Acute reversal of cyclosporine nephrotoxicity by neutral endopeptidase inhibition in stable renal transplant recipients

Atrial natriuretic peptide and cyclosporine have opposing effects on renal hemodynamics and excretory function. Twelve male stable cyclosporine-treated renal transplant recipients received a single 100-mg i.v. dose of the neutral endopeptidase EC 24.11 inhibitor candoxatrilat in a double-blind, placebo-controlled cross-over study. Each study day consisted of 2 hr of baseline and 7 hr of postdose evaluation. After administration of candoxatrilat, plasma atrial natriuretic factor rose from 12.8+/-1.6 (mean +/- SEM) to 44.1+/-6.8 pmol/L (P