The effect of renal ischemia on cyclosporine clearance in rabbits

The renal handling of cyclosporine was studied in ischemically damaged kidneys in New Zealand White rabbits and nonischemic control animals. CsA, 25 mg/kg/day, was administered intravenously for 10 days starting with the day of operation. Blood CsA (B CsA) was higher in the ischemic group compared with the controls (median: 285 micrograms/L, range 95-785 micrograms/L vs. 170 micrograms/L, range 110-185 micrograms/L, P = 0.05) on day 1 after operation. B CsA dropped rapidly to a level equivalent to the controls by day 4 (median: 105 micrograms/L, range 60-280 micrograms/L vs. 195 micrograms/L, range 70-215 micrograms/L, P = NS). Median CsA clearance (C CsA) as a percentage of creatinine clearance (C Cr) was some ten-fold greater in the ischemic animals (6.32%, range 2.93-18.41% vs. 0.55%, range 0.13-0.78%, P less than 0.001) on day 1. The ratio gradually declined, approaching the value in controls by day 10 (0.86%, range 0.24-7.21% vs. 0.23%, range 0.16-0.73%, P = 0.05). The data suggest that renal impairment has an important effect on CsA blood levels. In the clinical situation this may be of particular importance during both oliguria and the recovery from acute tubular necrosis.