Effects of salt and protein intake on polyuria in V2RA-treated ADPKD patients

BACKGROUND: The only treatment proven to be renoprotective in Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a vasopressin V2-receptor antagonist (V2RA). However, aquaresis-associated side effects limit tolerability. We investigated whether salt and/or protein intake influences urine volume and related endpoints in V2RA-treated ADPKD patients.

METHODS: In this randomized, controlled, double-blind, crossover trial, ADPKD patients treated with maximally tolerated dose of a V2RA were included. While on a low salt and low protein diet, patients were given additional salt and protein to mimic regular intake, which was subsequently replaced by placebo in random order during four 2-week periods. Primary endpoint was change in 24-h urine volume. Secondary endpoints were change in quality of life, measured glomerular filtration rate (mGFR), blood pressure, and copeptin level.

RESULTS: Twelve patients (49±8 years, 25.0% male) were included. Baseline salt- and protein intake was 10.8±1.3 g/24-h and 1.2±0.2 g/kg/24-h. During the low salt and low protein treatment periods, intake decreased to 5.8±1.6 g/24-hand 0.8±0.1 g/kg/24-h, respectively. Baseline 24-h urine volume (5.9±1.2 L) decreased to 5.2±1.1 L (-11%, p=0.004) on low salt & low protein and to 5.4±0.9 L (-8%, p=0.04) on low salt. Reduction in 24-h urine volume was two times greater in patients with lower urine osmolality (-16 vs -7%). Polyuria QoL scores improved in concordance with changes in urine volume. mGFR decreased during the low salt & low protein, while mean arterial pressure did not change during study periods. Plasma copeptin decreased significantly during low salt & low protein periods.

CONCLUSION: Lowering dietary salt and protein intake has a minor effect on urine volume in V2RA-treated ADPKD patients. Reduced intake of osmoles decreased copeptin concentrations and might thus increase the renoprotective effect of a V2RA in ADPKD patients.