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BACKGROUND: Most patients starting chronic in-center hemodialysis (HD) receive conventional hemodialysis (CHD) with three sessions per week targeting specific biochemical clearance. Observational studies suggest that patients with residual kidney function can safely be treated with incremental prescriptions of HD, starting with less frequent sessions and later adjusting to thrice-weekly HD. This trial aims to show objectively that clinically matched incremental HD (CMIHD) is non-inferior to CHD in eligible patients. METHODS: An unblinded, parallel-group, randomized controlled trial will be conducted across diverse healthcare systems and dialysis organizations in the USA. Adult patients initiating chronic hemodialysis (HD) at participating centers will be screened. Eligibility criteria include receipt of fewer than 18 treatments of HD and residual kidney function defined as kidney urea clearance ≥3.5 mL/min/1.73 m2 and urine output ≥500 mL/24 h. The 1:1 randomization, stratified by site and dialysis vascular access type, assigns patients to either CMIHD (intervention group) or CHD (control group). The CMIHD group will be treated with twice-weekly HD and adjuvant pharmacologic therapy (i.e., oral loop diuretics, sodium bicarbonate, and potassium binders). The CHD group will receive thrice-weekly HD according to usual care. Throughout the study, patients undergo timed urine collection and fill out questionnaires. CMIHD will progress to thrice-weekly HD based on clinical manifestations or changes in residual kidney function. Caregivers of enrolled patients are invited to complete semi-annual questionnaires. The primary outcome is a composite of patients' all-cause death, hospitalizations, or emergency department visits at 2 years. Secondary outcomes include patient- and caregiver-reported outcomes. We aim to enroll 350 patients, which provides ≥85% power to detect an incidence rate ratio (IRR) of 0.9 between CMIHD and CHD with an IRR non-inferiority of 1.20 (α = 0.025, one-tailed test, 20% dropout rate, average of 2.06 years of HD per patient participant), and 150 caregiver participants (of enrolled patients). DISCUSSION: Our proposal challenges the status quo of HD care delivery. Our overarching hypothesis posits that CMIHD is non-inferior to CHD. If successful, the results will positively impact one of the highest-burdened patient populations and their caregivers. TRIAL REGISTRATION: Clinicaltrials.gov NCT05828823. Registered on 25 April 2023.
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Estudos Multicêntricos como Assunto , Diálise Renal , Humanos , Resultado do Tratamento , Fatores de Tempo , Pesquisa Comparativa da Efetividade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos de Equivalência como Asunto , Estados Unidos , Falência Renal Crônica/terapia , Falência Renal Crônica/diagnósticoAssuntos
Ondansetron , Diálise Renal , Humanos , Ondansetron/farmacocinética , Ondansetron/uso terapêutico , Ondansetron/efeitos adversos , Antieméticos/farmacocinética , Antieméticos/efeitos adversos , Antieméticos/uso terapêutico , Falência Renal Crônica/terapia , Falência Renal Crônica/complicaçõesRESUMO
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 20â¯761 individuals receiving hemodialysis in 2019 (mean [SD] age, 74 [7] years; 51.1% male), 10â¯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.
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Diálise Renal , Humanos , Masculino , Estudos Transversais , Feminino , Idoso , Pessoa de Meia-Idade , Estados Unidos , Torsades de Pointes/induzido quimicamente , Síndrome do QT Longo/induzido quimicamente , Idoso de 80 Anos ou mais , Prescrições de Medicamentos/estatística & dados numéricos , Falência Renal Crônica/terapiaAssuntos
Morte Súbita Cardíaca , Ondansetron , Diálise Renal , Humanos , Diálise Renal/efeitos adversos , Morte Súbita Cardíaca/etiologia , Ondansetron/uso terapêutico , Ondansetron/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Antieméticos/efeitos adversos , Antieméticos/uso terapêutico , IdosoRESUMO
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.
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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.
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Nefropatias , Nefrologia , Diálise Renal , Humanos , Rim , Nefropatias/etiologia , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversosRESUMO
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.
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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.
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Poluição do Ar , Insuficiência Renal , Adulto , Humanos , Poluição do Ar/efeitos adversos , Albuminas , Biomarcadores , Estudos de Coortes , Ferritinas , Inflamação/induzido quimicamente , Material Particulado/efeitos adversos , Material Particulado/análise , Diálise Renal/efeitos adversos , Insuficiência Renal/induzido quimicamente , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Objective: Individuals receiving hemodialysis have high rates of sudden cardiac death (SCD). This study characterized oral atypical antipsychotic use and compared the cardiac safety of atypical antipsychotics with QT prolongation FDA warnings to that of atypical antipsychotics without such warnings among outpatients receiving hemodialysis. Methods: Data for this active-comparator, new-user cohort study were obtained from the U.S. Renal Data System (2007-2019). The primary outcome was 1-year SCD risk. Fine and Gray proportional subdistribution hazard models with inverse probability of treatment weighting were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: The quetiapine vs. atypical antipsychotic without QT prolongation warning cohort included 18,943 quetiapine new-users and 19,571 non-warning atypical antipsychotic new-users. When compared to new-use of atypical antipsychotics without QT prolongation warnings, quetiapine new-use was not associated with the risks of SCD (aHR (95% CI) = 1.00 (0.93, 1.07)) or broader cardiac outcomes. Comparisons of all atypical antipsychotics with QT prolongation warnings vs. atypical antipsychotics without warnings generated similar results. Conclusions: Quetiapine, which carries an FDA warning for QT prolongation, did not associate with cardiac risk compared to atypical antipsychotics without warnings among hemodialysis outpatients. Findings may inform prescriber selection of atypical antipsychotics in this population.
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Antipsicóticos , Morte Súbita Cardíaca , Fumarato de Quetiapina , Diálise Renal , Humanos , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Antipsicóticos/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Fumarato de Quetiapina/efeitos adversos , Idoso , Adulto , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Estados Unidos/epidemiologia , Estudos de CoortesRESUMO
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.
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Transplante de Rim , Crescimento Psicológico Pós-Traumático , Transtornos de Estresse Pós-Traumáticos , Adaptação Psicológica , Adulto , Criança , Humanos , Transplante de Rim/efeitos adversos , Qualidade de Vida/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologiaRESUMO
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.