The prescription of hemodialysis (HD) in patients with incident end-stage kidney disease (ESKD) is fundamentally empirical. The abrupt transition from nondialysis chronic kidney disease (CKD) to thrice-weekly in-center HD of much the same dialysis intensity as in those with prevalent ESKD underappreciates the progressive nature of kidney disease whereby the decline in renal function has been gradual and ongoing-including at the time of HD initiation. Adjuvant pharmacologic treatment (i.e., diuretics, acid buffers, potassium binders), coupled with residual kidney function (RKF), can complement an initial HD regimen of lower intensity. Barriers to less intensive HD in incident ESKD include risk of inadequate clearance of uremic toxins due to variable and unexpected loss of RKF, lack of patient adherence to assessments of RKF or adjustment of HD intensity, increased burden for all stakeholders in the dialysis units, and negative financial repercussions. A stepped dialysis regimen with scheduled transition from time-delineated twice-weekly HD to thrice-weekly HD could represent an effective and safe strategy to standardize incremental HD in patients with CKD transitioning to early-stage ESKD. Patients' adherence and survival as well as other clinical outcomes should be rigorously evaluated in clinical trials before large-scale implementation of different incremental schedules of HD. This review discusses potential benefits of and barriers to alternative dialysis regimens in patients with incident ESKD, with emphasis on twice-weekly HD with pharmacologic therapy, and summarizes in-progress clinical trials of incremental HD schedules.

Introduction

The optimal haemodialysis (HD) prescription-frequency and dose-for patients with incident dialysis-dependent kidney disease (DDKD) and substantial residual kidney function (RKF)-that is, renal urea clearance ≥2 mL/min/1.73 m² and urine volume ≥500 mL/day-is not known. The aim of the present study is to test the feasibility and safety of a simple, reliable prescription of incremental HD in patients with incident DDKD and RKF.

Methods and analysis

This parallel-group, open-label randomised pilot trial will enrol 50 patients from 14 outpatient dialysis units. Participants will be randomised (1:1) to receive twice-weekly HD with adjuvant pharmacological therapy for 6 weeks followed by thrice-weekly HD (incremental HD group) or outright thrice-weekly HD (standard HD group). Age ≥18 years, chronic kidney disease progressing to DDKD and urine output ≥500 mL/day are key inclusion criteria; patients with left ventricular ejection fraction <30% and acute kidney injury requiring dialysis will be excluded. Adjuvant pharmacological therapy (ie, effective diuretic regimen, patiromer and sodium bicarbonate) will complement twice-weekly HD. The primary feasibility end points are recruitment rate, adherence to the assigned HD regimen, adherence to serial timed urine collections and treatment contamination. Incidence rate of clinically significant volume overload and metabolic imbalances in the first 3 months after randomisation will be used to assess intervention safety.

Ethics and dissemination

The study has been reviewed and approved by the Institutional Review Board of Wake Forest School of Medicine in North Carolina, USA. Patient recruitment began on 14 June 2019, was paused between 13 March 2020 and 31 May 2020 due to COVID-19 pandemic, resumed on 01 June 2020 and will last until the required sample size has been attained. Participants will be followed in usual care fashion for a minimum of 6 months from last individual enrolled. All regulations and measures of ethics and confidentiality are handled in accordance with the Declaration of Helsinki.

Trial registration number

NCT03740048; Pre-results.