The Chronic Kidney Disease Water Intake Trial: Protocol of a Randomized Controlled Trial.

BACKGROUND

In observational studies, drinking more water associates with a slower rate of kidney function decline; whether the same is true in a randomized controlled trial is unknown.

OBJECTIVE

To examine the 1-year effect of a higher vs usual water intake on estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease.

DESIGN

Parallel-group randomized controlled trial.

SETTING

Nine centers in Ontario, Canada. Enrollment and randomization occurred between May 2013 and May 2016; follow-up for the primary outcome will continue until June 2017.

PARTICIPANTS

Adults (n = 631) with stage 3 chronic kidney disease (eGFR 30-60 mL/min/1.73 m) and microalbuminuria.

INTERVENTION

The high water intake group was coached to increase their oral water intake by 1.0 to 1.5 L/day (depending on sex and weight), over and above usual consumed beverages, for a period of 1 year. The control group was coached to maintain their usual water intake during this time.

MEASURES

Participants provided 24-hour urine samples at baseline and at 6 and 12 months after randomization; urine samples were analyzed for volume, creatinine, osmolality, and the albumin-to-creatinine ratio. Blood samples were obtained at baseline and at 3- to 6-month intervals after randomization, and analyzed for creatinine, copeptin, osmolality, and electrolytes. Other measures collected included health-related quality of life, blood pressure, body mass index, and diet.

PRIMARY OUTCOME

The between-group change in eGFR from baseline (prerandomization) to 12 months after randomization.

SECONDARY OUTCOMES

Change in plasma copeptin concentration, 24-hour urine albumin-to-creatinine ratio, measured creatinine clearance, estimated 5-year risk of kidney failure (using the 4-variable Kidney Failure Risk Equation), and health-related quality of life.

PLANNED ANALYSIS

The primary analysis will follow an intention-to-treat approach. The between-group change in eGFR will be compared using linear regression. Supplementary analyses will examine alternative definitions of eGFR change, including annual percentage change, rate of decline, and rapid decline (a value <0.05 will be interpreted as statistically significant if there is concordance with the primary outcome).

TRIAL REGISTRATION

This randomized controlled trial has been registered at www.clinicaltrials.gov; government identifier: NCT01766687.