irrespective of the direction of change at 6 months follow-up., Conclusions: There is a differential association between changes in MBD markers with mortality across varying baseline levels in HD patients. Further study is needed to determine if consideration of both baseline and longitudinal changes in the management of MBD derangements improves outcomes in this population., (© 2016 S. Karger AG, Basel.)

Background: Previous studies have not shown a consistent link between body mass index (BMI) and outcomes such as mortality and kidney disease progression in non-dialysis-dependent chronic kidney disease (CKD) patients. Therefore, we aimed to complete a systematic review and meta-analysis study on this subject., Methods: We searched MEDLINE, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Cochrane Central Register of Controlled Trials (CENTRAL), and screened 7,123 retrieved studies for inclusion. Two investigators independently selected the studies using predefined criteria and assessed each study's quality using the Newcastle-Ottawa quality assessment scale. We meta-analyzed the results based on the BMI classification system by the WHO., Results: We included 10 studies (with a total sample size of 484,906) in the systematic review and 4 studies in the meta-analyses. The study results were generally heterogeneous. However, following reanalysis of the largest reported study and our meta-analyses, we observed that in stage 3-5 CKD, being underweight was associated with a higher risk of death while being overweight or obese class I was associated with a lower risk of death; however, obesity classes II and III were not associated with risk of death. In addition, reanalysis of the largest available study showed that a higher BMI was associated with an incrementally higher risk of kidney disease progression; however, this association was attenuated in our pooled results. For earlier stages of CKD, we could not complete meta-analyses as the studies were sparse and had heterogeneous BMI classifications and/or referent BMI groups., Conclusion: Among the group of patients with stage 3-5 CKD, we found a differential association between obesity classes I-III and mortality compared to the general population, indicating an obesity paradox in the CKD population.

Background: Emerging data suggest that reduced exposure to ultraviolet (UV) radiation is associated with increased mortality in the general population. To date, the association between UV exposure and mortality in dialysis patients has not been examined., Methods: We examined the association between UV index, a proxy of UV exposure, and all-cause mortality among 47,286 US dialysis patients (entry period 2001-2006, with follow-up through 2009) from a large national dialysis organization using multivariable Cox regression. The UV index was ascertained by linking individual patients' residential zip codes to National Oceanic and Atmospheric Administration data, and was categorized as low (0-<3), moderate (3-<5), moderate-high (5-<6), high (6-<7), and very-high (≥7). In secondary analyses, we examined the UV index-mortality association within subgroups of age (<65 vs. ≥65 years old), sex, and race (white vs. non-white)., Results: The study population's mean ± SD age was 60 ± 16 and included 46% women and 56% diabetics. Compared to patients residing in moderate-high UV index regions, those residing in high and very-high UV index regions had a lower mortality risk: adjusted HRs 0.84 (95% CI) 0.81-0.88 and 0.83 (95% CI) 0.75-0.91, respectively. A similar inverse association between UV index and mortality was observed across all subgroups, although there was more pronounced reduction in mortality among whites vs. non-whites., Conclusion: These data suggest that dialysis patients residing in higher UV index regions have lower all-cause mortality compared to those living in moderate-high UV regions. Further studies are needed to determine the mechanisms underlying the UV index-mortality association., (© 2014 S. Karger AG, Basel.)

Background: A higher body mass index (BMI) seems to be linked to survival advantage in maintenance hemodialysis patients. However, it is uncertain if this 'obesity survival paradox' is also observed in kidney transplant recipients. Hence, we systematically reviewed the literature on the impact of pre-transplantation BMI on all-cause mortality in this population., Methods: We searched MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane CENTRAL for relevant studies up to July 2013. Two investigators independently selected the studies using predefined criteria, abstracted the data from the included studies, and independently assessed each study's quality using the Newcastle-Ottawa Quality Assessment Scale. In addition to the qualitative synthesis, we quantitatively pooled the results of the studies with clinical, methodological, and statistical homogeneity., Results: We screened 7,123 records, from which we included 11 studies (with a total of 305,392 participants) in this systematic review and 4 studies in the meta-analyses. In the only study that included children, obesity was linked to higher mortality in children of 6-12 years old. For adults, our meta-analyses indicated that compared to normal BMI, underweight [Hazard Ratio (HR): 1.09; 95% Confidence Interval (CI): 1.02-1.20], overweight (HR: 1.07; 95% CI: 1.04-1.12), and obese (HR: 1.20; 95% CI: 1.14-1.23) levels of BMI were associated with higher mortality., Conclusion: The presence of the obesity survival paradox is unlikely in kidney transplant recipients since both extremes of pre-transplantation BMI are linked to higher mortality in this population., (© 2014 S. Karger AG, Basel.)

Background: Observational studies have consistently demonstrated the survival benefits of a greater dialysis dose in maintenance hemodialysis (MHD) patients, whereas randomized controlled trials have shown conflicting results. The possible causal impact of dialysis dose on mortality needs to be investigated using rich cohort data analyzed with novel statistical methods such as marginal structural models (MSMs) that account for time-varying confounding and exposure., Methods: We quantified the effect of delivered dose of hemodialysis (HD) [single-pool Kt/V (spKt/V)] on mortality risk in a contemporary cohort of 68,110 patients undergoing HD 3 times weekly (7/2001- 9/2005). We compared conventional Cox proportional hazard and MSM survival analyses, accounting for time-varying confounding by applying longitudinally modeled inverse-probability-of-dialysis-dose weights to each observation., Results: In conventional Cox models, baseline spKt/V showed a weak negative association with mortality, while higher time-averaged spKt/V was strongly associated with lower mortality risk. In MSM analyses, compared to a spKt/V range of 1.2 - <1.4, a spKt/V range of <1.2 was associated with a higher risk of mortality [HR (95% CI) 1.67 (1.54 - 1.80)], whereas mortality risks were significantly lower with higher spKt/V [HRs (95% CI): 0.74 (0.70-0.78), 0.63 (0.59-0.66), 0.56 (0.52-0.60), and 0.56 (0.52-0.61) for spKt/V ranges of 1.4 - <1.6, 1.6-<1.8, 1.8 - <2.0, and ≥2.0, respectively]. Thus, MSM analyses showed that the greatest survival advantage of a higher dialysis dose was observed for a spKt/V range of 1.8-<2.0, and the dialysis dose-mortality relationship was robust in almost all subgroups of patients., Conclusions: Higher HD doses were robustly associated with greater survival in MSM analyses that more fully and appropriately accounted for time-varying confounding.

Background: Prior studies show that African-American and Hispanic dialysis patients have lower mortality risk than whites. Recent age-stratified analyses suggest this survival advantage may be limited to younger age groups, but did not concurrently compare Hispanic, African-American, and white patients, nor account for differences in nutritional and inflammatory status as potential confounders. Minorities experience inequities in kidney transplantation access, but it is unknown whether these racial/ethnic disparities differ across age groups., Methods: The associations between race/ethnicity with all-cause mortality and kidney transplantation were separately examined among 130,909 adult dialysis patients from a large national dialysis organization (entry period 2001-2006, follow-up through 2009) within 7 age categories using Cox proportional hazard models adjusted for case-mix and malnutrition and inflammatory surrogates., Results: African-Americans had similar mortality versus whites in younger age groups (18-40 years), but decreased mortality in older age groups (>40 years). In contrast, Hispanics had lower mortality versus whites across all ages. In sensitivity analyses using competing risk regression to account for differential kidney transplantation rates across racial/ethnic groups, the African-American survival advantage was limited to >60-years age categories. African-Americans and Hispanics were less likely to undergo kidney transplantation from all donor types versus whites across all ages, and these disparities were even more pronounced for living donor kidney transplantation (LDKT)., Conclusions: Hispanic dialysis patients have greater survival versus whites across all ages; in African-Americans, this survival advantage is limited to patients >40 years of age. Minorities are less likely to undergo kidney transplantation, particularly LDKT, across all ages.

Background: Although hemoglobin A1c (HbA1c) has been widely used as a clinical assessment tool for outcome analyses related to glycemic control, the relationship between HbA1c and average blood glucose (BG) specific to peritoneal dialysis (PD) patients with diabetes has not been characterized. We sought to develop HbA1c-BG equation models for PD patients., Methods: We examined associations between HbA1c and random serum BG values over time in a contemporary 5-year (2001-2006) cohort of DaVita PD patients with diabetes. We identified 850 patients (mean age: 58 ± 13 years, 56% male) with 4,566 paired measurements of HbA1c and BG. The bootstrapping method was used to estimate average BG and corresponding HbA1c., Results: Linear regression analyses yielded the following HbA1c-BG equations: (1) BG (mg/dl) = 24.1 + 28.6 × HbA1c - 12.2 × albumin [adjusted R(2) (R(2)adj = 0.454)], (2) BG = 55.3 + 28.8 × HbA1c - 10.2 × albumin - 3.3 × Hb (R(2)adj = 0.457), and (3) BG = 69.5 + 28.7 × HbA1c - 10.1 × albumin - 3.7 × Hb - 0.1 × age + race/ethnicity (-10.1 African Americans, -5.4 other race/ethnicities; R(2)adj = 0.457). All models showed greater explanatory power of BG variation than previously established HbA1c-BG equation models defined within non-PD cohorts [R(2)adj = 0.446 for both the Diabetes Control and Complications Trial (DCCT) and the A1c-Derived Average Glucose (ADAG) equations]., Conclusions: The association between HbA1c and BG in PD patients is different than that of patients with normal kidney function. Our analysis suggests that equations incorporating serum albumin and/or Hb values better estimate the HbA1c-BG relationship in PD patients compared to equations using HbA1c alone., (Copyright © 2013 S. Karger AG, Basel.)