From Home to Wearable Hemodialysis: Barriers, Progress, and Opportunities.

Although the past two decades have seen substantial proportional growth of home hemodialysis in the United States, the absolute number of patients treated with home hemodialysis remains small. Currently available stationary hemodialysis devices for use in the home have inherent limitations that represent barriers for more widespread adoption by a larger proportion of individuals with kidney failure. These limitations include device weight and bulk, ergonomics considerations, technical complexity, vascular access challenges, and limited remote patient monitoring. Recent years have witnessed a resurgence in research and development of prototype wearable kidney replacement devices incorporating innovations in miniaturization, new biomaterials, and new methods for toxin clearance and dialysate regeneration. Recent work has built on five decades of incremental innovation in wearable dialysis concepts and prototypes, starting from the work by Kolff in the 1970s. Wearable dialysis devices that successfully overcome key persistent barriers to successful development and adoption of these technologies will radically reshape the landscape of kidney replacement therapies and have the potential to dramatically improve the lives of individuals living with kidney failure.

Evaluation and Measurement Properties of a Patient-Reported Experience Measure for Home Dialysis.

BACKGROUND: No previously validated patient-reported experience measures exist for use among patients undergoing home dialysis. We tested the Home Dialysis Care Experience survey, a newly developed 26-item experience measure, among patients from 30 dialysis facilities in the United States. METHODS: Using mail and telephone survey modalities, we approached 1372 patients treated with peritoneal dialysis or home hemodialysis for participation. Using the results from completed surveys, we evaluated item calibration by assessing item floor and ceiling effects. We tested three sets of composite scores and used factor analysis to assess model fit for each. We evaluated associations of composite scores with global ratings and separately with patient and dialysis facility characteristics. Finally, we measured test-retest reliability in patients who completed the survey at two separate time points. RESULTS: Overall, 495 eligible patients completed at least one survey (response rate 36%). Of these, 49 completed the survey in Spanish and 61 completed a second survey within 30 days. We did not detect significant floor or ceiling effects, except for one item that demonstrated >90% responses at the top response option. Analyses supported one 12-item composite scale with high internal consistency reliability: Quality of Home Dialysis Care and Operations (Cronbach alpha=0.85). This scale strongly correlated with overall staff rating ( r =0.73) and overall center rating ( r =0.70). Patient demographic and dialysis facility characteristics were not consistently associated with composite scale scores or overall staff or center ratings. Intraclass correlation coefficients in the test-retest population were 0.74 for the Quality scale, 0.88 for overall staff rating, and 0.90 for overall center rating. CONCLUSIONS: The Home Dialysis Care Experience survey is a 26-item measure that includes one composite scale and two global rating scores and is an informative tool to evaluate patient experience of care for home dialysis.

Gout Prevalence, Practice Patterns, and Associations with Outcomes in North American Dialysis Patients.

INTRODUCTION: Gout occurs frequently in patients with kidney disease and can lead to a significant burden on quality of life. Gout prevalence, and its association with outcomes in hemodialysis (HD) and peritoneal dialysis (PD) populations located in North America, is unknown. METHODS: We used data from North America cohorts of 70,297 HD patients (DOPPS, 2012-2020) and 5117 PD patients (PDOPPS, 2014-2020). We used three definitions of gout for this analysis: (1) having an active prescription for colchicine or febuxostat; (2) having an active prescription for colchicine, febuxostat, or allopurinol; or (3) having an active prescription for colchicine, febuxostat, or allopurinol, or prior diagnosis of gout. Propensity score matching was used to compare outcomes among patients with versus without gout. Outcomes included erythropoietin resistance index (ERI=erythropoiesis stimulating agent dose per week/(hemoglobin×weight)), all-cause mortality, hospitalization, and patient-reported outcomes (PROs). RESULTS: The gout prevalence was 13% in HD and 21% in PD; it was highest among incident dialysis patients. Description of previous history of gout was rare, and identification of gout defined by colchicine (2%-3%) or febuxostat (1%) prescription was less frequent than by allopurinol (9%-12%). Both HD and PD patients with gout (versus no gout) were older, were more likely male, had higher body mass index, and had higher prevalence of cardiovascular comorbidities. About half of patients with a gout history were prescribed urate-lowering therapy. After propensity score matching, mean ERI was 3%-6% higher for gout versus non-gout patients while there was minimal evidence of association with clinical outcomes or PROs. CONCLUSION: In a large cohort of PD and HD patients in North America, we found that gout occurs frequently and is likely under-reported. Gout was not associated with adverse clinical or PROs.

Comparative Effectiveness of Dialysis Modality on Laboratory Parameters of Mineral Metabolism.

INTRODUCTION: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are prevalent in patients undergoing maintenance dialysis. Yet, there are limited and mixed evidence on the effects of different dialysis modalities involving longer treatment times or higher frequencies on CKD-MBD markers. METHODS: This cohort study used data from 132,523 incident dialysis patients treated with any of the following modalities: conventional thrice-weekly in-center hemodialysis, nocturnal in-center hemodialysis (NICHD), home hemodialysis (HHD), or peritoneal dialysis (PD) from 2007 to 2011. We used marginal structural models fitted with inverse probability weights to adjust for fixed and time-varying confounding and informative censoring. We estimated the average effects of treatments with different dialysis modalities on time-varying serum concentrations of CKD-MBD markers: albumin-corrected calcium, phosphate, parathyroid hormone (PTH), and alkaline phosphatase (ALP) using pooled linear regression. RESULTS: Most of the cohort were exclusively treated with conventional in-center hemodialysis, while few were ever treated with NICHD or HHD. At the baseline, PD patients had the lowest mean and median values of PTH, while NICHD patients had the highest median values. During follow-up, compared to hemodialysis patients, patients treated with NICHD had lower mean serum PTH (19.8 pg/mL [95% confidence interval: 2.8, 36.8] lower), whereas PD and HHD patients had higher mean PTH (39.7 pg/mL [31.6, 47.8] and 51.2 pg/mL [33.0, 69.3] higher, respectively). Compared to hemodialysis patients, phosphate levels were lower for patients treated with NICHD (0.44 mg/dL [0.37, 0.52] lower), PD (0.15 mg/dL [0.12, 0.19] lower), or HHD (0.33 mg/dL [0.27, 0.40] lower). There were no clinically meaningful associations between dialysis modalities and concentrations of calcium or ALP. CONCLUSION: In incident dialysis patients, compared to treatment with conventional in-center hemodialysis, treatments with other dialysis modalities with longer treatment times or higher frequency were associated with different patterns of serum phosphate and PTH. Given the recent growth in the use of dialysis modalities other than hemodialysis, the associations between the treatment and the CKD-MBD markers warrant additional study.

Patient-reported outcomes in hemodialysis vascular access: A call to action.

While access-related dysfunction is a clear driver of clinical outcomes and costs, the full impact of vascular access dysfunction on patient experience and quality of life is not fully characterized in the literature. One way to more comprehensively characterize the patient experience from the patient perspective is through patient reported outcomes (PROs). However, the limited implementation of PROs in clinical trials, patient registries, quality measurement, and other research settings has significantly constrained the patient voice in evaluation of vascular access outcomes and vascular access decision-making. To address these issues, the Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and the U.S. Food and Drug Administration, assembled an interdisciplinary workgroup to enhance uptake of access-related PROs with the aims of: (1) reviewing the domains of HRQOL that are affected by vascular access, collect information on existing instruments that measure access-specific HRQOL in hemodialysis, and identify gaps in existing measures; (2) identifying and critically assessing barriers to widespread use of access-specific PRO measures; and (3) defining initiatives to overcome barriers and make recommendations for strategies to improve the use and utility of access-specific PRO measures. A consensus group process identified potential barriers to use of PRO measures in six categories: (1) PRO misperceptions, (2) patient factors, (3) regulators and payers, (4) instrument factors, (5) study design, and (6) physicians. The workgroup provided recommendations for actions to promote the widespread utilization of vascular access-related PRO measures in five categories: (1) development of vascular access-specific PRO measures, (2) ensuring comprehensive assessment when using vascular access PRO measures, (3) ensuring accessibility and applicability of vascular access PRO measures to all end stage kidney disease populations, (4) establishing universal guidelines and accepted vascular access PRO measures, and (5) engaging stakeholders across all facets.

Development and Content Validity of a Patient-Reported Experience Measure for Home Dialysis.

BACKGROUND AND OBJECTIVES: The population of patients with kidney failure in the United States using home dialysis modalities is growing rapidly. Unlike for in-center hemodialysis, there is no patient-reported experience measure for assessment of patient experience of care for peritoneal dialysis or home hemodialysis. We sought to develop and establish content validity of a patient-reported experience measure for patients undergoing home dialysis using a mixed methods multiple stakeholder approach. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a structured literature review, followed by concept elicitation focus groups and interviews among 65 participants, including 21 patients on home dialysis, 33 home dialysis nurses, three patient care partners, and eight nephrologists. We generated a list of candidate items for possible measure inclusion and conducted a national prioritization exercise among 91 patients on home dialysis and 39 providers using a web-based platform. We drafted the Home Dialysis Care Experience instrument and conducted cognitive debriefing interviews to evaluate item interpretability, order, and structure. We iteratively refined the measure on the basis of interview findings. RESULTS: The literature review and concept elicitation phases supported 15 domains of home dialysis care experience in six areas: communication and education of patients, concern and helpfulness of the care team, proficiency of the care team, patient-centered care, care coordination, and amenities and environment. Focus groups results showed that domains of highest importance for measure inclusion were patient education and communication, care coordination, and personalization of care. Prioritization exercise results confirmed focus group findings. Cognitive debriefing indicated that the final measure was easily understood and supported content validity. CONCLUSIONS: The Home Dialysis Care Experience instrument is a 26-item patient-reported experience measure for use in peritoneal dialysis and home hemodialysis. The Home Dialysis Care Experience instrument represents the first rigorously developed and content-valid English-language instrument for assessment of patient-reported experience of care in home dialysis.

Microvascular Benefits of New Antidiabetic Agents: A Systematic Review and Network Meta-Analysis of Kidney Outcomes.

CONTEXT: Diabetic kidney disease affects nearly one-third of US adults with prevalent type 2 diabetes mellitus (T2DM). The use of new antidiabetic medications in the prevention and treatment of diabetic kidney disease is a growing area of research interest. OBJECTIVE: We sought to characterize the risk of developing a composite kidney outcome among patients receiving a new antidiabetic medication of the SGLT-2i, GLP-1ra, and DPP-4i drug classes. METHODS: We conducted a systematic literature search in MEDLINE to identify randomized trials observing kidney safety endpoints associated with the use of new antidiabetic medications. Two independent reviewers selected the 7 eligible studies for analysis. Included studies were published between January 2013 and March 2020, conducted with adult participantss, published full-text in English, and observed composite kidney outcomes. A network meta-analysis was conducted within a Bayesian framework using a fixed-effects model with uninformative priors. RESULTS: A qualitative assessment of transitivity was conducted to ensure similar distribution of potential modifiers across studies. Included studies were generally comparable in mean age, glycated hemoglobin A1c (HbA1c), and mean duration of T2DM at baseline. MAIN CONCLUSIONS: Compared with placebo, dapagliflozin was associated with the greatest reduction in risk of developing the composite kidney outcome (hazard ratio 0.53; 95% credible interval, 0.43-0.66) followed by empagliflozin, canagliflozin, semaglutide, and liraglutide. Linagliptin did not show a significant reduction in risk of the outcome. LIMITATIONS: This analysis was limited by the scarcity of data for kidney safety endpoints in large, randomized clinical trials. Although the heterogeneity statistic was low, there are slight differences in study design and baseline demographic characteristics across trials.

KDOQI US Commentary on the 2020 ISPD Practice Recommendations for Prescribing High-Quality Goal-Directed Peritoneal Dialysis.

The recently published 2020 International Society for Peritoneal Dialysis (ISPD) practice recommendations regarding prescription of high-quality goal-directed peritoneal dialysis differ fundamentally from previous guidelines that focused on "adequacy" of dialysis. The new ISPD publication emphasizes the need for a person-centered approach with shared decision making between the individual performing peritoneal dialysis and the clinical care team while taking a broader view of the various issues faced by that individual. Cognizant of the lack of strong evidence for the recommendations made, they are labeled as "practice points" rather than being graded numerically. This commentary presents the views of a work group convened by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) to assess these recommendations and assist clinical providers in the United States in interpreting and implementing them. This will require changes to the current clinical paradigm, including greater resource allocation to allow for enhanced services that provide a more holistic and person-centered assessment of the quality of dialysis delivered.

Vascular access-specific health-related quality of life impacts among hemodialysis patients: qualitative development of the hemodialysis access-related quality of life (HARQ) instrument.

BACKGROUND: End stage kidney disease and hemodialysis dependence are associated with impairments in health-related quality of life (HRQOL), which may be related to vascular access (VA). Few HRQOL measures are VA-specific and none differentiate HRQOL impact by VA type. We developed a VA-targeted HRQOL measure to distinguish the impact of fistulas, grafts and catheters. METHODS: We created an initial item pool based on literature review and then conducted focus groups at 4 US sites with 37 adults and interviews with nine dialysis clinicians about VA's impact on HRQOL. We then drafted the Hemodialysis Access-Related Quality of Life (HARQ) measure and cognitively tested it with 17 hemodialysis patients. Focus group and cognitive interview participants were diverse in age, gender, years on dialysis, and VA. RESULTS: We identified six domains for the HARQ: symptoms, physical functioning, emotional impacts, social and role functioning, sleep, and care-related burdens. Cognitive interviews indicated that items were easily understood and supported content validity. Attributing HRQOL impact to VA as opposed to other hemodialysis burden was challenging for some items. Some items were dropped that were considered redundant by patients, limitations while dressing was added, and reference to VA-specific impact was included for each item. The average Flesch-Kincaid reading grade level for the revised 47-item HARQ was 5.3. CONCLUSIONS: The HARQ features VA-specific content not addressed in other HRQOL measures, making it ideal for comparisons of different VA types and new VA technologies. The psychometric properties of the HARQ will be evaluated in future research.

Symptom Prioritization among Adults Receiving In-Center Hemodialysis: A Mixed Methods Study.

BACKGROUND AND OBJECTIVES: Individuals receiving in-center hemodialysis experience a high symptom burden that detrimentally affects their quality of life. There are few evidence-based interventions for symptom relief in this population. To stimulate innovation in symptom management, data on patient symptom prioritization and treatment preferences are needed. We undertook this study to (1) identify patient-prioritized symptoms for the development of symptom relief therapies and (2) elicit preferences for treatments among individuals receiving hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a mixed methods study that included focus groups in Carrboro, North Carolina; Tucson, Arizona; and Seattle, Washington and a nationally distributed online survey. Focus group transcripts were analyzed for patterns, and the highest priority symptoms were determined on the basis of frequency and report severity. We used focus group findings to inform survey items. Focus group and survey results were crossvalidated and synthesized for final symptom prioritization. RESULTS: There were 32 participants across three focus groups and 87 survey respondents from 27 states in the United States. The physical symptoms of insomnia, fatigue, muscle cramping, and nausea/vomiting and the mood symptoms of anxiety and depressed mood were reported by participants in all focus groups. Among survey respondents, fatigue (94%), cramping (79%), and body aches (76%) were the most common physical symptoms, and feeling depressed (66%), worried (64%), and frustrated (63%) were the most common mood symptoms. The top-prioritized symptoms were consistent across focus group and survey participants and included the physical symptoms insomnia, fatigue, and cramping and the mood symptoms anxiety, depression, and frustration. Participants indicated that symptom frequency, duration, unpredictability, and social and financial effects factored most heavily into symptom prioritization. CONCLUSIONS: Patients prioritized the physical symptoms of insomnia, fatigue, and cramping and the mood symptoms of anxiety, depression, and frustration as the top symptoms for which to find new therapies.

Weekly Standard Kt/Vurea and Clinical Outcomes in Home and In-Center Hemodialysis.

BACKGROUND AND OBJECTIVES: Patients undergoing hemodialysis with a frequency other than thrice weekly are not included in current clinical performance metrics for dialysis adequacy. The weekly standard Kt/Vurea incorporates treatment frequency, but there are limited data on its association with clinical outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used multivariable regression to examine the association of dialysis standard Kt/Vurea with BP and metabolic control (serum potassium, calcium, bicarbonate, and phosphorus) in patients incidental to dialysis treated with home (n=2373) or in-center hemodialysis (n=109,273). We further used Cox survival models to examine the association of dialysis standard Kt/Vurea with mortality, hospitalization, and among patients on home hemodialysis, transfer to in-center hemodialysis. RESULTS: After adjustment for potential confounders, patients with dialysis standard Kt/Vurea <2.1 had higher BPs compared with patients with standard Kt/Vurea 2.1 to <2.3 (3.4 mm Hg higher [P<0.001] for home hemodialysis and 0.9 mm Hg higher [P<0.001] for in-center hemodialysis). There were no clinically meaningful associations between dialysis standard Kt/Vurea and markers of metabolic control, irrespective of dialysis modality. There was no association between dialysis standard Kt/Vurea and risk for mortality, hospitalization, or transfer to in-center hemodialysis among patients undergoing home hemodialysis. Among patients on in-center hemodialysis, dialysis standard Kt/Vurea <2.1 was associated with higher risk (adjusted hazard ratio, 1.11; 95% confidence interval, 1.07 to 1.14) and standard Kt/Vurea ≥2.3 was associated with lower risk (adjusted hazard ratio, 0.97; 95% confidence interval, 0.94 to 0.99) for death compared with standard Kt/Vurea 2.1 to <2.3. Additional analyses limited to patients with available data on residual kidney function showed similar relationships of dialysis and total (dialysis plus kidney) standard Kt/Vurea with outcomes. CONCLUSIONS: Current targets for standard Kt/Vurea have limited utility in identifying individuals at increased risk for adverse clinical outcomes for those undergoing home hemodialysis but may enhance risk stratification for in-center hemodialysis.