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Introduction: Information on whether race and ethnicity are associated with a greater risk of recurrent hyperkalemia is limited. The aim of this study was to examine the association between race or ethnicity and recurrent hyperkalemia in a population of US veterans., Methods: This retrospective study used the US Veterans Affairs database to identify adults (aged ≥18 years) with at least one serum potassium measurement during the study period who ever experienced hyperkalemia (serum potassium > 5.0 mmol/L). The proportion of patients with hyperkalemia recurrence (≥1 subsequent event) within one year was determined for different race and ethnicity groups. The association between patient race and ethnicity and the risk of hyperkalemia recurrence within one year after the index hyperkalemia event was analyzed using competing risk regression., Results: Among a total of 1,493,539 veterans with incident hyperkalemia (median age (interquartile range): 61.0 years (54.0, 71.0)), recurrence within one year occurred in 19.1% of Black, 16.0% of Native Hawaiian/other Pacific Islander, 15.1% of White, 14.9% of American Indian/Alaska Native, and 13.1% of Asian patient groups. Recurrent hyperkalemia occurred in 18.1% of Hispanic and 15.6% of non-Hispanic patient groups. In a fully-adjusted regression model, recurrent hyperkalemia risk was significantly higher in Black versus White patient groups (subhazard ratio (sHR), 1.17; 95% confidence interval (CI), 1.16-1.19; p< 0.0001) and in Hispanic versus non-Hispanic patient groups (sHR, 1.30; 95% CI, 1.28-1.33; p< 0.0001)., Discussion/conclusion: Among US veterans with incident hyperkalemia, the risk of recurrent hyperkalemia was higher in Black and Hispanic patient groups. This information may be useful for health system screenings to risk stratify patient groups and both guide the frequency of serum potassium monitoring and better understand the root causes of group differences., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Ahdoot et al.)

Purpose: Workforce shortages will impact oncologists' ability to provide both active and survivorship care. While primary care provider (PCP) or survivorship clinic transition has been emphasized, there is little evidence regarding patient comfort., Methods: We developed an online survey in partnership with patient advocates to assess survivors' comfort with PCP or survivorship clinic care and distributed the survey to online, cancer-specific patient communities from June to August 2020. Descriptive and logistic regression analyses were conducted., Results: A total of 975 surveys were complete. Most respondents were women (91%) and had private insurance (65%). Thirty-six cancer types were reported. Ninety-three percent had a PCP. Twenty-four percent were comfortable seeing a PCP for survivorship care. Higher odds of comfort were seen among respondents who were Black or had stage 0 cancer; female sex was associated with lower odds. Fifty-five percent were comfortable with a survivorship clinic. Higher odds of comfort were seen with lymphoma or ovarian cancer, > 15 years from diagnosis, and non-US government insurance. Lower odds were seen with melanoma, advanced stage, Medicaid insurance, and one late effect. Preference for PCP care was 87% for general health, 32% for recurrence monitoring, and 37% for late effect management., Conclusions: One quarter of cancer survivors were comfortable with PCP-led survivorship care and about half with a survivorship clinic. Most preferred oncologist care for recurrence monitoring and late-effect management., Implications for Cancer Survivors: Patient preference and comfort should be considered when developing survivorship care models. Future efforts should focus on facilitating patient-centered transitions to non-oncologist care., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Liver disease is often associated with dysfunctional potassium homeostasis but is not a well-established risk factor for hyperkalemia. This retrospective cohort study examined the potential relationship between liver disease and recurrent hyperkalemia. Patients with ≥1 serum potassium measurement between January 2004 and December 2018 who experienced hyperkalemia (serum potassium >5.0 mmol/L) were identified from the United States Veterans Affairs database. A competing risk regression model was used to analyze the relationship between patient characteristics and recurrent hyperkalemia. Of 1,493,539 patients with incident hyperkalemia, 71,790 (4.8%) had liver disease (one inpatient or two outpatient records) within 1 year before the index hyperkalemia event. Recurrent hyperkalemia within 1 year after the index event occurred in 234,807 patients (15.7%) overall, 19,518 (27.2%) with liver disease, and 215,289 (15.1%) without liver disease. The risk of recurrent hyperkalemia was significantly increased in patients with liver disease versus those without (subhazard ratio, 1.34; 95% confidence interval, 1.32-1.37; p < 0.0001). Aside from vasodilator therapy, the risk of recurrent hyperkalemia was not increased with concomitant medication. In this cohort study, liver disease was an independent risk factor strongly associated with recurrent hyperkalemia within 1 year, independent of concomitant renin-angiotensin-aldosterone system inhibitor or potassium-sparing diuretic use.

Introduction: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Previous studies have shown that the relationship of triglycerides (TGs) with outcomes changes across stages of CKD. Our objective was to examine the association of TG independent of other metabolic syndrome components with renal outcomes in diabetic patients with or without CKD., Methods: This retrospective cohort study included diabetic US veteran patients with valid data on TGs, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin/creatinine ratio) between fiscal years 2004 and 2006. Using Cox models adjusted for clinical characteristics and laboratory markers, we evaluated the relationship of TG with incident albuminuria (stratified by eGFR category) and based on eGFR (stratified by baseline albuminuria categories). To evaluate the relationship of TG with time to end-stage renal disease (ESRD), we stratified models by baseline CKD stage (eGFR category) and baseline albuminuria stage ascertained at time of TG measurement., Results: In a cohort of 138,675 diabetic veterans, the mean ± SD age was 65 ± 11 years old and included 3% females and 14% African Americans. The cohort also included 28% of patients with non-dialysis-dependent CKD (eGFR &lt;60 mL/min/1.73 m2), as well as 28% of patients with albuminuria (≥30 mg/g). The median (IQR) of serum TG was 148 (100, 222) mg/dL. We observed a slight positive linear association between TG and incident CKD after adjustment for Case-Mix and Laboratory variables among non-albuminuric and microalbuminuric patients. The relationship of high TG trended towards a higher risk of ESRD in CKD 3A non-albuminuric patients and in CKD 3A and 4/5 patients with microalbuminuria., Conclusion: In a large cohort, we have shown that elevated TGs are associated with all kidney outcomes tested independently of other metabolic syndrome components in diabetic patients with normal eGFR and normal albumin excretion rate, but the association is weaker in some groups of diabetic patients with preexisting renal complications., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Hyperkalemia is associated with kidney function decline in patients with non-dialysis dependent chronic kidney disease, but this relationship is unclear for residual kidney function (RKF) among hemodialysis (HD) patients., Methods: We conducted a retrospective cohort study of 6655 patients, who started HD January 2007 and December 2011 and who had data on renal urea clearance (KRU). Serum potassium levels were stratified into four groups (i.e. ≤4.0, &gt;4.0 to ≤4.5, &gt;4.5 to ≤5.0 and &gt;5.0 mEq/L) and 1-year KRU slope for each group was estimated by a linear mixed-effects model., Results: Higher serum potassium was associated with a greater decline in KRU, and the greatest decrease in KRU (-0.20, 95% confidence interval -0.50 to -0.06) was observed for baseline potassium &gt;5.0 mEq/L in the fully adjusted model. Mediation analysis showed that KRU slope mediated 1.78% of the association between serum potassium and mortality., Conclusions: Hyperkalemia is associated with a decline in RKF amongst incident HD patients. These findings may have important clinical implications in the management of hyperkalemia in advanced CKD if confirmed in additional clinical trials., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Serum globulin is a major component of total protein and can be elevated in inflammatory disease states. While inflammation is common in hemodialysis patients and associated with mortality and morbidity, the association between serum globulin and mortality has never been examined in hemodialysis patients., Methods: In a retrospective cohort of 104 164 incident hemodialysis patients treated by a large dialysis organization from 2007 to 2011, we explored the association between baseline serum globulin, albumin: globulin (A:G) ratio and serum protein levels and all-cause, cardiovascular and infection-related mortality with adjustments for demographic variables and laboratory markers of malnutrition and inflammation using Cox proportional hazards models., Results: Patients with a globulin concentration >3.8 g/dL had a higher all-cause and infection-related mortality risk {hazard ratio [HR] 1.11 [95% confidence interval (CI) 1.06-1.16] and HR 1.28 [95% CI 1.09-1.51], respectively} in the fully adjusted model when compared with the reference group of 3.0- <3.2 g/dL. In addition, patients with an A:G ratio <0.75 had a 45% higher all-cause mortality hazard [HR 1.45 (95% CI 1.38-1.52)] and patients with total serum protein <5.5 g/dL had a 34% higher risk of death [1.34 (95% CI 1.27-1.42)] when compared with the reference (A:G ratio 1.05- <1.15 and total serum protein 6.5- <7 g/dL)., Conclusions: Among incident hemodialysis patients, a higher globulin level was associated with a higher mortality risk independent of other markers of malnutrition and inflammation, including albumin. A lower A:G ratio and serum protein was also associated with a higher mortality hazard. The mechanisms that contribute to elevated serum globulin should be further explored., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Objective: In advanced chronic kidney disease (CKD), patients with obesity often have better outcomes than patients without obesity, often called the 'obesity paradox'. Yet, in CKD, the prevalence of inflammation increases as CKD progresses. Although a potential confounder, inflammation may be left unaccounted in obesity-mortality studies. We examined the associations of body mass index (BMI) with all-cause and cause-specific mortality across CKD stages, with consideration for uncontrolled confounding due to unmeasured inflammation., Methods: We investigated 2,703,512 patients with BMI data between 2004 and 2006. We used Cox models to examine the associations of BMI with all-cause, cardiovascular, and cancer mortality, (ref: BMI 25-<30 kg/m 2 ), adjusted for clinical characteristics and stratified by CKD stages. To address uncontrolled confounding, we performed bias analysis using a weighted probabilistic model of inflammation given the observed data applied to weighted Cox models., Results: The cohort included 5% females and 14% African Americans. In adjusted analyses, the associations of the BMI with all-cause and cardiovascular mortality showed a reverse J-shape, where a higher BMI (>40 kg/m 2 ) was associated with a higher risk. Conversely, a lower mortality risk was observed with a BMI 30-<35 kg/m 2 across all CKD stages and for BMI >40 kg/m 2 in CKD stage 4/5. Cancer mortality analyses showed an inverse relationship. Bias analysis for uncontrolled confounding suggested that independent of inflammation, the obesity paradox was present., Conclusion: We observed the presence of the obesity paradox in this study. This association was consistent in advanced CKD and in our bias analysis, suggesting that inflammation may not fully explain the observed BMI-mortality associations including in patients with CKD., (Copyright © 2021 National Kidney Foundation, Inc. All rights reserved.)

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

Background: Hyponatremia is one of the most common electrolyte disturbances in advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD) patients, and has been shown to be associated with higher mortality risk. However, the relationship between hyponatremia during late-stage CKD and the risk of poor outcomes after ESKD transition is unknown., Methods: We conducted a retrospective cohort study including 32 257 US veterans transitioning to ESKD from 1 October 2007 to 30 March 2015. We evaluated adjusted associations between the 3-month averaged pre-transition to ESKD serum sodium and all-cause mortality. Secondary outcomes included cardiovascular (CV) mortality, infection-related mortalities and hospitalization rate., Results: Cohort mean ± standard deviation serum sodium was 139 ± 3 mEq/L, mean age was 67 ± 11 years, 98% were male and 28% were African American. Over a median (interquartile range) follow-up of 702 days (296, 1301) there were 17 162 deaths. Compared with the reference of 135 to <144 mEq/L, the lowest serum sodium group (<130 mEq/L) had a 54% higher all-cause mortality risk [hazard ratio 1.54 (95% confidence interval 1.34-1.76)] in the fully adjusted model. Associations were similar for CV and infection-related mortality, and hospitalization outcomes., Conclusions: Hyponatremia prior to ESKD transition is associated with higher risk of all-cause, CV and infection-related mortalities, and hospitalization rates after ESKD transition. Future studies evaluating management of pre-ESKD hyponatremia may be indicated to improve patient outcomes for those transitioning to ESKD., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Background: Previous studies have suggested that metabolic syndrome (MetS) components are associated with renal outcomes, defined as a decline in kidney function or reaching end-stage renal disease (ESRD). Elevated triglycerides (TGs) are a component of MetS that have been reported to be associated with renal outcomes. However, the association of TGs with renal outcomes in chronic kidney disease (CKD) patients independent of the other components of the MetS remains understudied., Methods: We examined 1,657,387 patients with data on TGs and other components of MetS in 2004-2006 and followed up until 2014. Patients with ESRD on renal replacement therapy were excluded. We examined time to ESRD, estimated glomerular filtration rate (eGFR) slope (renal function decline), and time to incident CKD (eGFR <60 mL/min/1.73 m2) among baseline normal kidney function (non-CKD) patients, using Cox or logistic regression, adjusted for clinical characteristics and MetS components. We also stratified analyses by the number of MetS components., Results: The cohort was on average 64 years old and comprised 5% females, 15% African Americans, and 24% with nondialysis-dependent CKD. Among non-CKD patients, the adjusted relationship of TGs with time to incident CKD was strong and linear. Compared to TGs 120-<160 mg/dL, higher TGs were associated with a faster renal function decline across all CKD stages. Elevated TGs ≥240 mg/dL were associated with a faster time to ESRD among non-CKD and CKD stages 3A-3B, while the risk gradually declined to null or lower in CKD stages 4-5. Models were robust after MetS component adjustment and stratification., Conclusion: Independent of MetS components, high TGs levels were associated with a higher incidence of CKD and a faster renal function decline, yet showed no or inverse associations with time to ESRD in CKD stages 4-5. Examining the effects of TGs-lowering interventions on incident CKD and kidney preserving therapy warrants further studies including clinical trials., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

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

Background: Transitioning to maintenance hemodialysis (HD) is a vulnerable period for persons with end-stage renal disease (ESRD), punctuated by high rates of depression, hospitalizations and death. Screening for depression during this time may help to improve patient outcomes but formal inquiry has yet to be conducted. Among a national Veteran cohort, we examined whether depression screening in the year prior to HD initiation led to improved outcomes in the year thereafter., Methods: Associations between pre-ESRD depression screening and post-ESRD outcomes were examined with Cox proportional hazards models (mortality) and Poisson regression models (hospitalization). Hierarchal adjustment models accounted for sociodemographic, clinical, pre-ESRD care and dialysis characteristics., Results: The final analytic cohort of the study was 30 013 Veterans of whom 64% underwent pre-ESRD depression screening. During the 12 months post-transition, the crude all-cause mortality rate was 0.32 person-year for those screened and 0.35 person-year for those not screened, while the median (interquartile range) hospitalizations were 2 (2, 2) per year for both groups. In fully adjusted models, pre-ESRD depression screening was associated with a lower risk of mortality [hazard ratio (95% confidence interval): 0.94 (0.90-0.99)] and hospitalization [incidence rate ratio (95% confidence interval): 0.97 (0.9-0.99)]., Conclusion: Depression screening among adults prior to maintenance HD transition may be associated with better outcomes during the following year., (Published by Oxford University Press on behalf of ERA-EDTA 2021.)

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: While direct oral anticoagulants (DOACs) are considered safe among patients without chronic kidney disease (CKD), the evidence is conflicting as to whether they are also safe in the CKD and end-stage kidney disease (ESKD) population. In this observational cohort study, we examined whether DOACs are a safe alternative to warfarin across CKD stages for a variety of anticoagulation indications., Methods: Individuals on DOACs or warfarin were identified from OptumLabs® Data Warehouse (OLDW), a longitudinal dataset with de-identified administrative claims, from 2010 to 2017. Cox models with sensitivity analyses were used to assess the risk of cardiovascular disease and bleeding outcomes stratified by CKD stage., Results: Among 351,407 patients on anticoagulation, 45% were on DOACs. CKD stages 3-5 and ESKD patients comprised approximately 12% of the cohort. The most common indications for anticoagulation were atrial fibrillation (AF, 44%) and venous thromboembolism (VTE, 23%). DOACs were associated with a 22% decrease in the risk of cardiovascular outcomes (HR 0.78, 95% CI: 0.77-0.80, p < 0.001) and a 10% decrease in the risk of bleeding outcomes (HR 0.90, 95% CI: 0.88-0.92, p < 0.001) compared to warfarin after adjustment. On stratified analyses, DOACs maintained a superior safety profile across CKD stages. Patients with AF on DOACs had a consistently lower risk of cardiovascular and bleeding events than warfarin-treated patients, while among other indications (VTE, peripheral vascular disease, and arterial embolism), the risk of cardiovascular and bleeding events was the same among DOAC and warfarin users., Conclusion: DOACs may be a safer alternative to warfarin even among CKD and ESKD patients., (© 2021 The Author(s) Published by 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: 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.)

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: 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.)

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.)

Background: Vitamin D deficiency is common among dialysis patients and may impact blood concentrations of calcium, phosphorus, intact parathyroid hormone (iPTH), and alkaline phosphatase (ALP). Seasonal variation of serum 25-hydroxyvitamin D [25(OH)D] concentrations has been well established for the general population; however, less is known about circannual variation in 25(OH)D as well as other parameters of mineral and bone disorder among dialysis patients., Method: Based on 57,500 serum 25(OH)D measurements collected over two years from January 2009 to December 2010 among 25,025 dialysis patients, we evaluated the circannual variations in serum concentrations of 25(OH)D, calcium, phosphorus, iPTH, and ALP by a linear regression model with a cosinor function for the time period (month). We adjusted for potential confounders including case-mix variables, and ultraviolet index., Results: Serum 25(OH)D concentrations showed significant circannual variation and mean serum 25(OH)D was 3.2 ng/mL higher in summer than in winter. Furthermore, 25(OH)D concentration increased steadily by 1.3 ng/mL per year. While serum calcium concentrations showed statistically significant but clinically negligible seasonal variation (0.02 mg/dL in peak-trough difference), serum phosphorus did not follow such a pattern. Serum iPTH concentrations also showed a modest seasonal variation with 9% higher values in winter than in summer. Concordantly, ALP concentrations in the winter were 2% higher than in the summer time. Seasonal variation of 25(OH)D was greater in male (vs. female), African-American (vs. non-African-American), and younger (vs. older) dialysis patients., Conclusion: Serum 25(OH)D and iPTH concentrations show seasonal variation among dialysis patients while the variation in other parameters of mineral and bone disorder was clinically irrelevant, if any. Serum 25(OH)D also showed a gradual increase over time. Clinicians and researchers should be aware of these changes when interpreting laboratory results in dialysis patients., (Copyright © 2019. Published by Elsevier Inc.)

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.)

Precision medicine is an emerging field that calls for individualization of treatment strategies based on characteristics unique to each patient. In lipid management, current guidelines are driven mainly by clinical trial results that presently indicate that patients with non-dialysis-dependent chronic kidney disease (CKD) should be treated with a β-hydroxy β-methylglutaryl-CoA reductase inhibitor, also known as statin therapy. For patients with end-stage kidney disease (ESKD) being treated with hemodialysis, statin therapy has not been shown to successfully reduce poor outcomes in trials and therefore is not recommended. The two major guidelines dissent on whether statin therapy should be of moderate or high intensity in non-dialysis-dependent CKD patients, but often leave the prescribing clinician to make that decision. These decisions often are complicated by the increased concerns for adverse events such as myopathies in patients with advanced kidney disease and ESKD. In the future, there may be an opportunity to further identify CKD and ESKD patients who are more likely to benefit from lipid-modifying therapy as opposed to those who likely will suffer from its side effects using precision medicine tools. For now, data from genetics studies and subgroup analyses may provide insight for future research directions in this field and we review some of the work that has been published in this regard., (Copyright © 2018 Elsevier Inc. All rights reserved.)

While obesity is associated with a variety of complications including diabetes, hypertension, cardiovascular disease and premature death, observational studies have also found that obesity and increasing body mass index (BMI) can be linked with improved survival in certain patient populations, including those with conditions marked by protein-energy wasting and dysmetabolism that ultimately lead to cachexia. The latter observations have been reported in various clinical settings including end-stage renal disease (ESRD) and have been described as the "obesity paradox" or "reverse epidemiology", engendering controversy. While some have attributed the obesity paradox to residual confounding in an effort to "debunk" these observations, recent experimental discoveries provide biologically plausible mechanisms in which higher BMI can be linked to longevity in certain groups of patients. In addition, sophisticated epidemiologic methods that extensively adjusted for confounding have found that the obesity paradox remains robust in ESRD. Furthermore, novel hypotheses suggest that weight loss and cachexia can be linked to adverse outcomes including cardiomyopathy, arrhythmias, sudden death and poor outcomes. Therefore, the survival benefit observed in obese ESRD patients can at least partly be derived from mechanisms that protect against inefficient energy utilization, cachexia and protein-energy wasting. Given that in ESRD patients, treatment of traditional risk factors has failed to alter outcomes, detailed translational studies of the obesity paradox may help identify innovative pathways that can be targeted to improve survival. We have reviewed recent clinical evidence detailing the association of BMI with outcomes in patients with chronic kidney disease, including ESRD, and discuss potential mechanisms underlying the obesity paradox with potential for clinical applicability., (Copyright © 2018 Elsevier Inc. All rights reserved.)