Medium-term cyclosporin renal dysfunction and its reversibility in rats

Renal dynamics and morphol-ogy 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 <0.05) and was further impaired in groups CsA 20 and CsA 30 (-45%, P <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 <0.01) after the fall of glomerular capillary pressure (P_gc; -8%, P <0.05), the increase of afferent arteriole resistance (R_a; +40%, P <0.05), and the consequent decrease of glomerular plasma flow (GPF; -28%, P <0.05). Thirty days after CsA withdrawal, SNGFR returned to normal values (P <0.01 vs. group CsA) as a result of the normalization of P_gc, R_a, 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.