Dialysis for Chronic Kidney Failure: A Review.

Importance: More than 3.5 million people worldwide and 540 000 individuals in the US receive maintenance hemodialysis or peritoneal dialysis for the treatment of chronic kidney failure. The 5-year survival rate is approximately 40% after initiation of maintenance dialysis. Observations: Hemodialysis and peritoneal dialysis remove metabolic waste and excess body water and rebalance electrolytes to sustain life. There is no recommended estimated glomerular filtration rate (eGFR) threshold for initiating dialysis, and patient-clinician shared decision-making should help determine when to initiate dialysis. Persistent signs and symptoms of uremia (eg, nausea, fatigue) and volume overload (eg, dyspnea, peripheral edema), worsening eGFR, metabolic acidosis, and hyperkalemia inform the timing of therapy initiation. A randomized clinical trial reported no mortality benefit to starting dialysis at higher eGFR (10-14 mL/min/1.73 m2) vs lower eGFR (5-7 mL/min/1.73 m2) levels. Observational data suggested no differences in 5-year mortality with use of hemodialysis vs peritoneal dialysis. Cardiovascular (eg, arrhythmias, cardiac arrest) and infection-related complications of maintenance dialysis are common. In the US, hemodialysis catheter-related bloodstream infections occur at a rate of 1.1 to 5.5 episodes per 1000 catheter-days and affect approximately 50% of patients within 6 months of catheter placement. Peritonitis occurs at a rate of 0.26 episodes per patient-year and affects about 30% of individuals in the first year of peritoneal dialysis therapy. Chronic kidney failure-related systemic complications, such as anemia, hyperphosphatemia, hypocalcemia, and hypertension, often require pharmacologic treatment. Hypotension during dialysis, refractory symptoms (eg, muscle cramps, itching), and malfunction of dialysis access can interfere with delivery of dialysis. Conclusions and Relevance: In 2021, more than 540 000 patients in the US received maintenance hemodialysis or peritoneal dialysis for treatment of chronic kidney failure. Five-year survival rate after initiation of maintenance dialysis is approximately 40%, and the mortality rate is similar with hemodialysis and peritoneal dialysis. Decisions about dialysis initiation timing and modality are influenced by patient symptoms, laboratory trajectories, patient preferences, and therapy cost and availability and should include shared decision-making.

Managing the symptom burden associated with maintenance dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Individuals with kidney failure undergoing maintenance dialysis frequently report a high symptom burden that can interfere with functioning and diminish life satisfaction. Until recently, the focus of nephrology care for dialysis patients has been related primarily to numerical targets for laboratory measures, and outcomes such as cardiovascular disease and mortality. Routine symptom assessment is not universal or standardized in dialysis care. Even when symptoms are identified, treatment options are limited and are initiated infrequently, in part because of a paucity of evidence in the dialysis population and the complexities of medication interactions in kidney failure. In May of 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference-Symptom-Based Complications in Dialysis-to identify the optimal means for diagnosing and managing symptom-based complications in patients undergoing maintenance dialysis. Participants included patients, physicians, behavioral therapists, nurses, pharmacists, and clinical researchers. They outlined foundational principles and consensus points related to identifying and addressing symptoms experienced by patients undergoing dialysis and described gaps in the knowledge base and priorities for research. Healthcare delivery and education systems have a responsibility to provide individualized symptom assessment and management. Nephrology teams should take the lead in symptom management, although this does not necessarily mean taking ownership of all aspects of care. Even when options for clinical response are limited, clinicians should focus on acknowledging, prioritizing, and managing symptoms that are most important to individual patients. A recognized factor in the initiation and implementation of improvements in symptom assessment and management is that they will be based on locally existing needs and resources.

Patient-Centered Quality Measures for Dialysis Care: A Report of a Kidney Disease Outcomes Quality Initiative (KDOQI) Scientific Workshop Sponsored by the National Kidney Foundation.

Providing high-quality patient-centered care is the central mission of dialysis facilities. Assessing quality and patient-centeredness of dialysis care is necessary for continuous dialysis facility improvement. Based predominantly on readily measured items, current quality measures in dialysis care emphasize biochemical and utilization outcomes, with very few patient-reported items. Additionally, current metrics often do not account for patient preferences and may compromise patient-centered care by limiting the ability of providers to individualize care targets, such as dialysis adequacy, based on patient priorities rather than a fixed numerical target. Developing, implementing, and maintaining a quality program using readily quantifiable data while also allowing for individualization of care targets that emphasize the goals of patients and their care partners provided the motivation for a September 2022 Kidney Disease Outcomes Quality Initiative (KDOQI) Workshop on Patient-Centered Quality Measures for Dialysis Care. Workshop participants focused on 4 questions: (1) What are the outcomes that are most important to patients and their care partners? (2) How can social determinants of health be accounted for in quality measures? (3) How can individualized care be effectively addressed in population-level quality programs? (4) What are the optimal means for collecting valid and robust patient-reported outcome data? Workshop participants identified numerous gaps within the current quality system and favored a conceptually broader, but not larger, quality system that stresses highly meaningful and adaptive measures that incorporate patient-centered principles, individual life goals, and social risk factors. Workshop participants also identified a need for new, low-burden tools to assess patient goals and priorities.

High-calorie diet results in reversible obesity-related glomerulopathy in adult zebrafish regardless of dietary fat.

Obesity is a risk factor for the development of kidney disease. The role of diet in this association remains undetermined, in part due to practical limitations in studying nutrition in humans. In particular, the relative importance of calorie excess versus dietary macronutrient content is poorly understood. For example, it is unknown if calorie restriction modulates obesity-related kidney pathology. To study the effects of diet-induced obesity in a novel animal model, we treated zebrafish for 8 wk with diets varied in both calorie and fat content. Kidneys were evaluated by light and electron microscopy. We evaluated glomerular filtration barrier function using a dextran permeability assay. We assessed the effect of diet on podocyte sensitivity to injury using an inducible podocyte injury model. We then tested the effect of calorie restriction on the defects caused by diet-induced obesity. Fish fed a high-calorie diet developed glomerulomegaly (mean: 1,211 vs. 1,010 µm2 in controls, P = 0.007), lower podocyte density, foot process effacement, glomerular basement membrane thickening, tubular enlargement (mean: 1,038 vs. 717 µm2 in controls, P < 0.0001), and ectopic lipid deposition. Glomerular filtration barrier dysfunction and increased susceptibility to podocyte injury were observed with high-calorie feeding regardless of dietary fat content. These pathological changes resolved with 4 wk of calorie restriction. Our findings suggest that calorie excess rather than dietary fat drives obesity-related kidney dysfunction and that inadequate podocyte proliferation in response to glomerular enlargement may cause podocyte dysfunction. We also demonstrate the value of zebrafish as a novel model for studying diet in obesity-related kidney disease.NEW & NOTEWORTHY Obesity is a risk factor for kidney disease. The role of diet in this association is difficult to study in humans. In this study, zebrafish fed a high-calorie diet, regardless of fat macronutrient composition, developed glomerulomegaly, foot process effacement, and filtration barrier dysfunction, recapitulating the changes seen in humans with obesity. Calorie restriction reversed the changes. This work suggests that macronutrient composition may be less important than total calories in the development of obesity-related kidney disease.

Azithromycin use increases the risk of sudden cardiac death in patients with hemodialysis-dependent kidney failure.

Azithromycin is an antibiotic with QT-prolonging potential commonly prescribed to individuals receiving hemodialysis. Hemodialysis patients have a high prevalence of clinical conditions, such as structural heart disease, that can enhance the pro-arrhythmic effects azithromycin, but were excluded from prior investigations evaluating the cardiac safety of azithromycin. Using data from the United States Renal Data System (2007-2017), we conducted two cohort studies to examine the cardiac safety of azithromycin relative to amoxicillin-based antibiotics (amoxicillin, amoxicillin/clavulanic acid) and levofloxacin (a fluoroquinolone antibiotic known to prolong the QT-interval) in the hemodialysis population. The primary outcome was five-day sudden cardiac death. Using inverse probability of treatment weighted survival models, we estimated hazard ratios, risk differences, and 95% confidence intervals. The azithromycin vs. amoxicillin-based antibiotic cohort included 282,899 patients and 725,431 treatment episodes (381,306 azithromycin and 344,125 amoxicillin-based episodes). Azithromycin vs. amoxicillin-based antibiotic treatment was associated with higher relative and absolute risks of sudden cardiac death, weighted hazard ratio of 1.70 (95% Confidence Interval, 1.36 to 2.11) and weighted risk difference per 100,000 treatment episodes of 25.0 (15.5 to 36.5). The azithromycin vs. levofloxacin cohort included 245,143 patients and 554,557 treatment episodes (387,382 azithromycin and 167,175 levofloxacin episodes). Azithromycin vs. levofloxacin treatment was associated with lower relative and absolute risks of sudden cardiac death, weighted hazard ratio of 0.79 (0.64 to 0.96) and weighted risk difference per 100,000 treatment episodes of -18.9 (-35.5 to -3.8). Thus, when selecting among azithromycin, levofloxacin, and amoxicillin-based antibiotics, clinicians should weigh the relative antimicrobial benefits of these drugs against their potential cardiac risks.

Kidney dysfunction requiring dialysis is a heterogeneous syndrome: we should treat it like one.

PURPOSE OF REVIEW: Advanced kidney failure requiring dialysis, commonly labeled end-stage kidney disease or chronic kidney disease stage 5D, is a heterogeneous syndrome -a key reason that may explain why: treating advanced kidney dysfunction is challenging and many clinical trials involving patients on dialysis have failed, thus far. Treatment with dialytic techniques - of which maintenance thrice-weekly hemodialysis is most commonly used - is broadly named kidney 'replacement' therapy, a term that casts the perception of a priori abandonment of intrinsic kidney function and subsumes patients into a single, homogeneous group. RECENT FINDINGS: Patients with advanced kidney failure necessitating dialytic therapy may have ongoing endogenous kidney function, and differ in their clinical manifestations and needs. Different terminology, for example, kidney dysfunction requiring dialysis (KDRD) with stages of progressive severity could better capture the range of phenotypes of patients who require kidney 'assistance' therapy. SUMMARY: Classifying patients with KDRD based on objective, quantitative levels of endogenous kidney function, as well as patient-reported symptoms and quality of life, would facilitate hemodialysis prescriptions tailored to level of kidney dysfunction, clinical needs, and personal priorities. Such classification would encourage clinicians to move toward personalized, physiological, and adaptive approach to hemodialysis therapy.

Association Between Long-term Ambient PM2.5 Exposure and Cardiovascular Outcomes Among US Hemodialysis Patients.

RATIONALE & OBJECTIVE: Ambient PM2.5 (particulate matter with a diameter of 2.5 microns) is a ubiquitous air pollutant with established adverse cardiovascular (CV) effects. However, quantitative estimates of the association between PM2.5 exposure and CV outcomes in the setting of kidney disease are limited. This study assessed the association of long-term PM2.5 exposure with CV events and cardiovascular disease (CVD)-specific mortality among patients receiving maintenance in-center hemodialysis (HD). STUDY DESIGN: Retrospective cohort study. SETTINGS & PARTICIPANTS: 314,079 adult kidney failure patients initiating HD between 2011 and 2016 identified from the US Renal Data System. EXPOSURE: Estimated daily ZIP code-level PM2.5 concentrations were used to calculate each participant's annual average PM2.5 exposure based on the dialysis clinics visited during the 365 days before the outcome. OUTCOME: CV event and CVD-specific mortality were ascertained based on ICD-9/ICD-10 diagnostic codes and recorded cause of death from Centers for Medicare & Medicaid Services form 2746. ANALYTICAL APPROACH: Discrete time hazards models were used to estimate hazards ratios per 1 µg/m3 greater annual average PM2.5, adjusting for temperature, humidity, day of the week, season, age at baseline, race, employment status, and geographic region. Effect measure modification was assessed for age, sex, race, and baseline comorbidities. RESULTS: Each 1 µg/m3 greater annual average PM2.5 was associated with a greater rate of CV events (HR, 1.02 [95% CI, 1.01-1.02]) and CVD-specific mortality (HR, 1.02 [95% CI, 1.02-1.03]). The association was more pronounced for people who initiated dialysis at an older age, had chronic obstructive pulmonary disease (COPD) at baseline, or were Asian. Evidence of effect modification was also observed across strata of race, and other baseline comorbidities. LIMITATIONS: Potential exposure misclassification and unmeasured confounding. CONCLUSIONS: Long-term ambient PM2.5 exposure was associated with CVD outcomes among patients receiving maintenance in-center HD. Stronger associations between long-term PM2.5 exposure and adverse effects were observed among patients who were of advanced age, had COPD, or were Asian. PLAIN-LANGUAGE SUMMARY: Long-term exposure to air pollution, also called PM2.5, has been linked to adverse cardiovascular outcomes. However, little is known about the association of PM2.5 and outcomes among patients receiving dialysis, who are individuals with high cardiovascular disease burdens. We conducted an epidemiological study to assess the association between the annual PM2.5 exposure and cardiovascular events and death among patients receiving regular outpatient hemodialysis in the United States between 2011 and 2016. We found a higher risk of heart attacks, strokes, and related events in patients exposed to higher levels of air pollution. Stronger associations between air pollution and adverse health events were observed among patients who were older at the start of dialysis, had chronic obstructive pulmonary disease, or were Asian. These findings bolster the evidence base linking air pollution and adverse health outcomes and may inform policy makers and clinicians.

The modifying effect of the serum-to-dialysate potassium gradient on the cardiovascular safety of SSRIs in the hemodialysis population: a pharmacoepidemiologic study.

BACKGROUND: Hypokalemia is a risk factor for drug-induced QT prolongation. Larger serum-to-dialysate potassium gradients during hemodialysis (HD) may augment the proarrhythmic risks of selective serotonin reuptake inhibitors (SSRIs). METHODS: We conducted a cohort study using 2007-2017 data from the United States Renal Data System and a large dialysis provider to examine if the serum-to-dialysate potassium gradient modifies SSRI cardiac safety. Using a new-user design, we compared 1-year sudden cardiac death (SCD) risk among HD patients newly treated with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) QT-prolonging potential SSRIs, overall and stratified by baseline potassium gradient (≥4 versus <4 mEq/l). We used inverse probability of treatment-weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) and conducted a confirmatory nested case-control study. RESULTS: The study included 25 099 patients: 11 107 (44.3%) higher QT-prolonging potential SSRI new users and 13 992 (55.7%) lower QT-prolonging potential SSRI new users. Overall, higher versus lower QT-prolonging potential SSRI use was not associated with SCD [weighted HR 1.03 (95% CI 0.86-1.24)]. However, a greater risk of SCD was associated with higher versus lower QT-prolonging potential SSRI use among patients with baseline potassium gradients ≥4 mEq/l but not among those with gradients <4 mEq/l [weighted HR 2.17 (95% CI 1.16-4.03) versus 0.95 (0.78-1.16)]. Nested case-control analyses yielded analogous results. CONCLUSIONS: The serum-to-dialysate potassium gradient may modify the association between higher versus lower QT-prolonging SSRI use and SCD among people receiving HD. Minimizing the potassium gradient in the setting of QT-prolonging medication use may be warranted.

Proton pump inhibitors may enhance the risk of citalopram- and escitalopram-associated sudden cardiac death among patients receiving hemodialysis.

PURPOSE: Polypharmacy is common in the hemodialysis population and increases the likelihood that patients will be exposed to clinically significant drug-drug interactions. Concurrent use of proton pump inhibitors (PPIs) with citalopram or escitalopram may potentiate the QT-prolonging effects of these selective serotonin reuptake inhibitors through pharmacodynamic and/or pharmacokinetic interactions. METHODS: We conducted a retrospective cohort study using data from the U.S. Renal Data System (2007-2017) and a new-user design to examine the differential risk of sudden cardiac death (SCD) associated with citalopram/escitalopram initiation vs. sertraline initiation in the presence and absence of PPI use among adults receiving hemodialysis. We studied 72 559 patients:14 983 (21%) citalopram/escitalopram initiators using a PPI; 26 503 (36%) citalopram/escitalopram initiators not using a PPI;10 779 (15%) sertraline initiators using a PPI; and 20 294 (28%) sertraline initiators not using a PPI (referent). The outcome of interest was 1-year SCD. We used inverse probability of treatment weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with sertraline initiators not using a PPI, citalopram/escitalopram initiators using a PPI had the numerically highest risk of SCD (HR [95% CI] = 1.31 [1.11-1.54]), followed by citalopram/escitalopram initiators not using a PPI (HR [95% CI] = 1.22 [1.06-1.41]). Sertraline initiators using a PPI had a similar risk of SCD compared with those not using a PPI (HR [95% CI] = 1.03 [0.85-1.26]). CONCLUSIONS: Existing PPI use may elevate the risk of SCD associated with citalopram or escitalopram initiation among hemodialysis patients.

Effects of short-term ambient PM2.5 exposure on cardiovascular disease incidence and mortality among U.S. hemodialysis patients: a retrospective cohort study.

BACKGROUND: Ambient PM2.5 is a ubiquitous air pollutant with demonstrated adverse health impacts in population. Hemodialysis patients are a highly vulnerable population and may be particularly susceptible to the effects of PM2.5 exposure. This study examines associations between short-term PM2.5 exposure and cardiovascular disease (CVD) and mortality among patients receiving maintenance in-center hemodialysis. METHODS: Using the United State Renal Data System (USRDS) registry, we enumerated a cohort of all US adult kidney failure patients who initiated in-center hemodialysis between 1/1/2011 and 12/31/2016. Daily ambient PM2.5 exposure estimates were assigned to cohort members based on the ZIP code of the dialysis clinic. CVD incidence and mortality were ascertained through 2016 based on USRDS records. Discrete time hazards regression was used to estimate the association between lagged PM2.5 exposure and CVD incidence, CVD-specific mortality, and all-cause mortality 1 t adjusting for temperature, humidity, day of the week, season, age at baseline, race, employment status, and geographic region. Effect measure modification was assessed for age, sex, race, and comorbidities. RESULTS: Among 314,079 hemodialysis patients, a 10 µg/m3 increase in the average lag 0-1 daily PM2.5 exposure was associated with CVD incidence (HR: 1.03 (95% CI: 1.02, 1.04)), CVD mortality (1.05 (95% CI: 1.03, 1.08)), and all-cause mortality (1.04 (95% CI: 1.03, 1.06)). The association was larger for people who initiated dialysis at an older age, while minimal evidence of effect modification was observed across levels of sex, race, or baseline comorbidities. CONCLUSIONS: Short-term ambient PM2.5 exposure was positively associated with incident CVD events and mortality among patients receiving in-center hemodialysis. Older patients appeared to be more susceptible to PM2.5-associated CVD events than younger hemodialysis patients.

Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19.

BACKGROUND: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. DESIGN: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. SETTING: 67 hospitals in the United States. PARTICIPANTS: Adults with COVID-19 admitted to a participating ICU. MEASUREMENTS: Time to death, censored at hospital discharge, or date of last follow-up. RESULTS: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). LIMITATION: Observational design. CONCLUSION: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. PRIMARY FUNDING SOURCE: None.

AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-19.

BACKGROUND: AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT). METHODS: We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients. RESULTS: A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1-123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission. CONCLUSIONS: AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission.

Characteristics and Outcomes of Individuals With Pre-existing Kidney Disease and COVID-19 Admitted to Intensive Care Units in the United States.

RATIONALE & OBJECTIVE: Underlying kidney disease is an emerging risk factor for more severe coronavirus disease 2019 (COVID-19) illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing chronic kidney disease (CKD) and investigated the association between the degree of underlying kidney disease and in-hospital outcomes. STUDY DESIGN: Retrospective cohort study. SETTINGS & PARTICIPANTS: 4,264 critically ill patients with COVID-19 (143 patients with pre-existing kidney failure receiving maintenance dialysis; 521 patients with pre-existing non-dialysis-dependent CKD; and 3,600 patients without pre-existing CKD) admitted to intensive care units (ICUs) at 68 hospitals across the United States. PREDICTOR(S): Presence (vs absence) of pre-existing kidney disease. OUTCOME(S): In-hospital mortality (primary); respiratory failure, shock, ventricular arrhythmia/cardiac arrest, thromboembolic events, major bleeds, and acute liver injury (secondary). ANALYTICAL APPROACH: We used standardized differences to compare patient characteristics (values>0.10 indicate a meaningful difference between groups) and multivariable-adjusted Fine and Gray survival models to examine outcome associations. RESULTS: Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median of 4 [IQR, 2-9] days for maintenance dialysis patients; 7 [IQR, 3-10] days for non-dialysis-dependent CKD patients; and 7 [IQR, 4-10] days for patients without pre-existing CKD). More dialysis patients (25%) reported altered mental status than those with non-dialysis-dependent CKD (20%; standardized difference=0.12) and those without pre-existing CKD (12%; standardized difference=0.36). Half of dialysis and non-dialysis-dependent CKD patients died within 28 days of ICU admission versus 35% of patients without pre-existing CKD. Compared to patients without pre-existing CKD, dialysis patients had higher risk for 28-day in-hospital death (adjusted HR, 1.41 [95% CI, 1.09-1.81]), while patients with non-dialysis-dependent CKD had an intermediate risk (adjusted HR, 1.25 [95% CI, 1.08-1.44]). LIMITATIONS: Potential residual confounding. CONCLUSIONS: Findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies in this vulnerable population.

Ultrafiltration rate and incident atrial fibrillation among older individuals initiating hemodialysis.

BACKGROUND: Higher ultrafiltration (UF) rates are associated with numerous adverse cardiovascular outcomes among individuals receiving maintenance hemodialysis. We undertook this study to investigate the association of UF rate and incident atrial fibrillation in a large, nationally representative US cohort of incident, older hemodialysis patients. METHODS: We used the US Renal Data System linked to the records of a large dialysis provider to identify individuals ≥67 years of age initiating hemodialysis between January 2006 and December 2011. We applied an extended Cox model as a function of a time-varying exposure to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of delivered UF rate and incident atrial fibrillation. RESULTS: Among the 15 414 individuals included in the study, 3177 developed atrial fibrillation. In fully adjusted models, a UF rate >13 mL/h/kg (versus ≤13 mL/h/kg) was associated with a higher hazard of incident atrial fibrillation [adjusted HR 1.19 (95% CI 1.07-1.30)]. Analyses using lower UF rate thresholds (≤10 versus >10 mL/h/kg and ≤8 versus >8 mL/h/kg, separately) yielded similar results. Analyses specifying the UF rate as a cubic spline (per 1 mL/h/kg) confirmed an approximately linear dose-response relationship between the UF rate and the risk of incident atrial fibrillation: risk began at UF rates of ~6 mL/h/kg and the magnitude of this risk flattened, but remained elevated, at rates ≥9 mL/h/kg. CONCLUSION: In this observational study of older individuals initiating hemodialysis, higher UF rates were associated with higher incidences of atrial fibrillation.

Development of a preliminary conceptual model of the patient experience of chronic kidney disease: a targeted literature review and analysis.

BACKGROUND: Patient-reported outcome (PRO) instruments should capture the experiences of disease and treatment that patients consider most important in order to inform patient-centred care and product development. The aim of this study was to develop a preliminary conceptual model of patient experience in chronic kidney disease (CKD) based on a targeted literature review and to characterize existing PRO instruments used in CKD. METHODS: PubMed, EMBASE and Cochrane databases and recent society meetings were searched for publications reporting signs/symptoms and life impacts of CKD. Concepts identified in the literature review were used to develop a preliminary conceptual model of patient experience of CKD, overall, and within patient subpopulations of differing CKD causes, severities and complications. PRO instruments, identified from PRO databases, CKD literature and CKD clinical trials, were assessed for content validity, psychometric strength and coverage of concepts in the literature review. RESULTS: In total, 100 publications met criteria for analysis; 56 signs/symptoms and 37 life impacts of CKD were identified from these sources. The most frequently mentioned signs/symptoms were pain/discomfort (57% of publications) and tiredness/low energy/lethargy/fatigue (42%); the most commonly reported life impacts were anxiety/depression (49%) and decrements in physical functioning (43%). Signs/symptoms and life impacts varied across the subpopulations and were more frequent at advanced CKD stages. The preliminary conceptual model grouped signs/symptoms into seven domains (pain/discomfort; energy/fatigue; sleep-related; gastrointestinal-related; urinary-related; skin-/hair-/nails-related; and other) and life impacts into six domains (psychological/emotional strain; cognitive impairment; dietary habit disruption; physical function decrements; interference with social relationships; and other). Eleven PRO instruments were considered to be promising for use in CKD; all had limitations. CONCLUSIONS: Although preliminary, the proposed conceptual model highlights key PROs for people with CKD and is intended to spur development of more tailored PRO instruments to assess these concepts.

Blood pressure and volume management in dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Blood pressure (BP) and volume control are critical components of dialysis care and have substantial impacts on patient symptoms, quality of life, and cardiovascular complications. Yet, developing consensus best practices for BP and volume control have been challenging, given the absence of objective measures of extracellular volume status and the lack of high-quality evidence for many therapeutic interventions. In February of 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference titled Blood Pressure and Volume Management in Dialysis to assess the current state of knowledge related to BP and volume management and identify opportunities to improve clinical and patient-reported outcomes among individuals receiving maintenance dialysis. Four major topics were addressed: BP measurement, BP targets, and pharmacologic management of suboptimal BP; dialysis prescriptions as they relate to BP and volume; extracellular volume assessment and management with a focus on technology-based solutions; and volume-related patient symptoms and experiences. The overarching theme resulting from presentations and discussions was that managing BP and volume in dialysis involves weighing multiple clinical factors and risk considerations as well as patient lifestyle and preferences, all within a narrow therapeutic window for avoiding acute or chronic volume-related complications. Striking this challenging balance requires individualizing the dialysis prescription by incorporating comorbid health conditions, treatment hemodynamic patterns, clinical judgment, and patient preferences into decision-making, all within local resource constraints.

Development of a person-centered interdisciplinary plan-of-care program for dialysis.

BACKGROUND: Dialysis care often focuses on outcomes that are of lesser importance to patients than to clinicians. There is growing international interest in individualizing care based on patient priorities, but evidence-based approaches are lacking. The objective of this study was to develop a person-centered dialysis care planning program. To achieve this objective we performed qualitative interviews, responsively developed a novel care planning program and then assessed program content and burden. METHODS: We conducted 25 concept elicitation interviews with US hemodialysis patients, care partners and care providers, using thematic analysis to analyze transcripts. Interview findings and interdisciplinary stakeholder panel input informed the development of a new care planning program, My Dialysis Plan. We then conducted 19 cognitive debriefing interviews with patients, care partners and care providers to assess the program's content and face validities, comprehensibility and burden. RESULTS: We identified five themes in concept elicitation interviews: feeling boxed in by the system, navigating dual lives, acknowledging an evolving identity, respecting the individual as a whole person and increasing individualization to enhance care. We then developed a person-centered care planning program and supporting materials that underwent 32 stakeholder-informed iterations. Data from subsequent cognitive interviews led to program revisions intended to improve contextualization and understanding, decrease burden and facilitate implementation. CONCLUSIONS: My Dialysis Plan is a content-valid, person-centered dialysis care planning program that aims to promote care individualization. Investigation of the program's capacity to improve patient experiences and outcomes is needed.

Comparative Cardiac Safety of Selective Serotonin Reuptake Inhibitors among Individuals Receiving Maintenance Hemodialysis.

BACKGROUND: Individuals receiving maintenance hemodialysis may be particularly susceptible to the lethal cardiac consequences of drug-induced QT prolongation because they have a substantial cardiovascular disease burden and high level of polypharmacy, as well as recurrent exposure to electrolyte shifts during dialysis. Electrophysiologic data indicate that among the selective serotonin reuptake inhibitors (SSRIs), citalopram and escitalopram prolong the QT interval to the greatest extent. However, the relative cardiac safety of SSRIs in the hemodialysis population is unknown. METHODS: In this retrospective cohort study, we used data from a cohort of Medicare beneficiaries receiving hemodialysis included in the US Renal Data System registry (2007-2014). We used a new-user design to compare the 1-year risk of sudden cardiac death among hemodialysis patients initiating SSRIs with a higher potential for prolonging the QT interval (citalopram, escitalopram) versus the risk among those initiating SSRIs with lower QT-prolonging potential (fluoxetine, fluvoxamine, paroxetine, sertraline). We estimated adjusted hazard ratios using inverse probability of treatment weighted survival models. Nonsudden cardiac death was treated as a competing event. RESULTS: The study included 30,932 (47.1%) hemodialysis patients who initiated SSRIs with higher QT-prolonging potential and 34,722 (52.9%) who initiated SSRIs with lower QT-prolonging potential. Initiation of an SSRI with higher versus lower QT-prolonging potential was associated with higher risk of sudden cardiac death (adjusted hazard ratio, 1.18; 95% confidence interval, 1.05 to 1.31). This association was more pronounced among elderly individuals, females, patients with conduction disorders, and those treated with other non-SSRI QT-prolonging medications. CONCLUSIONS: The heterogeneous QT-prolonging potential of SSRIs may differentially affect cardiac outcomes in the hemodialysis population.