Medium-term cyclosporin renal dysfunction and its reversibility in rats

Abstract

Renal dynamics and morphology were investigated by metabolic, renal micropuncture (RM), and electron microscopy (EM) studies in 50 female rats treated with cyclosporin A (CsA, 40 mg.kg body wt-1.48 h-1) for either 10, 20, or 30 days (groups CsA 10, CsA 20, and CsA 30, respectively); control rats received olive oil (group N). Body weight gain, sodium metabolism, and plasma volume were not altered by CsA administration in any group. GFR was decreased in group CsA 10 vs. group N (-10%, P less than 0.05) and was further impaired in groups CsA 20 and CsA 30 (-45%, P less than 0.01 vs. group N). RM studies showed a significant decrease of single-nephron glomerular filtration rate (SNGFR) in group CsA 30 vs. group N (-26%, P less than 0.01) after the fall of glomerular capillary pressure (Pgc;-8%, P less than 0.05), the increase of afferent arteriole resistance (Ra; +40%, P less than 0.05), and the consequent decrease of glomerular plasma flow (GPF; -28%, P less than 0.05). Thirty days after CsA withdrawal, SNGFR returned to normal values (P less than 0.01 vs. group CsA) as a result of the normalization of Pgc, Ra, and GPF.EM showed only a progressive vacuolation of proximal and distal tubular cells. These data suggest that medium-term administration of CsA is associated with reversible changes in glomerular dynamics and only mild histological lesions.