Reduction of CyA Nephrotoxicity by Nifedipine During and After Experimental in Situ Renal Preservation

Abstract

In order to evaluate the role of nifedipine in the nephrotoxic effect induced by both ischemia and CyA, 18 healthy mongrel dogs were used. The kidneys were exposed and subjected to I h of ischemia by clamping both renal vessels. To the renal artery of the first group of kidneys (n = 9), 300 mL of cold Euro-Collins solution, in which nifedipine (Bay a 1040-10 mg) was diluted, was infused for 15 min (nifedipine group), while 300 mL of cold Euro-Collins solution plus 10 mg of placebo (Bay a 1040-placebo) was infused to the renal artery of the second group (n = 9) of kidneys (placebo group). Venous drainage was effected through a plastic cannula. All animals received through a nasogastric catheter 20 mglkg cyclosporine A at the beginning of the ischemia. The 1 h of ischemia was divided in a 15-min period of cold ischemia and 45-min of warm ischemia, at the end of which the clamps were removed. During the 2 h (30 min × 4) after reperfusion, 10 mg of nifedipine and placebo was administered additionally by a pe ipheral vein to the nifedipine and the placebo group, respectively. Then the kidneys were removed for histological study. Urine volume and creatinine and urea clearances of the nifedipine group were significantly higher than the placebo group (p < 0.001) while TxB2 levels were higher in the placebo group in all studied periods (p < 0.001). Urine sodium, FE_Nu, osmolar clearance, and LDH values were significantly different(p < 0.01), but the urine potassium concentration was not different in the two groups. The mean RBF after reperfusion was found to be 33.36 ± 9.8 mLlmin and 58.36 ± 21.02 in placebo and the nifedipine group, respectively (p < 0.01). We conclude that nifedipine is effective in the reduction of CyA nephrotoxicity during and after in situ renal preservation