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Study objectivesPatients with end-stage kidney disease commonly experience sleep disturbances. Sleep disturbance has been inconsistently associated with mortality risk in patients on hemodialysis, but the burden of symptoms from sleep disturbances has emerged as a marker that may shed light on these discrepancies and guide treatment decisions. This study examines whether functional outcomes of sleep are associated with increased risk of intermediary cardiovascular outcomes or mortality among adults initiating hemodialysis.MethodsIn 228 participants enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease study, the Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), which assesses functional outcomes of daytime sleepiness, was administered within 6 months of enrollment. Intermediary cardiovascular outcomes included QT correction (ms), heart rate variance (ms2), left ventricular mass index (g/m2), and left ventricular hypertrophy. The association of FOSQ-10 score with all-cause mortality was examined using proportional hazards regression.ResultsMean age was 55 years, and median body mass index was 28 kg/m2 (interquartile range, 24, 33), with 70% of patients being African Americans. Median FOSQ-10 score was 19.7 (interquartile range, 17.1, 20.0). A 10% lower FOSQ-10 score was associated with increased mortality risk (hazard ratio, 1.09; 95% confidence interval, 1.01-1.18). Lower FOSQ-10 scores were associated with longer QT correction duration and lower heart rate variance but not left ventricular mass index or left ventricular mass index.ConclusionsIn adults initiating dialysis, sleep-related functional impairment is common and is associated with intermediary cardiovascular disease measures and increased mortality risk. Future studies should assess the impact of screening for sleep disturbances in patients with end-stage kidney disease to identify individuals at increased risk for cardiovascular complications and death.CitationFitzpatrick J, Kerns ES, Kim ED, et al. Functional outcomes of sleep predict cardiovascular intermediary outcomes and all-cause mortality in patients on incident hemodialysis. J Clin Sleep Med. 2021;17(8):1707-1715.

BackgroundA better understanding of the pathophysiology involving coronary artery calcification (CAC) in patients on hemodialysis (HD) will help to develop new therapies. We sought to identify the differences in metabolomics profiles between patients on HD with and without CAC.MethodsIn this case-control study, nested within a cohort of 568 incident patients on HD, the cases were patients without diabetes with a CAC score >100 (n=51), and controls were patients without diabetes with a CAC score of zero (n=48). We measured 452 serum metabolites in each participant. Metabolites and pathway scores were compared using Mann-Whitney U tests, partial least squares-discriminant analyses, and pathway enrichment analyses.ResultsCompared with controls, cases were older (64±13 versus 42±12 years) and were less likely to be Black (51% versus 94%). We identified three metabolites in bile-acid synthesis (chenodeoxycholic, deoxycholic, and glycolithocholic acids) and one pathway (arginine/proline metabolism). After adjusting for demographics, higher levels of chenodeoxycholic, deoxycholic, and glycolithocholic acids were associated with higher odds of having CAC; comparing the third with the first tertile of each bile acid, the OR was 6.34 (95% CI, 1.12 to 36.06), 6.73 (95% CI, 1.20 to 37.82), and 8.53 (95% CI, 1.50 to 48.49), respectively. These associations were no longer significant after further adjustment for coronary artery disease and medication use. Per 1 unit higher in the first principal component score, arginine/proline metabolism was associated with CAC after adjusting for demographics (OR, 1.83; 95% CI, 1.06 to 3.15), and the association remained significant with additional adjustments for statin use (OR, 1.84; 95% CI, 1.04 to 3.27).ConclusionsAmong patients on HD without diabetes mellitus, chenodeoxycholic, deoxycholic, and glycolithocholic acids may be potential biomarkers for CAC, and arginine/proline metabolism is a plausible mechanism to study for CAC. These findings need to be confirmed in future studies.

BackgroundJohns Hopkins was an early adopter of an in-house nephrology fellowship night float to improve work-life balance. Our study aimed to elucidate attitudes to guide fellowship structuring.MethodsWe performed a mixed-methods study surveying Johns Hopkins fellows, alumni, and faculty and conducting one focus group of current fellows. Surveys were developed through literature review, queried on a five-point Likert scale, and analyzed with t and ANOVA tests. The focus group transcript was analyzed by two independent reviewers.ResultsSurvey response rates were 14 (100%) fellows, 32 (91%) alumni, and 17 (94%) faculty. All groups felt quality of patient care was good to excellent with no significant differences among groups (range of means [SD], 4.1 [0.7]-4.6 [0.7]; P=0.12), although fellows had a statistically significantly more positive view than faculty on autonomy (4.6 [0.5] versus 4.1 [0.3]; P=0.006). Fellows perceived a positive effect across all domains of night float on the day team experience (range, 4.2 [0.8]-4.6 [0.6]; P

IntroductionMagnesium (Mg) may protect against arterial calcification. We tested the hypotheses that a higher serum Mg concentration is associated with less arterial calcification and stiffness in patients on hemodialysis (HD) and that these associations are modified by diabetes mellitus.MethodsWe performed cross-sectional analyses of 367 incident HD patients from the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) cohort. Measures of arterial calcification and stiffness included coronary arterial calcification (CAC) and thoracic aortic calcification (TAC) scores, ankle brachial index (ABI; high ABI: >1.4 or incompressible vessels), pulse wave velocity (PWV), and pulse pressure.ResultsMean Mg was 1.8 ± 0.2 mEq/l and 58% had diabetes. Among nondiabetic individuals, per 0.1 mEq/l higher Mg, non-zero CAC score was lower (% difference: -15.4%; 95% confidence interval [CI]: -28% to -0.55%; P = 0.03), the odds of having TAC score >0 and the odds of having high ABI were lower (odds ratio [OR]: 0.66; 95% CI 0.47-0.93; P = 0.02, and 0.23; 95% CI: 0.06-0.83, P = 0.03, respectively) while adjusting for demographics, comorbidities, markers of mineral metabolism, and dialysis clearance. Among diabetic individuals, per 0.1 mEq/l higher Mg, the odds of having TAC score >0 was higher (OR: 1.57; 95% CI: 1.09-2.26; P = 0.02). Mg was not associated with CAC or high ABI among diabetic individuals. Mg was not associated with PWV or pulse pressure regardless of diabetes status.ConclusionDiabetes modified the associations of serum Mg with arterial calcification and stiffness in incident HD patients. Higher Mg was associated with less arterial calcification and less peripheral arterial stiffness among nondiabetic individuals, but Mg was only associated with TAC among diabetic individuals with higher Mg being associated with higher likelihood of having TAC score >0.

BackgroundFrail obese community-dwelling older adults are at increased mortality risk. Among hemodialysis (HD) patients, frailty is common and associated with increased mortality risk; however, in dialysis, obesity is associated with decreased mortality risk. Whether the frail-obese phenotype is associated with increased mortality risk among HD patients remains unclear.MethodsThis study included 370 incident HD patients enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study. We measured frailty using the Fried phenotype, general obesity [body mass index (BMI) ≥30 kg/m2] and abdominal obesity [waist:hip ratio (WHR) ≥median WHR] and estimated their associations with mortality.ResultsThe mean age was 55 years, with 42% female, 73% African American, 57% diabetic and 52% frail. Frail HD patients had higher mean BMI (frail = 30.3 kg/m2, non-frail = 28.3 kg/m2; P = 0.02) and similar WHR (P = 0.8). Twenty-two percent were frail with general obesity and 27% were frail with abdominal obesity. Frailty was associated with 1.66-fold increased mortality risk [95% confidence interval (CI) 1.03-2.67]. BMI was associated with a decreased mortality risk [25.0-29.9 kg/m2 hazard ratio (HR) 0.53 (95% CI 0.31-0.93); ≥30 kg/m2 HR 0.34 (95% CI 0.19-0.62)]. Frailty was associated with elevated mortality risk among HD patients with general [HR 3.77 (95% CI 1.10-12.92)] and abdominal obesity [HR 2.38 (95% CI 1.17-4.82)]. Frailty was not associated with mortality among HD patients without general or abdominal obesity.ConclusionsIn adults initiating HD, frailty was associated with elevated mortality risk, even among the obese. Frail-obese HD patients may be a high-risk, often-overlooked population, as obesity is assumed to be protective. Measurement of frailty and obesity may facilitate risk stratification.

Background An adequate workforce is needed to guarantee optimal kidney care. We used the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to provide an assessment of the global kidney care workforce. Methods We conducted a multinational cross-sectional survey to evaluate the global capacity of kidney care and assessed data on the number of adult and paediatric nephrologists, the number of trainees in nephrology and shortages of various cadres of the workforce for kidney care. Data are presented according to the ISN region and World Bank income categories. Results Overall, stakeholders from 167 countries responded to the survey. The median global prevalence of nephrologists was 11.75 per million population (pmp) (interquartile range [IQR] 1.78–24.76). Four regions had median nephrologist prevalences below the global median: Africa (1.12 pmp), South Asia (1.81 pmp), Oceania and Southeast Asia (3.18 pmp) and newly independent states and Russia (9.78 pmp). The overall prevalence of paediatric nephrologists was 0.69 pmp (IQR 0.03–1.78), while overall nephrology trainee prevalence was 1.15 pmp (IQR 0.18–3.81), with significant variations across both regions and World Bank income groups. More than half of the countries reported shortages of transplant surgeons (65%), nephrologists (64%), vascular access coordinators (59%), dialysis nurses (58%) and interventional radiologists (54%), with severe shortages reported in low- and lower-middle-income countries. Conclusions There are significant limitations in the available kidney care workforce in large parts of the world. To ensure the delivery of optimal kidney care worldwide, it is essential to develop national and international strategies and training capacity to address workforce shortages. [ABSTRACT FROM AUTHOR]

BACKGROUND:Advanced chronic kidney disease is associated with elevated risk for cognitive impairment. However, it is not known whether and how cognitive impairment is associated with planning and preparation for end-stage renal disease. STUDY DESIGN:Retrospective observational study. SETTING & PARTICIPANTS:630 adults participating in the CRIC (Chronic Renal Insufficiency Cohort) Study who had cognitive assessments in late-stage CKD, defined as estimated glome-rular filtration rate ≤ 20mL/min/1.73m2, and subsequently initiated maintenance dialysis therapy. PREDICTOR:Predialysis cognitive impairment, defined as a score on the Modified Mini-Mental State Examination lower than previously derived age-based threshold scores. Covariates included age, race/ethnicity, educational attainment, comorbid conditions, and health literacy. OUTCOMES:Peritoneal dialysis (PD) as first dialysis modality, preemptive permanent access placement, venous catheter avoidance at dialysis therapy initiation, and preemptive wait-listing for a kidney transplant. MEASUREMENTS:Multivariable-adjusted logistic regression. RESULTS:Predialysis cognitive impairment was present in 117 (19%) participants. PD was the first dialysis modality among 16% of participants (n=100), 75% had preemptive access placed (n=473), 45% avoided using a venous catheter at dialysis therapy initiation (n=279), and 20% were preemptively wait-listed (n=126). Predialysis cognitive impairment was independently associated with 78% lower odds of PD as the first dialysis modality (adjusted OR [aOR], 0.22; 95% CI, 0.06-0.74; P=0.02) and 42% lower odds of venous catheter avoidance at dialysis therapy initiation (aOR, 0.58; 95% CI, 0.34-0.98; P=0.04). Predialysis cognitive impairment was not independently associated with preemptive permanent access placement or wait-listing. LIMITATIONS:Potential unmeasured confounders; single measure of cognitive function. CONCLUSIONS:Predialysis cognitive impairment is associated with a lower likelihood of PD as a first dialysis modality and of venous catheter avoidance at dialysis therapy initiation. Future studies may consider addressing cognitive function when testing strategies to improve patient transitions to dialysis therapy.

BACKGROUND:Mortality in end-stage renal disease (ESRD) occurs predominantly from cardiovascular disease (CVD) and sudden cardiac death (SCD). Obstructive sleep apnea (OSA) is characterized by periodic airflow limitation associated with sleep arousal and oxygen desaturation and is prevalent in patients with ESRD. Whether OSA increases the risk for SCD, cardiovascular and all-cause mortality among hemodialysis patients remains unknown. METHODS:In a prospective cohort of 558 incident hemodialysis patients, we examined the association of OSA with all-cause mortality, cardiovascular mortality, and SCD using Cox proportional hazards models controlling for traditional CVD risk factors. RESULTS:Sixty-six incident hemodialysis patients (12%) had OSA. Mean age (56 years) and percentage of males (56%) were identical in OSA and no-OSA groups. Fewer African Americans had OSA than non-African Americans (9 vs. 18%, respectively). Participants with OSA had higher body-mass index, Charlson comorbidity score, and left ventricular mass index and greater prevalence of diabetes and coronary artery disease. During 1,080 person-years of follow-up, 104 deaths occurred, 29% of which were cardiovascular. OSA was associated with a higher risk of all-cause mortality (HR 1.90 [95% CI 1.04-3.46]) and cardiovascular mortality (HR 3.62 [95% CI 1.36-9.66]) after adjusting for demographics and body-mass index. OSA was associated with a higher risk of SCD after adjusting for demographics (HR 3.28 [95% CI 1.12-9.57]) and multiple cardiovascular risk factors. CONCLUSIONS:Incident hemodialysis patients with OSA are at increased risk of all-cause and cardiovascular mortality and SCD. Future studies should assess the impact of screening for OSA and OSA-targeted interventions on mortality in ESRD.

BackgroundThe risk of cardiovascular mortality is high among adults with end-stage renal disease (ESRD) undergoing hemodialysis. Waist-to-hip ratio (WHR), a metric of abdominal adiposity, is a predictor of cardiovascular disease (CVD) and mortality in the general population; however, no studies have examined the association with CVD mortality, particularly sudden cardiac death (SCD), in incident hemodialysis.MethodsAmong 379 participants incident (< 6 months) to hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in ESRD study, we evaluated associations between WHR and risk of CVD mortality, SCD, and non-CVD mortality in Cox proportional hazards regression models.ResultsAt study enrollment, mean age was 55 years with 41% females, 73% African Americans, and 57% diabetics. Mean body mass index was 29.3 kg/m2, and mean WHR was 0.95. During a median follow-up time of 2.5 years, there were 35 CVD deaths, 15 SCDs, and 48 non-CVD deaths. Every 0.1 increase in WHR was associated with higher risk (hazard ratio [95% CI]) of CVD mortality (1.75 [1.06-2.86]) and SCD (2.45 [1.20-5.02]), but not non-CVD mortality (0.93 [0.59-1.45]), independently of demographics, body mass index, comorbidities, inflammation, and traditional CVD risk factors.ConclusionsWHR is significantly associated with CVD mortality including SCD, independently of other CVD risk factors in incident hemodialysis. This simple, easily obtained bedside metric may be useful in dialysis patients for CVD risk stratification.

IntroductionChronic kidney disease (CKD) is associated with an increased risk of cognitive decline, but the mechanisms remain poorly defined. We sought to determine the relation between serum inflammatory markers and risk of cognitive decline among adults with CKD.MethodsWe studied 757 adults aged ≥55 years with CKD participating in the Chronic Renal Insufficiency Cohort Cognitive study. We measured interleukin (IL)-1β, IL-1 receptor antagonist, IL-6, tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein (hs-CRP), and fibrinogen in baseline plasma samples. We assessed cognitive function at regular intervals in 4 domains and defined incident impairment as a follow-up score more than 1 SD poorer than the group mean.ResultsThe mean age of the sample was 64.3 ± 5.6 years, and the mean follow-up was 6.2 ± 2.5 years. At baseline, higher levels of each inflammatory marker were associated with poorer age-adjusted performance. In analyses adjusted for baseline cognition, demographics, comorbid conditions, and kidney function, participants in the highest tertile of hs-CRP, the highest tertile of fibrinogen, and the highest tertile of IL-1β had an increased risk of impairment in attention compared to participants in the lowest tertile of each marker. Participants in the highest versus lowest tertile of TNF-α had a lower adjusted risk of impairment in executive function. There was no association between other inflammatory markers and change in cognitive function.DiscussionAmong adults with CKD, higher levels of hs-CRP, fibrinogen, and IL-1β were associated with a higher risk of impairment in attention. Higher levels of TNF-α were associated with a lower risk of impaired executive function.

BackgroundIntravenous iron use in hemodialysis patients has greatly increased over the last decade, despite limited studies on the safety of iron.MethodsWe studied the association of receipt of intravenous iron with hospitalizations in an incident cohort of hemodialysis patients. We examined 9544 patients from Dialysis Clinic, Inc. (DCI). We ascertained intravenous iron use from DCI electronic medical record and USRDS data files, and hospitalizations through Medicare claims. We examined the association between iron exposure accumulated over 1-, 3- or 6-month time windows and incident hospitalizations in the follow-up period using marginal structural models accounting for time-dependent confounders. We performed sensitivity analyses including recurrent events models for multiple hospitalizations and models for combined outcome of hospitalization and death.ResultsThere were 22 347 hospitalizations during a median follow-up of 23 months. Higher cumulative dose of intravenous iron was not associated with all-cause, cardiovascular or infectious hospitalizations [HR 0.97 (95% CI: 0.77-1.22) for all-cause hospitalizations comparing >2100 mg versus 0-900 mg of iron over 6 months]. Findings were similar in models examining the risk of hospitalizations in 1- and 3-month windows [HR 0.88 (95% CI: 0.79-0.99) and HR 0.88 (95% CI: 0.74-1.03), respectively] or the risk of combined outcome of hospitalization and death in the 6-month window [HR 0.98 (95% CI: 0.78-1.23)].ConclusionsHigher cumulative dose of intravenous iron may not be associated with increased risk of hospitalizations in hemodialysis patients. While clinical trials are needed, employing higher iron doses to reduce erythropoiesis-stimulating agents does not appear to increase morbidity in routine clinical care.

Background: There is uncertainty regarding treatment of hypertension in hemodialysis patients due to the observed J-shaped association between blood pressure (BP) and death. We hypothesized that this association reflects confounding by cardiovascular disease (CVD) and that stratification by CVD biomarkers, cardiac troponin I (cTnI) and N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP), might change this association. Study Design: National prospective cohort study. Setting & Participants: 446 incident hemodialysis patients. Predictor: Predialysis systolic BP. Outcomes: Mortality (all-cause and CVD) and first CVD event assessed using Cox regression adjusted for demographics, comorbid conditions, and clinical factors. Measurements: Participants with cTnI level ≥ 0.1 ng/mL or NT-proBNP level ≥ 9,252 pg/mL were classified as the high-biomarker group; remaining participants were included in the low-biomarker group. Results: Participants in the high-biomarker group (n = 138 [31%]) were older (61 vs 57 years) and had a higher prevalence of CVD (67% vs 23%), but similar baseline BPs (152 vs 153 mm Hg). There were 323 deaths (143 from CVD) and 271 CVD events. The high-biomarker group had a higher risk of mortality than the low-biomarker group (HR, 1.75; 95% CI, 1.37-2.24). The association between BP and outcomes differed between the 2 biomarker groups (P for interaction = 0.01, 0.2, and 0.07 for all-cause mortality, CVD mortality, and first CVD event, respectively). In the low-biomarker group, BP was associated with greater risk of outcomes: HR per 10 mm Hg higher BP was 1.07 (95% CI, 1.01-1.14), 1.10 (95% CI, 0.96-1.25), and 1.04 (95% CI, 0.96-1.13) for all-cause mortality, CVD mortality, and first CVD event, respectively. Importantly, lower BP was not associated with increased risk of outcomes in stratified models, including for those in high biomarker group. Limitations: BP measurements not standardized. Conclusions: The observed J-shaped association between BP and outcomes in hemodialysis patients is due to confounding by subclinical CVD. A stratification approach based on cTnI and NT-proBNP levels has the potential to inform BP treatment in hemodialysis patients. © 2014 National Kidney Foundation, Inc.

Abstract Background Evidence is lacking to inform providers’ and patients’ decisions about many common treatment strategies for patients with end stage renal disease (ESRD). Methods/design The DEcIDE Patient Outcomes in ESRD Study is funded by the United States (US) Agency for Health Care Research and Quality to study the comparative effectiveness of: 1) antihypertensive therapies, 2) early versus later initiation of dialysis, and 3) intravenous iron therapies on clinical outcomes in patients with ESRD. Ongoing studies utilize four existing, nationally representative cohorts of patients with ESRD, including (1) the Choices for Healthy Outcomes in Caring for ESRD study (1041 incident dialysis patients recruited from October 1995 to June 1999 with complete outcome ascertainment through 2009), (2) the Dialysis Clinic Inc (45,124 incident dialysis patients initiating and receiving their care from 2003–2010 with complete outcome ascertainment through 2010), (3) the United States Renal Data System (333,308 incident dialysis patients from 2006–2009 with complete outcome ascertainment through 2010), and (4) the Cleveland Clinic Foundation Chronic Kidney Disease Registry (53,399 patients with chronic kidney disease with outcome ascertainment from 2005 through 2009). We ascertain patient reported outcomes (i.e., health-related quality of life), morbidity, and mortality using clinical and administrative data, and data obtained from national death indices. We use advanced statistical methods (e.g., propensity scoring and marginal structural modeling) to account for potential biases of our study designs. All data are de-identified for analyses. The conduct of studies and dissemination of findings are guided by input from Stakeholders in the ESRD community. Discussion The DEcIDE Patient Outcomes in ESRD Study will provide needed evidence regarding the effectiveness of common treatments employed for dialysis patients. Carefully planned dissemination strategies to the ESRD community will enhance studies’ impact on clinical care and patients’ outcomes.