Influence of hepatic ischemia-reperfusion injury on tacrolimus acute renal toxicity in pigs.

H T E DEVELOPMENT of new immunosuppressants has been a determining factor in the recent surge in organ transplants. Tacrolimus, which was introduced in clinical practice by Starzl in 1989, has proved to be useful for prevention and treatment of rejection. Among its side effects, nephrotoxicity is of particular importance. The precipitating causes of acute nephrotoxicity (ANT), which may affect 35% to 45% of liver transplant patients are uncertain, but possibly include early graft malfunction, a phenomenon related to ischemia and reperfusion injuries, which result at least in part from shortcomings in the organ preservation. To shed light on the relationship between ischemic liver injury and ANT caused by tacrolimus, we designed a comparative experimental study of the kidney damage generated in two experimental models of hepatic ischemia-reperfusion injury: non–heart-beating donor and an ischemia–reperfusion model with the organ in situ.