Nephrotoxicity of cyclosporine A in rats with a diminished renal function

We have studied the effect of cyclosporine A (CyA) in male Wistar rats with only one kidney, that had been subjected to 45 min of warm ischemia (IS + NX). The effects were compared with those obtained in rats with either one (NX) or two intact kidneys (2K). Vehicle treated rats that underwent the same surgical procedure served as controls. The GFR and the ERPF were determined during and after the treatment period. The CyA was administered i.m. daily for a period of 5 days a week for a period of 4 weeks. The dosages were 15, 30, or 60 mg/kg/day in the short-term study, and 15 mg/kg/day in the long-term study. With only 5 days of treatment, changes in the GFR induced by CyA were more pronounced in IS + NX rats when compared with NX rats. Furthermore, in contrast with NX rats, the GFR did not completely recover in IS + NX rats. During the 4 week treatment we found that in all 3 models the GFR was less in the CyA treated rats than in the vehicle treated rats. The degree of impairment of the GFR differed in the various models. At the end of the treatment period, the GFR of the CyA treated rats (expressed as a percentage of the vehicle treated rats) amounted to 84% in 2K rats, 64% in NX rats, and 46% in IS + NX rats. After cessation of the CyA administration, there was a complete recovery of the GFR to control levels in 2K and NX rats. In IS + NX rats, however, the GFR remained significantly below that of vehicle treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)