ET-1 excretion is urine flow-dependent in kidney donors and transplant recipients

Urinary endothelin-1 excretion (uET-1/min) has been reported to be elevated under cyclosporin A (CsA) therapy in kidney transplant recipients (KR). The possible flow-dependence of uET-1/min was not considered. Therefore, we studied the effect of water diuresis on uET-1/min in KR 1 year after transplantation and used kidney donors (KD) as controls. Urinary ET-1/min and urine flow (uFlow) were measured in 25 KR and in 21 KD before and 27 KD 1 year after surgery (KD-Nx) during water diuresis induced by oral hydration in a 12 h overnight collection. uET-1/min was correlated with uFlow. uET-1/min in 12-h overnight collection was similar in KD, KD-Nx, and KR (127 +/- 55, 110 +/- 42, and 122 +/- 53 pg/min respectively). Urine flow did not differ significantly among the three groups (range 0.6-3.7 ml/min). uET-1/min correlated significantly with urine flow in KD, KD-Nx, and KR (r = 0.59, r = 0.42, and r = 0.53, p < 0.03, respectively). The slope of the three regression lines was not different. There was no correlation of uET-1/min with CsA trough level or dose. uET-1/min is urine flow-dependent during water diuresis. Because NaCl diuresis has been reported to have no influence on uET-1/min, we hypothesize that uET-1/min is linked to the state of diuresis or antidiuresis in the distal nephron. CsA therapy does not influence uET-1/min in a 12-h urine collection.