Enhancing the Cardiovascular Safety of Hemodialysis Care Using Multimodal Provider Education and Patient Activation Interventions: Protocol for a Cluster Randomized Controlled Trial.

BACKGROUND: End-stage kidney disease (ESKD) is treated with dialysis or kidney transplantation, with most patients with ESKD receiving in-center hemodialysis treatment. This life-saving treatment can result in cardiovascular and hemodynamic instability, with the most common form being low blood pressure during the dialysis treatment (intradialytic hypotension [IDH]). IDH is a complication of hemodialysis that can involve symptoms such as fatigue, nausea, cramping, and loss of consciousness. IDH increases risks of cardiovascular disease and ultimately hospitalizations and mortality. Provider-level and patient-level decisions influence the occurrence of IDH; thus, IDH may be preventable in routine hemodialysis care. OBJECTIVE: This study aims to evaluate the independent and comparative effectiveness of 2 interventions-one directed at hemodialysis providers and another for patients-in reducing the rate of IDH at hemodialysis facilities. In addition, the study will assess the effects of interventions on secondary patient-centered clinical outcomes and examine factors associated with a successful implementation of the interventions. METHODS: This study is a pragmatic, cluster randomized trial to be conducted in 20 hemodialysis facilities in the United States. Hemodialysis facilities will be randomized using a 2 × 2 factorial design, such that 5 sites will receive a multimodal provider education intervention, 5 sites will receive a patient activation intervention, 5 sites will receive both interventions, and 5 sites will receive none of the 2 interventions. The multimodal provider education intervention involved theory-informed team training and the use of a digital, tablet-based checklist to heighten attention to patient clinical factors associated with increased IDH risk. The patient activation intervention involves tablet-based, theory-informed patient education and peer mentoring. Patient outcomes will be monitored during a 12-week baseline period, followed by a 24-week intervention period and a 12-week postintervention follow-up period. The primary outcome of the study is the proportion of treatments with IDH, which will be aggregated at the facility level. Secondary outcomes include patient symptoms, fluid adherence, hemodialysis adherence, quality of life, hospitalizations, and mortality. RESULTS: This study is funded by the Patient-Centered Outcomes Research Institute and approved by the University of Michigan Medical School's institutional review board. The study began enrolling patients in January 2023. Initial feasibility data will be available in May 2023. Data collection will conclude in November 2024. CONCLUSIONS: The effects of provider and patient education on reducing the proportion of sessions with IDH and improving other patient-centered clinical outcomes will be evaluated, and the findings will be used to inform further improvements in patient care. Improving the stability of hemodialysis sessions is a critical concern for clinicians and patients with ESKD; the interventions targeted to providers and patients are predicted to lead to improvements in patient health and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT03171545; https://clinicaltrials.gov/ct2/show/NCT03171545. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46187.

Assessing the impact of transitional care units on dialysis patient outcomes: A multicenter, propensity score-matched analysis.

INTRODUCTION: Inadequate predialysis care and education impacts the selection of a dialysis modality and is associated with adverse clinical outcomes. Transitional care units (TCUs) aim to meet the unmet educational needs of incident dialysis patients, but their impact beyond increasing home dialysis utilization has been incompletely characterized. METHODS: This retrospective study included adults initiating in-center hemodialysis at a TCU, matched to controls (1:4) with no TCU history initiating in-center hemodialysis. Patients were followed for up to 14 months. TCUs are dedicated spaces where staff provide personalized education and as-needed adjustments to dialysis prescriptions. For many patients, therapy was initiated with four to five weekly dialysis sessions, with at least some sessions delivered by home dialysis machines. Outcomes included survival, first hospitalization, transplant waiting-list status, post-TCU dialysis modality, and vascular access type. FINDINGS: The study included 724 patients initiating dialysis across 48 TCUs, with 2892 well-matched controls. At the end of 14 months, patients initiating dialysis in a TCU were significantly more likely to be referred and/or wait-listed for a kidney transplant than controls (57% vs. 42%; p < 0.0001). Initiation of dialysis at a TCU was also associated with significantly lower rates of receiving in-center hemodialysis at 14 months (74% vs. 90%; p < 0.0001) and higher rates of arteriovenous access (70% vs. 63%; p = 0.003). Although not statistically significant, TCU patients were more likely to survive and less likely to be hospitalized during follow-up than controls. DISCUSSION: Although TCUs are sometimes viewed as only a means for enhancing utilization of home dialysis, patients attending TCUs exhibited more favorable outcomes across all endpoints. In addition to being 2.5-fold more likely to receive home dialysis, TCU patients were 42% more likely to be referred for transplantation. Our results support expanding utilization of TCUs for patients with inadequate predialysis support.

The CALCIPHYX study: a randomized, double-blind, placebo-controlled, Phase 3 clinical trial of SNF472 for the treatment of calciphylaxis.

BACKGROUND: Calcific uraemic arteriolopathy (CUA; calciphylaxis) is a rare disease seen predominantly in patients receiving dialysis. Calciphylaxis is characterized by poorly healing or non-healing wounds, and is associated with mortality, substantial morbidity related to infection and typically severe pain. In an open-label Phase 2 clinical trial, SNF472, a selective inhibitor of vascular calcification, was well-tolerated and associated with improvement in wound healing, reduction of wound-related pain and improvement in wound-related quality of life (QoL). Those results informed the design of the CALCIPHYX trial, an ongoing, randomized, placebo-controlled, Phase 3 trial of SNF472 for treatment of calciphylaxis. METHODS: In CALCIPHYX, 66 patients receiving haemodialysis who have an ulcerated calciphylaxis lesion will be randomized 1:1 to double-blind SNF472 (7 mg/kg intravenously) or placebo three times weekly for 12 weeks (Part 1), then receive open-label SNF472 for 12 weeks (Part 2). All patients will receive stable background care, which may include pain medications and sodium thiosulphate, in accordance with the clinical practices of each site. A statistically significant difference between the SNF472 and placebo groups for improvement of either primary endpoint at Week 12 will demonstrate efficacy of SNF472: change in Bates-Jensen Wound Assessment Tool-CUA (a quantitative wound assessment tool for evaluating calciphylaxis lesions) or change in pain visual analogue scale score. Additional endpoints will address wound-related QoL, qualitative changes in wounds, wound size, analgesic use and safety. CONCLUSIONS: This randomized, placebo-controlled Phase 3 clinical trial will examine the efficacy and safety of SNF472 in patients who have ulcerated calciphylaxis lesions. Patient recruitment is ongoing.

Challenges and Opportunities in Expanding Home Hemodialysis for 2025.

The Advancing American Kidney Health Initiative has set an aggressive target for home dialysis growth in the United States, and expanding both peritoneal dialysis and home hemodialysis (HHD) will be required. While there has been a growth in HHD across the United States in the last decade, its value in controlling specific risk factors has been underappreciated and as such its appropriate utilization has lagged. Repositioning how nephrologists incorporate HHD as a critical renal replacement therapy will require overcoming a number of barriers. Advancing education of both nephrology trainees and nephrologists in practice, along with increasing patient and family education on the benefits and requirements for HHD, is essential. Implementation of a transitional care unit design coupled with an intensive patient curriculum will increase patient awareness and comfort for HHD; patients on peritoneal dialysis reaching a modality transition point will benefit from Experience the Difference programs acclimating them to HHD. In addition, the potential link between HHD program size and patient outcomes will necessitate an increase in the size of the average HHD program to more consistently deliver quality dialysis results. Addressing the implications of the nursing shortage and need for designing in scope staffing models are necessary to safeguard HHD growth. Seemingly, certain government payment policy changes and physician documentation requirements deserve further examination. Future HHD innovations must result in decreasing the burden of care for HHD patients, optimize the level of device and biometric data flow, facilitate a more functional centralized patient management care approach, and leverage computerized clinical decision support for modality assignment.

SARS-CoV-2 in Spent Dialysate from Chronic Peritoneal Dialysis Patients with COVID-19.

Background: To date, it is unclear whether SARS-CoV-2 is present in spent dialysate from patients with COVID-19 on peritoneal dialysis (PD). Our aim was to assess the presence or absence of SARS-CoV-2 in spent dialysate from patients on chronic PD who had a confirmed diagnosis of COVID-19. Methods: Spent PD dialysate samples from patients on PD who were positive for COVID-19 were collected between March and August 2020. The multiplexed, real-time RT-PCR assay contained primer/probe sets specific to different SARS-CoV-2 genomic regions and to bacteriophage MS2 as an internal process control for nucleic acid extraction. Demographic and clinical data were obtained from patients' electronic health records. Results: A total of 26 spent PD dialysate samples were collected from 11 patients from ten dialysis centers. Spent PD dialysate samples were collected, on average, 25±13 days (median, 20; range, 10-45) after the onset of symptoms. The temporal distance of PD effluent collection relative to the closest positive nasal-swab RT-PCR result was 15±11 days (median, 14; range, 1-41). All 26 PD effluent samples tested negative at three SARS-CoV-2 genomic regions. Conclusions: Our findings indicate the absence of SARS-CoV-2 in spent PD dialysate collected at ≥10 days after the onset of COVID-19 symptoms. We cannot rule out the presence of SARS-CoV-2 in spent PD dialysate in the early stage of COVID-19.

Remote Treatment Monitoring on Hospitalization and Technique Failure Rates in Peritoneal Dialysis Patients.

Background: An integrated kidney disease healthcare company implemented a peritoneal dialysis (PD) remote treatment monitoring (RTM) application in 2016. We assessed if RTM utilization associates with hospitalization and technique failure rates. Methods: We used data from adult (age ≥18 years) patients on PD treated from October 2016 through May 2019 who registered online for the RTM. Patients were classified by RTM use during a 30-day baseline after registration. Groups were: nonusers (never entered data), moderate users (entered one to 15 treatments), and frequent users (entered >15 treatments). We compared hospital admission/day and sustained technique failure (required >6 consecutive weeks of hemodialysis) rates over 3, 6, 9, and 12 months of follow-up using Poisson and Cox models adjusted for patient/clinical characteristics. Results: Among 6343 patients, 65% were nonusers, 11% were moderate users, and 25% were frequent users. Incidence rate of hospital admission was 22% (incidence rate ratio [IRR]=0.78; P=0.002), 24% (IRR=0.76; P<0.001), 23% (IRR=0.77; P≤0.001), and 26% (IRR=0.74; P≤0.001) lower in frequent users after 3, 6, 9, and 12 months, respectively, versus nonusers. Incidence rate of hospital days was 38% (IRR=0.62; P=0.013), 35% (IRR=0.65; P=0.001), 34% (IRR=0.66; P≤0.001), and 32% (IRR=0.68; P<0.001) lower in frequent users after 3, 6, 9, and 12 months, respectively, versus nonusers. Sustained technique failure risk at 3, 6, 9, and 12 months was 33% (hazard ratio [HR]=0.67; P=0.020), 31% (HR=0.69; P=0.003), 31% (HR=0.69; P=0.001), and 27% (HR=0.73; P=0.001) lower, respectively, in frequent users versus nonusers. Among a subgroup of survivors of the 12-month follow-up, sustained technique failure risk was 26% (HR=0.74; P=0.023) and 21% (HR=0.79; P=0.054) lower after 9 and 12 months, respectively, in frequent users versus nonusers. Conclusions: Our findings suggest frequent use of an RTM application associates with less hospital admissions, shorter hospital length of stay, and lower technique failure rates. Adoption of RTM applications may have the potential to improve timely identification/intervention of complications.

Urea kinetics during sustained low-efficiency dialysis in critically ill patients requiring renal replacement therapy.

Continuous renal replacement therapies have practical and theoretical advantages compared with conventional intermittent hemodialysis in hemodynamically unstable or severely catabolic patients with acute renal failure (ARF). Sustained low-efficiency dialysis (SLED) is a hybrid modality introduced July 1998 at the University of Arkansas for Medical Sciences that involves the application of a conventional hemodialysis machine with reduced dialysate and blood flow rates for 12-hour nocturnal treatments. Nine critically ill patients with ARF were studied during a single SLED treatment to determine delivered dialysis dose and the most appropriate model for the description of urea kinetics during treatment. Five patients were men, mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 28.9 and mean weight was 92.5 kg. Kt/V was determined by the reference method of direct dialysate quantification (DDQ) combined with an equilibrated postdialysis plasma water urea nitrogen (PUN) concentration and four other methods that were either blood or dialysate based, single or double pool, or model independent (whole-body kinetic method). Solute removal indices (SRIs) were determined from net urea removal and urea distribution volume supplied from DDQ (reference method) and by mass balance using variables supplied from blood-based formal variable-volume single-pool (VVSP) urea kinetic modeling. Equivalent renal urea clearances (EKRs) were calculated from urea generation rates and time-averaged concentrations for PUN based on weekly mass balance with kinetic variables supplied by either DDQ (reference method) or formal blood-based VVSP modeling. Mean Kt/V determined by the reference method was 1.40 and not significantly different when determined by formal VVSP modeling, DDQ using an immediate postdialysis PUN, or the whole-body kinetic method. Correction of single-pool Kt/V by a Daugirdas rate equation did not yield plausible results. Mean SRI and EKR by the reference methods were 0.61 and 24.8 mL/min, respectively, and not significantly different when determined by blood-based methods. A single-pool urea kinetic model adequately described intradialytic PUN profiles, indicating that SLED was associated with minimal urea disequilibrium. This was supported by the parity between hemodialyzer and whole-body urea clearances, and the mean postdialytic urea rebound of 4.1% (P = 0.13 versus zero). Additional prospective studies are needed in this setting to define the optimal method for dialysis quantification, targets for azotemic control, and optimal modality of renal replacement therapy. In conclusion, SLED delivers a high dose of dialysis with minimal associated urea disequilibrium and can be quantified by Kt/V, SRI, and EKR from blood-based methods using single-pool urea kinetic models.