[Nephrotoxicity of the combination of cyclosporin and aminoglycoside in rats. Comparative study of gentamicin and amikacin].

The renal toxicity of combined administration of cyclosporin and aminoglycosides was evaluated in rats. Increasing doses of amikacin (A) or gentamicin (G) were injected alone or in association with cyclosporin (CS). Creatinine clearance rate, urinary N-acetyl-Beta-D-glucosaminidase (NAG) activity and NAG-B isoenzyme level were determined to evaluate glomerular or tubular dysfunctions. When given alone, high doses of aminoglycosides (100 mg/kg/day of G and 375 mg/kg/day of A) induced transient inhibition of glomerular filtration rate. The concomitant administration of CS caused severe acute renal failures with 50 mg/kg/day of G and only with 375 mg/kg/day of A. With equal doses of G, urinary NAG excretion was seven times higher in association with CS than in monotherapy. In the same conditions, NAG activity was only doubled with A. A specific increased of NAG-B isoenzyme level occurred only during the most nephrotoxic association. This attest of a proximal tubular lesion, preliminary to glomerular dysfunction. The results of this study confirm the potent synergistic nephrotoxicity that CS exerts in combination with aminoglycosides. Nevertheless, the good tolerance of amikacin lead us to reconsider the principle of exclusion of such association in transplant recipients.