The effect of rapamycin on kidney function in the Sprague-Dawley rat.
The effects of rapamycin (RAPA) on kidney function and histology were investigated in the Sprague-Dawley rat and compared with cyclosporine. Drugs were administered orally in a Cremophor-ethanol formulation for 14 days in two separate studies. RAPA, at 1 mg/kg, had no effect either functionally or histologically on the kidney. At 10 mg/kg, RAPA depressed the gain in body weight by 20% in the rat but had only minor functional disturbances on urine output, plasma creatinine, and creatinine clearance in the kidney. It did not induce any histomorphologic abnormalities. CsA, at 25 mg/kg, produced functional alterations in the kidney including elevated plasma creatinine and depressed clearance of creatinine as well as depressed body weight gain (17%). Histologically, CsA induced proximal tubule damage. These results demonstrate that RAPA (10 mg/kg) does not produce nephrotoxicity in the Sprague-Dawley rat at doses three times higher than its effective immunosuppressive doses established in the rat.
DiJoseph
J F
JF
Department of Experimental Therapeutics, Wyeth-Ayerst Research, Princeton, New Jersey 08543-8000.
Sharma
R N
RN
Chang
J Y
JY
D000818:Animals; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000033:anatomy & histology / Q000502:physiology*; D008297:Male; D009929:Organ Size; D009994:Osmolar Concentration; D011090:Polyenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D020123:Sirolimus; D014556:Urine; D015430:Weight Gain
D007166:Immunosuppressive Agents; D011090:Polyenes; D016572:Cyclosporine; D003404:Creatinine; D020123:Sirolimus