Sub-nephrotoxic cisplatin sensitizes rats to acute renal failure and increases urinary excretion of fumarylacetoacetase

摘要: Nephrotoxicity limits the therapeutic efficacy of antineoplastic drug cisplatin. Due to dosage adjustment and appropriate monitoring, most courses with cisplatin produce no or minimal kidney damage. However, we studied whether even sub-nephrotoxic poses a potential risk for kidneys by predisposing acute injury (AKI), specifically lowering toxicity threshold second nephrotoxin. With this purpose rats were treated single (3mg/kg, i.p.) after two days, regime gentamicin (50mg/kg/day, during 6 i.p.). Control groups received only one drugs vehicle. Renal function renal histology monitored throughout experiment. Cisplatin treatment did not cause any relevant functional histological alterations in kidneys. Rats gentamicin, but those under treatments, developed an overt failure characterized both dysfunction massive tubular necrosis. In addition, urinary excretion fumarylacetoacetase was increased cisplatin-treated animals at subtoxic doses, which might be exploited as cisplatin-induced predisposition marker. fact, level prior nephrotoxin correlated AKI triggered predisposed animals.