High Water Intake in Polycystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease (PKD) affects 12.5 million people worldwide, and accounts for 7% of those requiring renal replacement therapy. The hormone vasopressin drives cyst growth until ultimately most of the normal functioning kidney tissue is replaced and compressed by cysts over the life course. Half of those affected will require dialysis by the age of 55 years.

Vasopressin blockade has emerged as a viable strategy for altering disease course. High water intake suppresses vasopressin, and may therefore slow cyst growth and consequent disease progression. However, evidence to support high water intake in PKD is lacking, and it is not clear whether patients can adhere sufficiently to a high water intake.

DRINK is a single-centre prospective, open label, parallel group randomised controlled feasibility trial. The primary objective is to establish whether a definitive large randomised trial comparing high versus ad libitum water intake on long-term disease progression is deliverable. Fifty patients will be recruited from the Renal Genetics service at Addenbrooke's Hospital. Participants will be randomly allocated to the high water intake (high) or the ad libitum (standard) water intake group. For the high intake group the aim is to drink large enough volumes of water to achieve and maintain dilute urine (urine osmolality < 270 mOsmo/kg or urine specific gravity ≤ 1.010 ). Multiple methods will be employed to promote adherence these include instruction and education as well as self-monitoring of urine specific gravity twice weekly by participants and the recording of results via a trial specific smartphone application.

Inclusion criteria

• Have given written informed consent to participate
• Aged 16 years or older
• Have a diagnosis of ADPKD (fulfilling radiological diagnostic criteria ± genetic evidence)
• eGFR ≥ 20ml/min/1.73m2
• Able to self-monitor urine SG

Exclusion criteria

• Inability to provide informed consent
• eGFR < 20ml/min/1.73m2
• Fluid overload states e.g. heart failure, cirrhosis, or requirement for fluid restriction
• Confounding illness impacting on renal disease e.g. concomitant diabetes or glomerulonephritis
• Treatment with diuretics for fluid overload (those on diuretics for hypertension may participate in the trial after a run-in period of 2 weeks)
• Treatment with Tolvaptan in the last 4 weeks
• Pregnancy or breastfeeding