Effect of cyclosporine on renal ischemic injury.

To determine whether cyclosporine exacerbated renal ischemic injury and whether or not the timing of cyclosporine administration was important, rats were subjected to 30 or 45 min of ischemia. Cyclosporine was administered either before or after the renal ischemic insult. A single intravenous dose of cyclosporine, 20 mg/kg, before ischemia had no additional deleterious effect on inulin clearance compared with rats subjected to ischemia alone. In contrast, a significant exacerbation of the diminished glomerular filtration rate (GFR) produced by ischemia occurred when a low dose of cyclosporine (5 mg/kg) was given after ischemia. With 30 min of ischemia, GFR was 160 +/- 40 microliter/min/100 g in rats receiving cyclosporine (5 mg/kg) after ischemia compared with 280 +/- 40 microliter/min/100 g in rats subjected to ischemia alone. After 45 min of ischemia, cyclosporine (5 mg/kg) markedly reduced GFR to 20 +/- 10 microliter/min/100 g, a value significantly lower (P less than 0.05) than that observed in rats subjected to 45 min of ischemia alone (290 +/- 100 microliter/min/100 g). Plasma potassium concentrations tended to be higher and urinary potassium and sodium excretion lower in rats subjected to ischemia plus cyclosporine compared with ischemia alone. These findings indicate that even a single low dose of parenteral cyclosporine can exacerbate renal ischemic injury if given immediately after the ischemic insult. This interaction may contribute to the acute renal failure observed with cyclosporine use. In contrast, the kidney appears to be relatively resistant to a single dose of cyclosporine injury when the drug is administered prior to ischemia. These data suggest that the administration of parenteral cyclosporine immediately after transplantation could have deleterious effects and should probably be avoided.