Effect of increased water intake on plasma copeptin in patients with chronic kidney disease: results from a pilot randomised controlled trial

OBJECTIVES: Increased water intake may have a beneficial effect on the kidney through suppression of plasma vasopressin. We examined the effect of increased water intake on plasma copeptin (a marker of vasopressin) over 6 weeks in patients with chronic kidney disease. DESIGN: Secondary analysis of a randomised controlled parallel-group pilot trial. SETTING: Canada, 2012-2013. PARTICIPANTS: 28 patients with stage 3 chronic kidney disease randomised (2:1) to a hydration (n=17) or control group (n=11). INTERVENTION: The hydration group was coached to increase water intake by up to 1.5 L/day for 6 weeks. The control group was asked to maintain regular water intake. MEASURES AND OUTCOMES: Participants provided blood and 24 h urine samples at baseline and 6 weeks. Change in plasma copeptin was compared within and between study groups. RESULTS: Participants were 64% male with a mean age of 62 years and an estimated glomerular filtration rate of 40 mL/min/1.73 m(2). Between baseline and 6 weeks, 24 h urine volume increased by 0.7 L/day in the hydration group, rising from 2.3 to 3.0 L/day (p=0.01), while decreasing by 0.3 L/day among controls, from 2.0 to 1.7 L/day (p=0.07); between-group difference: 0.9 L/day (95% CI 0.37 to 1.46; p=0.002). In the hydration group, median copeptin decreased by 3.6 pmol/L, from 15.0 to 10.8 pmol/L (p=0.005), while remaining stable among controls at 19 pmol/L (p=0.76; p=0.19 for the between-group difference in median change); the between-group difference in mean change was 5.4 pmol/L (95% CI -1.2 to 12.0; p=0.11). CONCLUSIONS: Adults with stage 3 chronic kidney disease can be successfully randomised to drink approximately 1 L more per day than controls. This increased water intake caused a significant decrease in plasma copeptin concentration. Our larger 12-month trial will examine whether increased water intake can slow renal decline in patients with chronic kidney disease. TRIAL REGISTRATION NUMBER: NCT01753466.