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.