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Background  The renal distal nephron plays an important role in the maintenance of sodium balance, extra cellular volume and blood pressure. The degree of water transport, via aquaporin2 water channels (AQP2), and sodium transport, via epithelial sodium channels (ENaC) in renal collecting duct principal cells are reflected by the level of urinary excretion of AQP2 (u-AQP2) and the γ-fraction of ENaC (u-ENaCγ). The effects of an acute intravenous volume load with isotonic saline, hypertonic saline and glucose on u-AQP2, u-ENaCγ and underlying mechanisms have never been studied in a randomized, placebo-controlled trial in healthy humans.    Methods  We studied the effects of 0.9% saline (23 ml/kg), 3% saline (7 ml/kg) and 5% glucose (23 ml/kg) on u-AQP2 and u-ENaCγ, fractional sodium excretion (FE Na ), free water clearance (C H2O ), and plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (ANG II) and aldosterone (Aldo) in a randomized, crossover study of 23 healthy subjects, who consumed a standardized diet, regarding calories, sodium and fluid for 4 days before each examination day.    Results  After isotonic saline infusion, u-AQP2 increased (27%). C H2O  and u-ENaCγ were unchanged, whereas FE Na  increased (123%). After hypertonic saline infusion, there was an increase in u-AQP2 (25%), u-ENaCγ (19%) and FE Na  (96%), whereas C H2O  decreased (-153%). After isotonic glucose infusion, there was a decrease in u-AQP2 (-16%), ENaCγ (-10%) and FE Na  (-44%) whereas C H2O  increased (164%). AVP remained unchanged after isotonic saline and glucose, but increased after hypertonic saline (139%). PRC, AngII and p-Aldo decreased after isotonic and hypertonic saline infusion, but not after glucose infusion.    Conclusions  Volume expansion with 3% and 0.9% saline increased u-AQP2, while isotonic glucose decreased u-AQP2. Infusion of hypertonic saline increased u-ENaCγ, whereas u-ENaCγ was not significantly changed after isotonic saline and tended to decrease after glucose. Thus, the transport of water and sodium is changed both via the aquaporin 2 water channels and the epithelial sodium channels during all three types of volume expansion to regulate and maintain water- and sodium homeostasis in the body.    Trial registration  Clinical Trial no:  NCT01414088

bmc nephrology

Effect of volume expansion with hypertonic- and isotonic saline and isotonic glucose on sodium and water transport in the principal cells in the kidney