TOXIC EFFECT OF CONCOMITANT ADMINISTRATION OF CYCLOSPORINE-A AND ACYCLOVIR ON RENAL-FUNCTION AND MORPHOLOGY IN RATS

The immunosuppressive agent cyclosporin A (CyA) and the antiviral drug acyclovir may cause renal functional impairment. CyA-induced immunosu ppression increases the rate of viral infections. Therefore we were in terested to determine whether short-term co-administration of CyA and acyclovir involves an increased nephrotoxic risk. Male Wistar rats wer e treated with CyA (20 mg/kg body wt., s.c., once daily for 8 days), a cyclovir (15 mg/kg body wt., s.c., 3-times daily for the last 5 days) or a combination of CyA and acyclovir. Blood levels of CyA were determ ined after a single dose. Urine was monitored for volume, osmolality, total protein and N-acetyl-beta-D-glucosaminidase (beta-NAG). Concentr ations of blood urea nitrogen (BUN) and plasma-creatinine were determi ned (day 9). Renal cortical slices were monitored for accumulation of weak organic acids (para-aminohippurate, PAH) and bases (tetra-ethylam monium, TEA) and for malondialdehyde (MDA) content. Renal histology wa s also examined. CYA induced a decrease in body and kidney weight, in urine osmolality and in the excretion of total protein. Plasma-creatin ine and BUN as well as MDA content of renal tissues were increased by CyA. Acyclovir alone did not induce significant changes. In comparison to CyA values, urine volume and beta-NAG excretion were enhanced and TEA accumulation depressed by the concomitant administration of CyA an d acyclovir. CyA- or acyclovir-treatment alone did not result in signi ficant morphological changes. In the group co-administered CyA/acyclov ir, the kidneys showed mild to moderate signs of tubulopathy. Short-te rm co-administration of CyA and acyclovir was concluded to have possib ly increased nephrotoxic potential.