Acute Kidney Injury Receiving Dialysis and Dialysis Care after Hospital Discharge.

The number of patients with AKI receiving outpatient hemodialysis (AKI-D) is increasing. At present, on the basis of limited data, approximately one third of patients with AKI-D who receive outpatient dialysis after hospital discharge survive and regain sufficient kidney function to discontinue dialysis. Data to inform dialysis management strategies that promote kidney function recovery and processes of care among patients with AKI-D receiving outpatient dialysis are lacking. In this article, we detail current trends in the incidence, risk factors, clinical outcomes, proposed management, and health policy landscape for patients with AKI-D receiving outpatient dialysis and identify areas for further research.

Comparative Effectiveness of Alternative Treatment Approaches to Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis: An Observational Trial Emulation.

RATIONALE & OBJECTIVE: Optimal approaches to treat secondary hyperparathyroidism (SHPT) in patients on maintenance hemodialysis (HD) have yet to be established in randomized controlled trials (RCTs). STUDY DESIGN: Two observational clinical trial emulations. SETTING & PARTICIPANTS: Both emulations included adults receiving in-center HD from a national dialysis organization. The patients who had SHPT in the period between 2009 and 2014, were insured for≥180 days by Medicare as primary payer, and did not have contraindications or poor health status limiting theoretical trial participation. EXPOSURE: The parathyroid hormone (PTH) Target Trial emulation included patients with new-onset SHPT (first PTH 300-600pg/mL), with 2 arms defined as up-titration of either vitamin D sterols or cinacalcet within 30 days (lower target) or no up-titration (higher target). The Agent Trial emulation included patients with a PTH≥300 pg/mL while on≥6µg weekly of vitamin D sterol (paricalcitol equivalent dose) and no prior history of cinacalcet. The 2 arms were defined by the first dose or agent change within 30 days (vitamin D-favoring [vitamin-D was up-titrated] vs cinacalcet-favoring [cinacalcet was added] vs nondefined [neither applies]). Multiple trials per patient were allowed in trial 2. OUTCOME: The primary outcome was all-cause death over 24 months; secondary outcomes included cardiovascular (CV) hospitalization or the composite of CV hospitalization or death. ANALYTICAL APPROACH: Pooled logistic regression. RESULTS: There were 1,152 patients in the PTH Target Trial (635 lower target and 517 higher target). There were 2,726 unique patients with 6,727 patient trials in the Agent Trial (6,268 vitamin D-favoring trials and 459 cinacalcet-favoring trials). The lower PTH target approach was associated with reduced adjusted hazard of death (HR, 0.71 [95% CI, 0.52-0.93]), CV hospitalization (HR, 0.78 [95% CI, 0.63-0.98]), and their composite (HR, 0.74 [95% CI, 0.61-0.89]). The cinacalcet-favoring approach demonstrated lower adjusted hazard of death compared to the vitamin D-favoring approach (HR, 0.79 [95% CI, 0.62-0.99]), but not of CV hospitalization or the composite outcome. LIMITATIONS: Potential for residual confounding; low use of cinacalcet with low power. CONCLUSIONS: SHPT management that is focused on lower PTH targets may lower mortality and CV disease in patients receiving HD. These findings should be confirmed in a pragmatic randomized trial. PLAIN-LANGUAGE SUMMARY: Optimal approaches to treat secondary hyperparathyroidism (SHPT) have not been established in randomized controlled trials. Data from a national dialysis organization was used to identify patients with SHPT in whom escalated treatment may be indicated. The approach to treatment was defined based on observed upward titration of SHPT-controlling medications: earlier titration (lower target) versus delayed titration (higher target); and the choice of medication (cinacalcet vs vitamin D sterols). In the first trial emulation, we estimated a 29% lower rate of death and 26% lower rate of cardiovascular disease or death for patients managed with a lower versus higher target approach. Cinacalcet versus vitamin D-favoring approaches were not consistently associated with outcomes in the second trial emulation. This observational study suggests the need for additional clinical trials of SHPT treatment intensity.

Designing an Implementable Clinical Prediction Model for Near-Term Mortality and Long-Term Survival in Patients on Maintenance Hemodialysis.

RATIONALE & OBJECTIVE: The life expectancy of patients treated with maintenance hemodialysis (MHD) is heterogeneous. Knowledge of life-expectancy may focus care decisions on near-term versus long-term goals. The current tools are limited and focus on near-term mortality. Here, we develop and assess potential utility for predicting near-term mortality and long-term survival on MHD. STUDY DESIGN: Predictive modeling study. SETTING & PARTICIPANTS: 42,351 patients contributing 997,381 patient months over 11 years, abstracted from the electronic health record (EHR) system of midsize, nonprofit dialysis providers. NEW PREDICTORS & ESTABLISHED PREDICTORS: Demographics, laboratory results, vital signs, and service utilization data available within dialysis EHR. OUTCOME: For each patient month, we ascertained death within the next 6 months (ie, near-term mortality) and survival over more than 5 years during receipt of MHD or after kidney transplantation (ie, long-term survival). ANALYTICAL APPROACH: We used least absolute shrinkage and selection operator logistic regression and gradient-boosting machines to predict each outcome. We compared these to time-to-event models spanning both time horizons. We explored the performance of decision rules at different cut points. RESULTS: All models achieved an area under the receiver operator characteristic curve of≥0.80 and optimal calibration metrics in the test set. The long-term survival models had significantly better performance than the near-term mortality models. The time-to-event models performed similarly to binary models. Applying different cut points spanning from the 1st to 90th percentile of the predictions, a positive predictive value (PPV) of 54% could be achieved for near-term mortality, but with poor sensitivity of 6%. A PPV of 71% could be achieved for long-term survival with a sensitivity of 67%. LIMITATIONS: The retrospective models would need to be prospectively validated before they could be appropriately used as clinical decision aids. CONCLUSIONS: A model built with readily available clinical variables to support easy implementation can predict clinically important life expectancy thresholds and shows promise as a clinical decision support tool for patients on MHD. Predicting long-term survival has better decision rule performance than predicting near-term mortality. PLAIN-LANGUAGE SUMMARY: Clinical prediction models (CPMs) are not widely used for patients undergoing maintenance hemodialysis (MHD). Although a variety of CPMs have been reported in the literature, many of these were not well-designed to be easily implementable. We consider the performance of an implementable CPM for both near-term mortality and long-term survival for patients undergoing MHD. Both near-term and long-term models have similar predictive performance, but the long-term models have greater clinical utility. We further consider how the differential performance of predicting over different time horizons may be used to impact clinical decision making. Although predictive modeling is not regularly used for MHD patients, such tools may help promote individualized care planning and foster shared decision making.

Peritoneal Dialysis Technique Survival: A Cohort Study.

RATIONALE & OBJECTIVE: Reasons for transfer from peritoneal dialysis (PD) to hemodialysis (HD) remain incompletely understood. Among incident and prevalent patients receiving PD, we evaluated the association of clinical factors, including prior treatment with HD, with PD technique survival. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults who initiated PD at a Dialysis Clinic, Inc (DCI) outpatient facility between January 1, 2010, and September 30, 2019. EXPOSURE: The primary exposure of interest was timing of PD start, categorized as PD-first, PD-early, or PD-late. Other covariates included demographics, clinical characteristics, and routine laboratory results. OUTCOME: Modality switch from PD to HD sustained for more than 90 days. ANALYTICAL APPROACH: Multivariable Fine-Gray models with competing risks and time-varying covariates, stratified at 9 months to account for lack of proportionality. RESULTS: Among 5,224 patients who initiated PD at a DCI facility, 3,174 initiated dialysis with PD ("PD-first"), 942 transitioned from HD to PD within 90 days ("PD-early"), and 1,108 transitioned beyond 90 days ("PD-late"); 1,472 (28%) subsequently transferred from PD to HD. The PD-early and PD-late patients had a higher risk of transfer to HD as compared with PD-first patients (in the first 9 months: adjusted hazard ratio [AHR], 1.51 [95% CI, 1.17-1.96] and 2.41 [95% CI, 1.94-3.00], respectively; and after 9 months: AHR, 1.16 [95% CI, 0.99-1.35] and AHR, 1.43 [95% CI, 1.24-1.65], respectively). More peritonitis episodes, fewer home visits, lower serum albumin levels, lower residual kidney function, and lower peritoneal clearance calculated with weekly Kt/V were additional risk factors for PD-to-HD transfer. LIMITATIONS: Missing data on dialysis adequacy and residual kidney function, confounded by short PD technique survival. CONCLUSIONS: Initiating dialysis with PD is associated with greater PD technique survival, though many of those who initiate PD-late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower Kt/V are risk factors for PD-to-HD transfer that may be amenable to intervention. PLAIN-LANGUAGE SUMMARY: Peritoneal dialysis (PD) is an important kidney replacement modality with several potential advantages compared with in-center hemodialysis (HD). However, a substantial number of patients transfer to in-center HD early on, without having experienced the quality-of-life and other benefits that come with sustained maintenance of PD. Using retrospective data from a midsize national dialysis provider, we found that initiating dialysis with PD is associated with longer maintenance of PD, compared with initiating dialysis with HD and a later switch to PD. However, many of those who initiate PD-late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower small protein removal are other risk factors for PD-to-HD transfer that may be amenable to intervention.

Effectiveness of an Intervention to Improve Decision Making for Older Patients With Advanced Chronic Kidney Disease : A Randomized Controlled Trial.

BACKGROUND: Older patients with advanced chronic kidney disease (CKD) face difficult decisions about managing kidney failure, frequently experiencing decisional conflict, regret, and treatment misaligned with preferences. OBJECTIVE: To assess whether a decision aid about kidney replacement therapy improved decisional quality compared with usual care. DESIGN: Multicenter, randomized, controlled trial. (ClinicalTrials.gov: NCT03522740). SETTING: 8 outpatient nephrology clinics associated with 4 U.S. centers. PARTICIPANTS: English-fluent patients, 70 years and older with nondialysis CKD stages 4 to 5 recruited from 2018 to 2020. INTERVENTION: DART (Decision-Aid for Renal Therapy) is an interactive, web-based decision aid for older adults with CKD. Both groups received written education about treatments. MEASUREMENTS: Change in the decisional conflict scale (DCS) score from baseline to 3, 6, 12, and 18 months. Secondary outcomes included change in prognostic and treatment knowledge and change in uncertainty. RESULTS: Among 400 participants, 363 were randomly assigned: 180 to usual care, 183 to DART. Decisional quality improved with DART with mean DCS declining compared with control (mean difference, -8.5 [95% CI, -12.0 to -5.0]; P < 0.001), with similar findings at 6 months, attenuating thereafter. At 3 months, knowledge improved with DART versus usual care (mean difference, 7.2 [CI, 3.7 to 10.7]; P < 0.001); similar findings at 6 months were modestly attenuated at 18 months (mean difference, 5.9 [CI, 1.4 to 10.3]; P = 0.010). Treatment preferences changed from 58% "unsure" at baseline to 28%, 20%, 23%, and 14% at 3, 6, 12, and 18 months, respectively, with DART, versus 51% to 38%, 35%, 32%, and 18% with usual care. LIMITATION: Latinx patients were underrepresented. CONCLUSION: DART improved decision quality and clarified treatment preferences among older adults with advanced CKD for 6 months after the DART intervention. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute (PCORI).

Optimal Care for Kidney Health: Development of a Merit-based Incentive Payment System (MIPS) Value Pathway.

The Merit-based Incentive Payment System (MIPS) is a mandatory pay-for-performance program through the Centers for Medicare & Medicaid Services (CMS) that aims to incentivize high-quality care, promote continuous improvement, facilitate electronic exchange of information, and lower health care costs. Previous research has highlighted several limitations of the MIPS program in assessing nephrology care delivery, including administrative complexity, limited relevance to nephrology care, and inability to compare performance across nephrology practices, emphasizing the need for a more valid and meaningful quality assessment program. This article details the iterative consensus-building process used by the American Society of Nephrology Quality Committee from May 2020 to July 2022 to develop the Optimal Care for Kidney Health MIPS Value Pathway (MVP). Two rounds of ranked-choice voting among Quality Committee members were used to select among nine quality metrics, 43 improvement activities, and three cost measures considered for inclusion in the MVP. Measure selection was iteratively refined in collaboration with the CMS MVP Development Team, and new MIPS measures were submitted through CMS's Measures Under Consideration process. The Optimal Care for Kidney Health MVP was published in the 2023 Medicare Physician Fee Schedule Final Rule and includes measures related to angiotensin-converting enzyme inhibitor and angiotensin receptor blocker use, hypertension control, readmissions, acute kidney injury requiring dialysis, and advance care planning. The nephrology MVP aims to streamline measure selection in MIPS and serves as a case study of collaborative policymaking between a subspecialty professional organization and national regulatory agencies.

Cardiovascular Effects of Home Dialysis Therapies: A Scientific Statement From the American Heart Association.

Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage kidney disease. Currently, thrice-weekly in-center hemodialysis for 3 to 5 hours per session is the most common therapy worldwide for patients with treated kidney failure. Outcomes with thrice-weekly in-center hemodialysis are poor. Emerging evidence supports the overarching hypothesis that a more physiological approach to administering dialysis therapy, including in the home through home hemodialysis or peritoneal dialysis, may lead to improvement in several cardiovascular risk factors and cardiovascular outcomes compared with thrice-weekly in-center hemodialysis. The Advancing American Kidney Health Initiative, which has a goal of increasing the use of home dialysis, is aligned with the American Heart Association's 2024 mission to champion a full and healthy life and health equity. We conclude that incorporation of interdisciplinary care models to increase the use of home dialysis therapies in an equitable manner will contribute to the ultimate goal of improving outcomes for patients with kidney failure and cardiovascular disease.

Home dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams.

SARS-CoV-2 Vaccine Effectiveness and Breakthrough Infections Among Patients Receiving Maintenance Dialysis.

RATIONALE & OBJECTIVE: SARS-CoV-2 vaccine effectiveness and immunogenicity threshold associated with protection against COVID-19-related hospitalization or death in the dialysis population are unknown. STUDY DESIGN: Retrospective, observational study. SETTING & PARTICIPANTS: Adult patients without COVID-19 history receiving maintenance dialysis through a national dialysis provider and treated between February 1 and December 18, 2021, with follow-up through January 17, 2022. PREDICTOR: SARS-CoV-2 vaccination status. OUTCOMES: All SARS-CoV-2 infections, composite of hospitalization or death following COVID-19. ANALYTICAL APPROACH: Logistic regression was used to determine COVID-19 case rates and vaccine effectiveness. RESULTS: Of 16,213 patients receiving dialysis during the study period, 12,278 (76%) were fully vaccinated, 589 (4%) were partially vaccinated, and 3,346 (21%) were unvaccinated by the end of follow-up. Of 1,225 COVID-19 cases identified, 550 (45%) occurred in unvaccinated patients, and 891 (73%) occurred during the Delta variant-dominant period. Between the pre-Delta period and the Delta-dominant period, vaccine effectiveness rates against a severe COVID-19-related event (hospitalization or death) were 84% and 70%, respectively. In the subset of 3,202 vaccinated patients with at least one anti-spike immunoglobulin G (IgG) assessment, lower anti-spike IgG levels were associated with higher case rates per 10,000 days and higher adjusted hazard ratios for infection and COVID-19-related hospitalization or death. LIMITATIONS: Observational design, residual biases, and confounding may exist. CONCLUSIONS: Among maintenance dialysis patients, SARS-CoV-2 vaccination was associated with a lower risk of COVID-19 diagnosis and associated hospitalization or death. Among vaccinated patients, a low anti-spike IgG level is associated with worse COVID-19-related outcomes.

Effect of Long-term Exercise Training on Physical Performance and Cardiorespiratory Function in Adults With CKD: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: The safety and efficacy of long-term exercise training in reducing physical functional loss in older adults with advanced CKD and comorbidity is uncertain. STUDY DESIGN: Multicenter, parallel group, randomized controlled trial. SETTINGS & PARTICIPANTS: Adults 55 years and older with estimated glomerular filtration rate (eGFR) of 15 to <45 mL/min/1.73 m2 enrolled from centers in Baltimore and Boston. INTERVENTION: Twelve months of in-center supervised exercise training incorporating majority aerobic but also muscle strengthening activities or a group health education control intervention, randomly assigned in 1:1 ratio. OUTCOME: Primary outcomes were cardiorespiratory fitness and submaximal gait at 6 and 12 months quantified by peak oxygen consumption (Vo2peak) on graded exercise treadmill test and distance walked on the 6-minute walk test, respectively. Secondary outcomes were changes in lower extremity function, eGFR, albuminuria, glycemia, blood pressure, and body mass index. RESULTS: Among 99 participants, the mean age was 68 years, 62% were African American, and the mean eGFR was 33 mL/min/1.73 m2; 59% had diabetes, and 29% had coronary artery disease. Among those randomized to exercise, 59% of exercise sessions were attended in the initial 6 months. Exercise was well tolerated without excess occurrence of adverse events. At 6 months, aerobic capacity was higher among exercise participants (17.9 ± 5.5 vs 15.9 ± 7.0 mL/kg/min, P = 0.03), but the differences were not sustained at 12 months. The 6-minute walk distance improved more in the exercise group (adjusted difference: 98 feet [P = 0.02; P = 0.03 for treatment-by-time interaction]). The exercise group had greater improvements on the Timed Up and Go Test (P = 0.04) but not the Short Physical Performance Battery (P = 0.8). LIMITATIONS: Planned sample size was not reached. Loss to follow-up and dropout were greater than anticipated. CONCLUSIONS: Among adults aged ≥55 years with CKD stages 3b-4 and a high level of medical comorbidity, a 12-month program of in-center aerobic and resistance exercise training was safe and associated with improvements in physical functioning. FUNDING: Government grants (National Institutes of Health). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01462097.

Development and Validation of the Rating of CKD Knowledge Among Older Adults (Know-CKD) With Kidney Failure.

RATIONALE & OBJECTIVE: Few older adults with kidney failure engage in shared decision making (SDM) for kidney replacement therapy. The lack of instruments to assess SDM-relevant knowledge domains may contribute to this. We assessed the reliability and validity of a new instrument, the Rating of CKD Knowledge Older Adults (Know-CKD). STUDY DESIGN: Multistage process, including a stakeholder-engaged development phase, pilot testing, and validation of a knowledge instrument using a cross-sectional survey of older adults with CKD. SETTING & PARTICIPANTS: 363 patients aged 70+years with nondialysis advanced chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR]<30mL/min/1.73m2) in Boston, Chicago, Portland, ME, and San Diego from June 2018 and January 2020. EXPOSURE: Educational level, higher literacy (Single Item Literacy Screener [SILS]) and numeracy (Subjective Numeracy Scale [SNS]), having participated in clinic-sponsored dialysis education, and self-reported "feeling informed" about options for treatment. OUTCOME: Validity and reliability of the Know-CKD instrument. ANALYTICAL APPROACH: Reliability was assessed with the Kuder-Richardson-20 coefficient. Construct validity was demonstrated by testing a priori hypotheses using t test, analysis of variance (ANOVA) tests, and linear regression analyses. RESULTS: The mean (± SD) participant age was 77.6±5.9 years, and mean eGFR was 22.7±7.2mL/min/1.73m2; 281 participants (78%) self-reported as White. The 12-item Know-CKD assessment had good reliability (Kuder-Richardson-20 reliability coefficient=0.75), and a mean score of 58.2% ± 22.3 SD. The subscales did not attain acceptable reliability. The proportion answering correctly on each item ranged from 20.1% to 91.7%. In examining construct validity, the hypothesized associations held; Know-CKD significantly associated with higher education (ß=6.98 [95% CI, 1.34-12.61], P=0.02), health literacy (ß = -12.67 [95% CI, -19.49 to-5.86], P≤0.001), numeracy per 10% higher (ß=1.85 [95% CI, 1.02-2.69], P≤0.001), and attendance at dialysis class (ß=18.28 [95% CI, 13.30-23.27], P≤0.001). These associations were also observed for the subscales except for prognosis (not associated with literacy or numeracy). LIMITATIONS: Know-CKD is only available in English and has been used only in research settings. CONCLUSIONS: For older adults facing dialysis initiation decisions, Know-CKD is a valid, reliable, and easy to administer measure of knowledge. Further research should examine the relationship of kidney disease knowledge and SDM, patient satisfaction, and clinical outcomes. PLAIN-LANGUAGE SUMMARY: The Rating of CKD Knowledge Among Older Adults (Know-CKD) study measures knowledge of chronic kidney disease (CKD) and is designed for older adults. Most existing knowledge measures for CKD focus on people of all ages and all CKD stages. This measure is useful because it will allow researchers to assess how well patient education efforts are working. Patient education is a way to help patients make decisions about their care. We describe how the measure was developed by a team of doctors, researchers, and patients, and how the measure performed among persons with advanced CKD aged 70 years and older. Know-CKD can inform efforts to improve shared decision-making research and practice for older patients with kidney disease.

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.

Difelikefalin improves itch-related sleep disruption in patients undergoing haemodialysis.

BACKGROUND: Poor sleep quality is associated with increased mortality and lower quality of life in patients with chronic kidney disease-associated pruritus (CKD-aP). Difelikefalin reduces itch in patients with CKD-aP undergoing haemodialysis. This post hoc analysis of Phase 3 studies (3105 and the pooled dataset from KALM-1 and KALM-2) evaluated whether itch reduction in CKD-aP improved sleep quality. METHODS: Itch intensity was assessed in patients undergoing haemodialysis, who had moderate-to-severe CKD-aP treated with intravenous difelikefalin (0.5 µg/kg, three times weekly) (N = 222, Study 3105; N = 426, KALM-1/-2) or placebo (N = 425, KALM-1/-2) for 12 weeks, using the Worst Itch Intensity Numerical Rating Scale (WI-NRS). Sleep quality was assessed using the sleep disability question of the 5-D itch scale (5­D SDQ) in all studies and, in Study 3105, with the Sleep Quality Numeric Rating Scale (SQ-NRS). RESULTS: Greater improvements in sleep quality were observed in patients with ≥ 3-point, versus < 3-point WI-NRS improvement using SQ-NRS in Study 3105 (mean [95% confidence interval]: -5.2 [-5.6, -4.8] vs -1.5 [-2.0, -1.0]) and 5-D SDQ in KALM-1/-2 (-1.8 [-2.1, -1.6] vs -0.8 [-1.1, -0.4]). SQ-NRS and WI-NRS scores correlated strongly at baseline and Week 12 in Study 3105 (Spearman correlation coefficient: 0.77 and 0.84, respectively). Correlations were also observed between 5-D SDQ and WI-NRS scores in Study 3105 and KALM­1/­2. CONCLUSIONS: In patients undergoing haemodialysis with moderate-to-severe CKD-aP, itch reduction with intravenous difelikefalin was associated with improved sleep quality. As disturbed sleep may contribute to mortality and morbidity in CKD-aP, difelikefalin may help to address a major clinical burden by improving sleep quality, secondary to itch relief.

Mobility in Older Adults Receiving Maintenance Hemodialysis: A Qualitative Study.

RATIONALE & OBJECTIVE: For older adults, maintaining mobility is a major priority, especially for those with advanced chronic diseases like kidney failure. However, our understanding of the factors affecting mobility in older adults receiving maintenance hemodialysis is limited. STUDY DESIGN: Descriptive qualitative study. SETTING & PARTICIPANTS: Using purposive sampling, we recruited (1) persons aged≥60 years receiving maintenance hemodialysis; and (2) care partners (≥18 years) providing regular support to an older adult receiving hemodialysis. During a single in-person home visit, we assessed mobility using the Short Physical Performance Battery (SPPB) and conducted individual one-on-one interviews regarding important personal factors related to mobility. ANALYTICAL APPROACH: Descriptive statistics were used for demographic and SPPB data. Transcripts underwent thematic coding, informed by the International Classification of Function framework of mobility. We used conceptual content analysis to inductively extract themes and subthemes. RESULTS: We enrolled 31 older adults receiving hemodialysis (42% female, 68% Black) with a mean age of 73±8 years and mean dialysis vintage of 4.6±3.5 years; their mean SPPB score was 3.6±2.8 points. Among 12 care partners (75% female, 33% Black), the mean age was 54±16 years and mean SPPB score was 10.1±2.4 points. Major themes extracted were (1) mobility represents independence; (2) mobility is precarious; (3) limitations in mobility cause distress; (4) sources of encouragement and motivation are critical; and (5) adaptability is key. LIMITATIONS: Modest sample from single geographic area. CONCLUSIONS: For older adults receiving hemodialysis, mobility is severely limited and is often precarious in nature, causing distress. Older adults receiving hemodialysis and their care partners have identified sources of encouragement and motivation for mobility, and cite an adaptable mindset as important. Future studies should conceptualize mobility as a variable condition and build on this outlook of adaptability in the development of interventions.

Clinical Trial Considerations in Developing Treatments for Early Stages of Common, Chronic Kidney Diseases: A Scientific Workshop Cosponsored by the National Kidney Foundation and the US Food and Drug Administration.

In the past decade, advances in the validation of surrogate end points for chronic kidney disease (CKD) progression have heightened interest in evaluating therapies in early CKD. In December 2020, the National Kidney Foundation sponsored a scientific workshop in collaboration with the US Food and Drug Administration (FDA) to explore patient, provider, and payor perceptions of the value of treating early CKD. The workshop reviewed challenges for trials in early CKD, including trial designs, identification of high-risk populations, and cost-benefit and safety considerations. Over 90 people representing a range of stakeholders including experts in clinical trials, nephrology, cardiology and endocrinology, patient advocacy organizations, patients, payors, health economists, regulators and policy makers attended a virtual meeting. There was consensus among the attendees that there is value to preventing the development and treating the progression of early CKD in people who are at high risk for progression, and that surrogate end points should be used to establish efficacy. Attendees also concluded that cost analyses should be holistic and include aspects beyond direct savings for treatment of kidney failure; and that safety data should be collected outside/beyond the duration of a clinical trial. Successful drug development and implementation of effective therapies will require collaboration across sponsors, patients, patient advocacy organizations, medical community, regulators, and payors.

Shared Decision Making Among Older Adults With Advanced CKD.

RATIONALE & OBJECTIVE: Older adults with advanced chronic kidney disease (CKD) face difficult decisions about dialysis initiation. Although shared decision making (SDM) can help align patient preferences and values with treatment options, the extent to which older patients with CKD experience SDM remains unknown. STUDY DESIGN: A cross-sectional analysis of patient surveys examining decisional readiness, treatment options education, care partner support, and SDM. SETTING & PARTICIPANTS: Adults aged 70 years or older from Boston, Chicago, San Diego, or Portland (Maine) with nondialysis advanced CKD. PREDICTORS: Decisional readiness factors, treatment options education, and care partner support. OUTCOMES: Primary: SDM measured by the 9-item Shared Decision Making Questionnaire (SDM-Q-9) instrument, with higher scores reflecting greater SDM. Exploratory: Factors associated with SDM. ANALYTICAL APPROACH: We used multivariable linear regression models to examine the associations between SDM and predictors, controlling for demographic and health factors. RESULTS: Among 350 participants, mean age was 78 ± 6 years, 58% were male, 13% identified as Black, and 48% had diabetes. Mean SDM-Q-9 score was 52 ± 28. SDM item agreement ranged from 41% of participants agreeing that "my doctor and I selected a treatment option together" to 73% agreeing that "my doctor told me that there are different options for treating my medical condition." In multivariable analysis adjusted for demographic characteristics, lower estimated glomerular filtration rate, and diabetes, being "well informed" and "very well informed" about kidney treatment options, having higher decisional certainty, and attendance at a kidney treatment options class were independently associated with higher SDM-Q-9 scores. LIMITATIONS: The cross-sectional study design limits the ability to make temporal associations between SDM and the predictors. CONCLUSIONS: Many older patients with CKD do not experience SDM when making dialysis decisions, emphasizing the need for greater access to and delivery of education for individuals with advanced CKD.

Seroresponse to Inactivated and Recombinant Influenza Vaccines Among Maintenance Hemodialysis Patients.

RATIONALE & OBJECTIVE: High-dose influenza vaccine provides better protection against influenza infection in older adults than standard-dose vaccine. We compared vaccine seroresponse among hemodialysis patients over a period of 4 months after administration of high-dose trivalent inactivated (HD-IIV3), standard-dose quadrivalent inactivated (SD-IIV4), or quadrivalent recombinant quadrivalent (RIV4) influenza vaccine. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: Patients at 4 hemodialysis clinics who received influenza vaccine. EXPOSURE: Type of influenza vaccine. OUTCOME: Hemagglutination inhibition (HI) titers were measured at baseline and at 1, 2, 3, and 4 months after vaccination. The primary outcome was seroprotection rates at HI titers of at least 1:40 and at least 1:160 (antibody levels providing protection from infection in approximately 50% and 95% of immunocompetent individuals, respectively) at 1, 2, 3, and 4 months after vaccination. ANALYTICAL APPROACH: We calculated geometric mean titer as well as seroprotection and seroconversion rates. Adjusted generalized linear models with additional trend analyses were performed to evaluate the association between vaccine type and outcomes. RESULTS: 254 hemodialysis patients were vaccinated against influenza with HD-IIV3 (n = 141), SD-IIV4 (n = 36), or RIV4 (n = 77). A robust initial seroresponse to influenza A strains was observed after all 3 vaccines. Geometric mean titer and seroprotection (HI titer ≥1:160) rates against influenza A strains were higher and more sustained with HD-IIV3 than SD-IIV4 or RIV4. More than 80% of patients vaccinated with HD-IIV3 were seroprotected (HI titer ≥1:160) at month 4 (P < 0.001), whereas, among patients vaccinated with SD-IIV4 or RIV4, seroprotection rates were similar to those at baseline. Seroprotection rates were lower against B strains for all vaccines. LIMITATIONS: Because of the use of observational data, bias from unmeasured confounders may exist. Some age subgroups were small in number. Clinical outcome data were not available. CONCLUSIONS: Hemodialysis patients exhibited high seroprotection rates after all 3 influenza vaccines. The seroresponse waned more slowly with HD-IIV3 compared with SD-IIV4 and RIV4 vaccines.

Kidney Recovery and Death in Critically Ill Patients With COVID-19-Associated Acute Kidney Injury Treated With Dialysis: The STOP-COVID Cohort Study.

RATIONALE & OBJECTIVE: Acute kidney injury treated with kidney replacement therapy (AKI-KRT) occurs frequently in critically ill patients with coronavirus disease 2019 (COVID-19). We examined the clinical factors that determine kidney recovery in this population. STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 4,221 adults not receiving KRT who were admitted to intensive care units at 68 US hospitals with COVID-19 from March 1 to June 22, 2020 (the "ICU cohort"). Among these, 876 developed AKI-KRT after admission to the ICU (the "AKI-KRT subcohort"). EXPOSURE: The ICU cohort was analyzed using AKI severity as the exposure. For the AKI-KRT subcohort, exposures included demographics, comorbidities, initial mode of KRT, and markers of illness severity at the time of KRT initiation. OUTCOME: The outcome for the ICU cohort was estimated glomerular filtration rate (eGFR) at hospital discharge. A 3-level outcome (death, kidney nonrecovery, and kidney recovery at discharge) was analyzed for the AKI-KRT subcohort. ANALYTICAL APPROACH: The ICU cohort was characterized using descriptive analyses. The AKI-KRT subcohort was characterized with both descriptive analyses and multinomial logistic regression to assess factors associated with kidney nonrecovery while accounting for death. RESULTS: Among a total of 4,221 patients in the ICU cohort, 2,361 (56%) developed AKI, including 876 (21%) who received KRT. More severe AKI was associated with higher mortality. Among survivors, more severe AKI was associated with an increased rate of kidney nonrecovery and lower kidney function at discharge. Among the 876 patients with AKI-KRT, 588 (67%) died, 95 (11%) had kidney nonrecovery, and 193 (22%) had kidney recovery by the time of discharge. The odds of kidney nonrecovery was greater for lower baseline eGFR, with ORs of 2.09 (95% CI, 1.09-4.04), 4.27 (95% CI, 1.99-9.17), and 8.69 (95% CI, 3.07-24.55) for baseline eGFR 31-60, 16-30, ≤15 mL/min/1.73 m2, respectively, compared with eGFR > 60 mL/min/1.73 m2. Oliguria at the time of KRT initiation was also associated with nonrecovery (ORs of 2.10 [95% CI, 1.14-3.88] and 4.02 [95% CI, 1.72-9.39] for patients with 50-499 and <50 mL/d of urine, respectively, compared to ≥500 mL/d of urine). LIMITATIONS: Later recovery events may not have been captured due to lack of postdischarge follow-up. CONCLUSIONS: Lower baseline eGFR and reduced urine output at the time of KRT initiation are each strongly and independently associated with kidney nonrecovery among critically ill patients with COVID-19.

End-stage renal disease and metalworking fluid exposure.

OBJECTIVE: Despite increasing prevalence of end-stage renal disease (ESRD), little attention has been directed to how occupational exposures may contribute to risk. Our objective was to investigate the relationship between metalworking fluids (MWF) and ESRD in a cohort of 36 703 male autoworkers. METHODS: We accounted for competing risk of death, using the subdistribution hazard approach to estimate subhazard ratios (sHRs) and 95% CIs in models with cubic splines for cumulative exposure to MWF (straight, soluble or synthetic). RESULTS: Based on 501 ESRD cases and 13 434 deaths, we did not observe an association between MWF and ESRD overall. We observed modest associations between MWF and ESRD classification of glomerulonephritis and diabetic nephropathy. For glomerulonephritis, the 60th percentile of straight MWF was associated with an 18% increased subhazard (sHR=1.18, 95% CI: 0.99 to 1.41). For diabetic nephropathy, the subhazard increased 28% at the 60th percentile of soluble MWF (sHR=1.28, 95% CI: 1.00 to 1.64). Differences by race suggest that black males may have higher disease rates following MWF exposure. CONCLUSIONS: Exposure to straight and soluble MWF may be related to ESRD classification, though this relationship should be further examined.

Immunogenicity of SARS-CoV-2 Vaccine in Dialysis.

BACKGROUND: Patients receiving maintenance dialysis represent a high-risk, immune-compromised population with 15%-25% COVID-19 mortality rate who were unrepresented in clinical trials of mRNA vaccines. METHODS: All patients receiving maintenance dialysis who received two doses of SARS-CoV-2 mRNA vaccines with antibody test results drawn ≥14 days after the second dose, as documented in the electronic health record through March 18, 2021, were included. Response was on the basis of levels of Ig-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike-antigen (seropositive ≥2 U/L) using an FDA-approved semiquantitative chemiluminescent assay (ADVIA Centaur XP/XPT COV2G). RESULTS: Among 186 patients on dialysis from 30 clinics in eight states tested 23±8 days after receiving two vaccine doses, there were 165 (88.7%) responders with 70% at maximum titer. There was no significant difference between BNT162b2/Pfizer (148 out of 168, 88.1%) and mRNA-1273/Moderna (17 out of 18, 94.4%), P=0.42. All 38 patients with COVID-19 history were responders, with 97% at maximum titer. Among patients without COVID-19, 127 out of 148 (85.8%) were responders, comparable between BNT162b2/Pfizer (113 out of 133) and mRNA-1273/Moderna (14 out of 15) vaccines (85.0% versus 93.3%, P=0.38). CONCLUSIONS: Most patients receiving maintenance dialysis responded after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine, suggesting the short-term development of antispike antibody is good, giving hope that most of these patients who are vulnerable, once immunized, will be protected from COVID-19. Longer-term evaluation is needed to determine antibody titer durability and if booster dose(s) are warranted. Further research to evaluate the approach to patients without a serologic response is needed, including benefits of additional dose(s) or administration of alternate options.