Protein-enriched diet increases water absorption via the aquaporin-2 water channels in healthy humans.

Background: According to animal experiments, a protein-enriched diet increased renal absorption of sodium and water. We wanted to test the hypothesis that a protein-enriched diet would increase the expression of the aquaporin-2 water channels and the epithelial sodium channels in the distal part of the nephron using biomarkers for the activity of the two channels.

Methods: We performed a randomized, placebo controlled crossover study in 13 healthy humans to examine the effect of a protein-enriched diet on renal handling of water and sodium during baseline condition and during hypertonic saline infusion. We measured the effect of the protein-enriched diet on urinary excretions of aquaporin-2 (u-AQP2), the beta-fraction of the epithelial sodium channels (u-ENaC(beta)), free water clearance (C(H2O)), fractional excretion of sodium and vasoactive hormones.

Results: During baseline conditions, u-AQP2 increased, and C(H2O) decreased during the protein-enriched diet, whereas u-ENaC(beta) was unchanged, although the urinary sodium excretion increased. During hypertonic saline infusion, the response in the effect variables did not deviate between protein-enriched and normal diet. Plasma concentrations of angiotensin II and aldosterone increased as well as pulse rate. Vasopressin in plasma was unchanged, and prostaglandin E(2) fell during the protein-enriched diet.

Conclusions: The protein-enriched diet increased water absorption via an increased transport via the aquaporin-2 water channels. The increased u-AQP2 might be due to a reduced prostaglandin level. The increase in renal sodium excretion seems to be mediated in another part of the nephron than the epithelial sodium channels.