The predictive value of enzymuria in cyclosporin A-induced renal toxicity in the rat.
The acute nephrotoxic properties of cyclosporin A (CsA) were investigated in normotensive, adult male Sprague-Dawley rats. Animals received either 50 or 100 mg CsA/kg by gastric intubation for 7 days. Within 24 h, significant increases in urinary N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma GT) activity were observed at both doses of CsA. Renal function abnormalities, however, were not apparent until 2 days (100 mg/kg) or 7 days (50 mg/kg). Progressive increases in enzymuria were evident in both groups between 1 and 4 days, at which later time proximal straight tubular cell damage was first observed. The data obtained using this model clearly demonstrate that enzymuria provides a sensitive index of acute CsA-induced renal cell damage and that enzymuria precedes detectable renal functional and structural abnormalities.
D000118:Acetylglucosaminidase / Q000652:urine*; D000818:Animals; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006596:Hexosaminidases / Q000652:urine*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014508:Urea / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000652:urine*
D003524:Cyclosporins; D014508:Urea; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D006596:Hexosaminidases; D000118:Acetylglucosaminidase