Faculty Bibliography

BACKGROUND:Sudden death accounts for ∼25% of deaths among maintenance hemodialysis (HD) patients, occurring more frequently on HD days. Higher dialysate bicarbonate (DBIC) may predispose to alkalemia and arrhythmogenesis. METHODS:We conducted a 12-month analysis of session-level data from 66 patients with implantable loop recorders. We fit logistic regression and negative binomial mixed effects regression models to assess the association of DBIC with clinically significant arrhythmia (CSA - ventricular tachycardia ≥115 beats per minute (BPM) for at least 30 seconds, bradycardia ≤40 BPM for at least 6 seconds, or asystole for at least 3 seconds) and reviewer confirmed arrhythmia (RCA - implantable-loop-recorder-identified or patient-marked event for which a manual review of the stored ECG tracing confirmed the presence of atrial fibrillation, supraventricular tachycardia, sinus tachycardia with rate >130 BPM, ventricular tachycardia, asystole, or bradycardia). Models adjusted for age, sex, race, HD vintage, vascular access, and pre-HD serum bicarbonate and additionally for serum and dialysate potassium levels. RESULTS:Mean age was 56 ± 12 years, 70% were male, 53% were Black, and 35% were Asian. Fewer RCA episodes were associated with DBIC >35 than 35 mEq/L (incidence rate ratio [IRR] 0.45 (0.27, 0.75) and aIRR 0.54 (0.30, 0.97)), but the association was not significant when adjusting for serum and dialysate potassium levels (aIRR 0.60 (0.32, 1.11)). Otherwise, no associations between DBIC and arrhythmia were identified. CONCLUSIONS:We observed a lower frequency of RCA with higher DBIC, compared with DBIC of 35 mEql/L, contrary to our original hypothesis, but this association was attenuated in fully adjusted models. Validation of these findings in larger studies is required, with a further need for interventional studies to explore the optimal DBIC concentration.

BACKGROUND:Chronic kidney disease (CKD) is highly prevalent, affecting approximately 11% of U.S. adults. Multiple studies have evaluated a potential association between CKD and urinary tract malignancies. Summary estimates of urinary tract malignancy risk in CKD patients with and without common co-existing conditions may guide clinical practice recommendations. METHODS:Four electronic databases were searched for original cohort studies evaluating the association between CKD and urinary tract cancers (kidney cancer and urothelial carcinoma) through May 25, 2023, in persons with at least moderate CKD and no dialysis or kidney transplantation. Quality assessment was performed for studies meeting inclusion criteria using the Newcastle-Ottawa Scale. Meta-analysis with a random-effects model was performed for unadjusted incidence rate ratios (IRR) as well as adjusted hazard ratios (aHR) for confounding conditions (diabetes, hypertension, and/or tobacco use), shown to have association with kidney cancer and urothelial carcinoma. Sub-analysis was conducted for estimates associated with CKD stages separately. RESULTS:Six cohort studies with 8 617 563 persons were included. Overall, methodological quality of the studies was good. CKD was associated with both higher unadjusted incidence and adjusted hazard of kidney cancer (IRR, 3.36; 95% confidence interval [CI], 2.32-4.88; aHR, 2.04; 95% CI, 1.77-2.36) and urothelial cancer (IRR, 3.96; 95% CI, 2.44-6.40; aHR, 1.40; 95% CI, 1.22-1.68) compared with persons without CKD. Examining incident urinary tract cancers by CKD severity, risks were elevated in stage 3 CKD (kidney aHR, 1.89; 95% CI, 1.56-2.30; urothelial carcinoma aHR, 1.40; 95% CI, 1.18-1.65) as well as in stages 4/5 CKD (kidney cancer aHR, 2.30; 95% CI, 2.00-2.66, UC aHR, 1.24; 95% CI, 1.04-1.49). CONCLUSIONS:Even moderate CKD is associated with elevated risk of kidney cancer and UC. Providers should consider these elevated risks when managing individuals with CKD, particularly when considering evaluation for the presence and etiology of hematuria.

The risk of arrhythmia and its management become increasingly complex as kidney disease progresses. This presents a multifaceted clinical challenge. Our discussion addresses these specific challenges relevant to patients as their kidney disease advances. We highlight numerous opportunities for enhancing the current standard of care within this realm. Additionally, this review delves into research concerning early detection, prevention, diagnosis, and treatment of various arrhythmias spanning the spectrum of kidney disease.

RATIONALE & OBJECTIVE/UNASSIGNED:The incidence of arrhythmia varies by time of day. How this affects individuals on maintenance dialysis is uncertain. Our objective was to quantify the relationship of arrhythmia with the time of day and timing of dialysis. STUDY DESIGN/UNASSIGNED:Secondary analysis of the Monitoring in Dialysis study, a multicenter prospective cohort study. SETTINGS & PARTICIPANTS/UNASSIGNED:Loop recorders were implanted for continuous cardiac monitoring in 66 participants on maintenance dialysis with a follow up of 6 months. EXPOSURE/UNASSIGNED:Time of day based on 6-hour intervals. OUTCOMES/UNASSIGNED:Event rates of clinically significant arrhythmia. ANALYTICAL APPROACH/UNASSIGNED:Negative binomial mixed effects regression models for repeated measures were used to evaluate data from the Monitoring in Dialysis study for differences in diurnal patterns of clinically significant arrhythmia among those with end-stage kidney disease with heart failure and end-stage kidney disease alone. We additionally analyzed rates according to presence of heart failure, time of dialysis shift, and dialysis versus nondialysis day. RESULTS/UNASSIGNED: = 0.43), their periodicity differed with a peak between 12:00 AM and 5:59 AM in those with AM dialysis and a later peak between 6:00 AM and 11:59 AM in those with PM shifts. LIMITATIONS/UNASSIGNED:Post hoc analysis, unable to account for unmeasured confounders. CONCLUSION/UNASSIGNED:Clinically significant arrhythmias showed strong diurnal patterns with a maximal peak between 12:00 AM and 5:59 AM and noon. Although overall arrhythmia rates were similar, the peak rate occurred overnight in individuals without heart failure and during the morning in individuals with heart failure. Further exploration of the influence of circadian rhythm on arrhythmia in the setting of hemodialysis is needed.

BACKGROUND:Chronic kidney disease (CKD) has been implicated as a risk factor for venous thromboembolism, but the evidence is limited to relatively healthy populations. The objective of the current study was to discern whether parameters of kidney function and damage are associated with the occurrence of venous thromboembolism after hospitalization. METHODS:We conducted a retrospective study including 23,899 and 11,552 adult individuals hospitalized within Geisinger Health System and NYU Langone Health from 2004 to 2019 and 2012 to 2022, respectively. A Poisson model was used to evaluate adjusted incidence rates of venous thromboembolism according to estimated glomerular filtration rate (eGFR) and albuminuria categories in each cohort. Cox proportional hazards models were used to analyze associations of eGFR and urinary albumin to creatinine ratio (UACR) with venous thromboembolism and hazard ratios were meta-analyzed across cohorts. RESULTS:Both lower eGFR and higher UACR were associated with higher risks of venous thromboembolism. In the Geisinger cohort, the incidence of venous thromboembolism after hospital discharge ranged from 10.7 (95% CI 9.2 - 12.6) events per 1000 person-years in individuals in G1A1 (eGFR >90 mL/min/1.73 m2 and UACR <30 mg/g) to 27.7 (95% CI 20.6 - 37.2) events per 1000 person-years in individuals with G4-5A3 (eGFR <30 mL/min/1.73 m2 and UACR >300 mg/g). A similar pattern was observed in the NYU cohort. Meta-analyses of the two cohorts showed that every 10 mL/min/1.73m2 reduction in eGFR below 60 mL/min/1.73m2 was associated with a 6% higher risk of venous thromboembolism (HR 1.06 [1.02 - 1.11], P = 0.01), and each two-fold higher UACR was associated with a 5% higher risk of venous thromboembolism (HR 1.05 [1.03 - 1.07], P <0.001). CONCLUSIONS:Both eGFR and UACR were independently associated with higher risk of venous thromboembolism after hospitalization. The incidence rate was higher with greater severity of CKD.

RATIONALE & OBJECTIVE/UNASSIGNED:This study aimed to assess the effect of exposure to organic pollutants in adults with chronic kidney disease (CKD). STUDY DESIGN/UNASSIGNED:This was a cross-sectional and longitudinal analysis. SETTING AND PARTICIPANTS/UNASSIGNED:Forty adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC). EXPOSURES/UNASSIGNED:Exposure at baseline and longitudinally to various organic chemical pollutants. OUTCOMES/UNASSIGNED:The outcomes were as follows: death; composite of congestive heart failure, myocardial infarction, and stroke; event-free survival from kidney failure or ≥50% decline in estimated glomerular filtration rate (eGFR); and longitudinal trajectory of eGFR. ANALYTICAL APPROACH/UNASSIGNED:We used high-performance liquid chromatography with tandem mass spectrometry to measure urinary concentrations of bisphenols, phthalates, organophosphate pesticides, polycyclic aromatic hydrocarbons, melamine, and cyanuric acid at years 1, 3, and 5 after enrollment in the CRIC. Univariate and multivariable logistic regression were used to examine the association of individual compounds and classes of pollutants with the outcomes. The Cox proportional hazards model and Kaplan-Meier method were used to calculate hazard ratios and 95% CIs for each class of pollutants. RESULTS/UNASSIGNED:and 0.58 mg/g, respectively. Of 52 compounds assayed, 30 were detectable in ≥50% of participants. Urinary chemical concentrations were comparable in patients with CKD and healthy individuals from contemporaneous National Health and Nutrition Examination Survey cohorts. Phthalates were the only class with a trend toward higher exposure in patients with CKD. There was an inverse relationship between exposure and the eGFR slopes for bisphenol F, mono-(3-carboxypropyl) phthalate, mono-benzyl phthalate, mono-[2-(carboxymethyl)hexyl] phthalate, and melamine. There were no associations between organic pollutant exposure and cardiovascular outcomes. LIMITATIONS/UNASSIGNED:Small sample size, evaluation of single rather than combined exposures. CONCLUSIONS/UNASSIGNED:Simultaneous measurement of multiple organic pollutants in adults with CKD is feasible. Exposure levels are comparable with healthy individuals. Select contaminants, especially in the phthalate class, may be associated with more rapid deterioration in kidney function.

The HOPE Consortium Trial to Reduce Pain and Opioid Use in Hemodialysis (HOPE Trial) is a multicenter randomized trial addressing chronic pain among patients receiving maintenance hemodialysis for end-stage kidney disease. The trial uses a sequential, multiple assignment design with a randomized component for all participants (Phase 1) and a non-randomized component for a subset of participants (Phase 2). During Phase 1, participants are randomized to Pain Coping Skills Training (PCST), an intervention designed to increase self-efficacy for managing pain, or Usual Care. PCST consists of weekly, live, coach-led cognitive behavioral therapy sessions delivered by video- or tele-conferencing for 12 weeks followed by daily interactive voice response sessions delivered by telephone for an additional 12 weeks. At 24 weeks (Phase 2), participants in both the PCST and Usual Care groups taking prescription opioid medications at an average dose of ≥20 morphine milligram equivalents per day are offered buprenorphine, a partial opioid agonist with a more favorable safety profile than full-agonist opioids. All participants are followed for 36 weeks. The primary outcome is pain interference ascertained at 12 weeks for the primary analysis. Secondary outcomes include additional patient-reported measures and clinical outcomes including falls, hospitalizations, and death. Exploratory outcomes include acceptability, tolerability, and efficacy of buprenorphine. The enrollment target of 640 participants was met 27 months after trial initiation. The findings of the trial will inform the management of chronic pain, a common and challenging issue for patients treated with maintenance hemodialysis. NCT04571619.

KEY POINTS:Women are under-represented in high-impact nephrology trials. Trends remain consistent over the past 20 years and on the basis of target condition. Addressing the imbalanced enrollment of women in trials could improve disparities in care and outcomes of kidney disease. BACKGROUND:Gender disparities in the incidence and complications of kidney diseases are well described. However, analysis to elucidate gender disparities in enrollment in nephrology randomized clinical trials (RCTs) has not been performed. METHODS:) kidney transplantation. We summarized trial characteristics according to reporting and enrollment of participants, enrollment site, publication year, trial category, and intervention type. Outcomes of interest include the proportion of enrolled male and female participants overall and according to trial category. In addition, we compared enrollment trends in the United States and globally to estimates of kidney disease prevalence. RESULTS:=133,082). Male participants formed most of trial cohorts in AKI (65%), CKD (62%), dialysis (55%), and transplant trials (65%), whereas women were majority enrollees in GN trials (61%). CKD trials under-represented women in both US trials and worldwide. CONCLUSIONS:Women are under-represented in high-impact nephrology trials with the exception of GN trials. This imbalance may contribute to disparities in outcomes and gaps in the care of women with kidney disease.

INTRODUCTION/UNASSIGNED:Chronic kidney disease (CKD) and left ventricular (LV) dysfunction are risk factors for cardiovascular events. We explore whether the association of LV ejection fraction (LVEF) with cardiac arrest, heart failure hospitalization, and all-cause mortality differs across stages of kidney impairment. METHODS/UNASSIGNED:and without end-stage kidney disease (ESKD). Cox regression models, incorporating an interaction term for eGFR and LVEF, were fit and adjusted for relevant covariates. RESULTS/UNASSIGNED:-interaction 0.26). CONCLUSION/UNASSIGNED:, the association of LVEF with cardiac arrest and heart failure hospitalization is attenuated at lower levels of kidney function. Further research is required to elucidate what factors beyond LVEF drive these observations.