Randomised controlled trial of high versus ad libitum water intake in patients with autosomal dominant polycystic kidney disease: rationale and design of the DRINK feasibility trial.

Abstract

Introduction Vasopressin stimulates cyst growth in Autosomal Dominant Polycystic Kidney Disease (ADPKD) leading to enlarged kidneys, hypertension and renal failure. Vasopressin receptor blockade slows disease progression. Physiological suppression of vasopressin secretion through high water intake could achieve a similar effect, necessitating a definitive large-scale trial of high water intake in ADPKD. The objective of the DRINK trial is to answer the key design and feasibility questions required to deliver a successful definitive water intake trial. Methods and Analysis We describe the design of a single-centre, open label, prospective, randomised controlled trial. DRINK aims to enroll 50 ADPKD patients, over the age 16years with an eGFR≥20ml/min/1.73m2. Participants will be randomised 1:1 to high water (HW) intake based on an individualised water intake prescription, or to ad libitum(AW) water intake. The HW group will aim for a dilute urine (urine osmolality≤270mOsmo/kg) as a surrogate marker of vasopressin suppression, and those in the AW group will target more concentrated urine. Participants will have an 8week treatment period, and will be seen at week 0, 2,4 and 8, undergoing assessments of fluid status, renal function and serum and urine osmolalities. They will receive dietary advice, and self-monitor urine specific gravity and fluid intake. The trial employs smartphone technology to permit home monitoring and remote direct data capture. The primary feasibility endpoints are recruitment rate and separation between arms in measured urinary osmolality. Key secondary assessments include acceptability, adherence, health-related quality of life, acute effects of high water intake on measured (51Cr-EDTA) and estimated glomerular filtration rate, and ADPKD-related pain. Ethics and Dissemination Ethical approval was awarded by the East of England Essex Research Ethics Committee (16/EE/0026). The results of DRINK will be submitted to peer reviewed journals, and presented to patients via the PKD Charity. Trial Registration Details: NCT02933268 and ISCRTN1679495