Acute Cyclosporin a Renal Dysfunction in Dogs Reversed by Calcium Antagonists and Antiplatelet Agents

Abstract

The aim of this study was to assess the effect of nifedipine and piracetam alone or in combination in the protection of renal function and morphology after cyclosporin A (CyA) administration. Thirty healthy mongrel dogs with a mean body weight of 15 kg were sacrificed. Six animals (group C) were given CyA 20 mglkg body weight per os, while the remaining groups (8 animals each) were given concomitantly 20 mg nifedipine (group CN) or 4 g of piracetam (group CP), or both drugs in combination (group CNP). After 5 days of drug administration the animals were anesthetized, both kidneys were exposed, and functional tests were performed. Then the kidneys were removed for histological study. The mean plasma CyA levels in the four groups were 1765 ± 685 nglmL, 1300 ± 324 nglmL, 1116 ± 491 nglmL and 1600 ± 290 nglmL, respectively. Urine volume, creatinine, urea, and osmolar clearances were significantly higher in the groups CN, CP, and CNP compared to the control group C (p < 0.1). Urine sodium concentration was significantly higher (p < 0.05 or p < 0.01) in nifedipine groups than in the other two groups of animals, while the fractional excretion of sodium (FE_Na%) was significantly higher (p < 0.01) in all treated groups compared to controls. Plasma thromboxane-B2 levels were significantly reduced by each drug alone or in combination (p < 0.01). Morphological lesions, similar in all groups, did not correlate with the functional improvement. It is suggested that the effect of both drugs given separately or in combination is beneficial in terms of reduction of the CyA nephrotoxicity, through a decrease of the vasoconstrictor effect of TxB2.