Effect of hepatocyte growth factor on tacrolimus-induced nephrotoxicity in spontaneously hypertensive rats.

Renal toxicity is a serious side effect of therapy with tacrolimus (FK506), an immunosuppressive agent administered to renal transplant recipients. We investigated the effect of hepatocyte growth factor (HGF) on tacrolimus-induced nephrotoxicity in spontaneously hypertensive rats (SHR). After a right nephrectomy, rats received a continuous perfusion of either HGF in a dose of 5 microg/kg daily (tacrolimus + HGF group) or normal saline (tacrolimus group) into the left renal artery at a rate of 1 microl/h for 7 days after surgery. Tacrolimus was injected intramuscularly in a dose of 4 mg/kg daily for 10 days after surgery. HGF significantly inhibited the tacrolimus-induced increase in the serum creatinine (SCr) level (P < 0.05). HGF also prevented the tacrolimus-induced loss in body weight. The bromodeoxyuridine (BrdU) index was significantly higher in kidney specimens from the tacrolimus + HGF group. These findings suggest that HGF induces the regeneration of renal tubular cells and suppresses tacrolimus-induced renal toxicity in SHR.