Prescription and Dispensation of QT-Prolonging Medications in Individuals Receiving Hemodialysis.

Importance: Individuals with dialysis-dependent kidney failure have numerous risk factors for medication-related adverse events, including receipt of care by multiple clinicians and initiation of some QT-prolonging medications with known risk of torsades de pointes (TdP), which is associated with higher risk of sudden cardiac death. Little is known about the prescription and dispensation patterns of QT-prolonging medications among people receiving dialysis, hindering efforts to reduce drug-related harm from these and other medications in this high-risk population. Objective: To examine prescription and dispensation patterns of QT-prolonging medications with known TdP risk and selected interacting medications prescribed to individuals receiving hemodialysis. Design, Setting, and Participants: This cross-sectional study included patients 60 years or older who were enrolled in Medicare Parts A, B, and D receiving in-center hemodialysis from January 1 to December 31, 2019. Analyses were conducted from October 20, 2022, to June 16, 2023. Exposures: New-user prescriptions for the 7 most frequently filled QT-prolonging medications characterized by the timing of the new prescription relative to acute care encounters, the type of prescribing clinician and pharmacy that dispensed the medication, and concomitant use of selected medications known to interact with the 7 most frequently filled QT-prolonging medications with known TdP risk. Main Outcomes and Measures: The main outcomes were the frequencies of the most commonly filled and new-use episodes of QT-prolonging medications; the timing of medication fills relative to acute care events; prescribers and dispensing pharmacy characteristics for new use of medications; and the frequency and types of new-use episodes with concurrent use of potentially interacting medications. Results: Of 20 761 individuals receiving hemodialysis in 2019 (mean [SD] age, 74 [7] years; 51.1% male), 10 992 (52.9%) filled a study drug prescription. Approximately 80% (from 78.6% for odansetron to 93.9% for escitalopram) of study drug new-use prescriptions occurred outside of an acute care event. Between 36.8% and 61.0% of individual prescriptions originated from general medicine clinicians. Between 16.4% and 26.2% of these prescriptions occurred with the use of another QT-prolonging medication. Most potentially interacting drugs were prescribed by different clinicians (46.3%-65.5%). Conclusions and Relevance: In this cross-sectional study, QT-prolonging medications for individuals with dialysis-dependent kidney failure were commonly prescribed by nonnephrology clinicians and from nonacute settings. Prescriptions for potentially interacting medications often originated from different prescribers. Strategies aimed at minimizing high-risk medication-prescribing practices in the population undergoing dialysis are needed.

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.

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.

QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis.

Rationale & Objective: Treatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassium shifts, may augment the proarrhythmic effects of these medications. The primary objective of this study was to examine whether the serum-to-dialysate gradient modifies the cardiac safety of azithromycin, and separately, levofloxacin/moxifloxacin. Study Design: Retrospective observational cohort study using a new-user study design. Setting & Population: Adult in-center hemodialysis patients with Medicare coverage in the US Renal Data System (2007-2017). Exposure: Initiation of azithromycin (or levofloxacin/moxifloxacin) as compared to amoxicillin-based antibiotics (exposure). Serum-to-dialysate potassium gradient (effect modifier). Individual patients could contribute multiple study antibiotic treatment episodes to the analyses. Outcomes: Sudden cardiac death (14 days). Analytical Approach: Inverse probability of treatment-weighted survival models to estimate HRs and robust 95% CIs. Results: The azithromycin versus amoxicillin-based antibiotic cohort included 89,379 unique patients with 113,516 azithromycin and 103,493 amoxicillin-based treatment episodes. Azithromycin versus amoxicillin-based antibiotic treatment was associated with a higher risk of sudden cardiac death overall, HR, 1.68; 95% CI, 1.31-2.16. The risk was numerically higher when the baseline serum-to-dialysate potassium gradient was ≥3 mEq/L compared with <3 mEq/L (HR, 2.22; 95% CI, 1.46-3.40 vs HR, 1.43; 95% CI. 1.04-1.96, P interaction = 0.07). Analogous analyses in a respiratory fluoroquinolone (levofloxacin/moxifloxacin) versus amoxicillin-based antibiotic cohort with 79,449 unique patients and 65,959 respiratory fluoroquinolone and 103,776 amoxicillin-based treatment episodes yielded similar results. Limitations: Residual confounding. Conclusions: Although treatment with azithromycin and, separately, respiratory fluoroquinolones were each associated with a heightened risk of sudden cardiac death, this risk was augmented in the setting of larger serum-to-dialysate potassium gradients. Minimizing the potassium gradient may be an approach to reduce the cardiac risk of these antibiotics.

Associations of Air Pollution and Serum Biomarker Abnormalities in Individuals with Hemodialysis-Dependent Kidney Failure.

BACKGROUND: Ambient particles with a median aerodynamic diameter of <2.5 µm (PM2.5) is a ubiquitous air pollutant with established adverse health consequences. While postulated to promote a systemic inflammatory response, limited studies have demonstrated changes in serum biomarkers related to PM2.5 exposure. We aim to examine associations between short-term PM2.5 exposure and commonly measured biomarkers known to be affected by inflammation among patients receiving maintenance in-center hemodialysis. METHODS: We conducted a retrospective open cohort study from January 1, 2008, to December 31, 2014. Adult hemodialysis patients were identified from the United States Renal Data System and linked at the patient level to laboratory data from a large dialysis organization. Daily ambient PM2.5 was estimated on a 1-km grid and assigned to cohort patients based on the ZIP codes of dialysis clinics. Serum albumin, serum ferritin, transferrin saturation (TSAT), and serum hemoglobin were ascertained from the dialysis provider organization database. Mixed-effect models were used to assess the changes in biomarker levels associated with PM2.5 exposure. RESULTS: The final cohort included 173,697 hemodialysis patients. Overall, the daily ZIP-level ambient PM2.5 averages were 8.4-8.5 µg/m3. A 10-µg/m3 increase in same-day ambient PM2.5 exposure was associated with higher relative risks of lower albumin (relative risk [RR], 1.01; 95% confidence interval [95% CI], 1.01 to 1.02) and lower hemoglobin (RR, 1.02; 95% CI, 1.01 to 1.03). Associations of same-day ambient PM2.5 exposure and higher ferritin and lower TSAT did not reach statistical significance. CONCLUSIONS: Short-term PM2.5 exposure was associated with lower serum hemoglobin and albumin among patients receiving in-center hemodialysis. These findings lend support to the role of inflammation in PM2.5 exposure-outcome associations.

Efficacy, Safety, and Tolerability of Oral Furosemide Among Patients Receiving Hemodialysis: A Pilot Study.

Introduction: Diuretic use may reduce volume-related complications in hemodialysis. We evaluated the efficacy, safety, and tolerability of furosemide in patients with hemodialysis-dependent kidney failure. Methods: We conducted an open label, single-arm, 18-week, dose titration pilot study of oral furosemide (maximum dose 320 mg/day) among patients receiving maintenance hemodialysis who reported at least 1 cup of urine output per day. The primary efficacy outcome was an increase from baseline to a specified threshold of 24-hour urine volume, with the threshold based on baseline urine volume (<200 ml/day vs. ≥200 ml/day). Safety outcomes included hypokalemia and hypomagnesemia, and tolerability was assessed by prespecified patient-reported symptoms. Results: Of the 39 participants, 28 (72%) received the expected furosemide dose, 3 (8%) underwent dose reduction, 5 (12%) discontinued furosemide without dose reduction, and 3 (8%) underwent dose reduction and subsequently discontinued furosemide. The median (quartile 1, quartile 3) baseline 24-hour urine volume was 290 ml (110, 740), and the maximum, average daily study furosemide dose ranged from 69 mg/day to 320 mg/d. The urine output efficacy outcome was met by 12 (33%), 11 (33%), and 7 (22%) participants at weeks 5, 12, and 18, respectively, in the intention-to-treat analysis, and by 12 (39%), 9 (35%), and 7 (28%) participants at weeks 5, 12, and 18, respectively, in the on-treatment analysis. There were no electrolyte, furosemide level, or patient-reported hearing change safety events. Conclusion: Furosemide was generally safe and well tolerated, but only one-third of participants met the efficacy definition at week 5. The clinical importance of the efficacy findings is uncertain.

Post-Traumatic Stress Disorder and Post-Traumatic Growth following Kidney Transplantation.

Background: Kidney transplantation (KT) is a life-saving therapy for kidney failure. However, KT recipients can suffer from debilitating depression, post-traumatic stress disorder (PTSD), and suicide. In contrast to PTSD, post-traumatic growth (PTG) is a positive psychologic change in response to a challenging situation. PTG has been studied in other chronic diseases, but less is known about its role in the setting of KT. We sought to elucidate the prevalence, predictors, and the effect of PTSD and PTG on post-KT outcomes. We also considered the roles of benefit finding and resilience. Methods: In a literature review, we identified publications that examined PTSD, PTG, benefit finding, and/or resilience in KT recipients. We excluded case reports and first-person narratives. Publications meeting the specified criteria after full text review underwent data abstraction and descriptive analysis. Results: Of the 1013 unique citations identified, 39 publications met our criteria. PTSD was the most common construct evaluated (16 publications). Resilience was studied in 11 publications, PTG in nine, and benefit finding in five. Up to 21% of adult and 42% of pediatric KT recipients may experience PTSD, which is associated with lower quality of life (QOL), impaired sleep, and other psychiatric comorbidity. PTG was associated with improved QOL, kidney function, and reduced risk of organ rejection. Although benefit finding tended to increase post KT, resilience remained stable post KT. Like PTG, resilience was associated with lower psychologic distress and increased treatment adherence and confidence in the health care team. Conclusions: PTG, resilience, and benefit finding appear to reduce the risk of PTSD, promote well-being, and reduce risk of graft failure in KT recipients. Future research to understand these relationships better will allow clinicians and researchers to develop interventions to promote PTG, resilience, and benefit finding, and potentially improve post-transplant outcomes such as adherence and reducing risk of organ rejection.

Development of a Patient Preference Survey for Wearable Kidney Replacement Therapy Devices.

Background: Recent innovations have the potential to disrupt the current paradigm for kidney failure treatment. The US Food and Drug Administration is committed to incorporating valid scientific evidence about how patients weigh the benefits and risks of new devices into their decision making, but to date, premarket submission of patient preference information (PPI) has been limited for kidney devices. With input from stakeholders, we developed a survey intended to yield valid PPI, capturing how patients trade off the potential benefits and risks of wearable dialysis devices and in-center hemodialysis. Methods: We conducted concept elicitation interviews with individuals receiving dialysis to inform instrument content. After instrument drafting, we conducted two rounds of pretest interviews to evaluate survey face validity, comprehensibility, and perceived relevance. We pilot tested the survey with in-center hemodialysis patients to assess comprehensibility and usability further. Throughout, we used participant input to guide survey refinements. Results: Thirty-six individuals receiving in-center or home dialysis participated in concept elicitation (N=20) and pretest (N=16) interviews. Participants identified reduced fatigue, lower treatment burden, and enhanced freedom as important benefits of a wearable device, and many expressed concerns about risks related to device disconnection-specifically bleeding and infection. We drafted a survey that included descriptions of the risks of serious bleeding and serious infection and an assessment of respondent willingness to wait for a safer device. Input from pretest interviewees led to various instrument modifications, including treatment descriptions, item wording, and risk-level explanations. Pilot testing of the updated survey among 24 in-center hemodialysis patients demonstrated acceptable survey comprehensibility and usability, although 50% of patients required some assistance. Conclusions: The final survey is a 54-item web-based instrument that will yield estimates of the maximal acceptable risk for the described wearable device and willingness to wait for wearable devices with lower risk.

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.