Tacrolimus in acute renal failure: does L-arginine-infusion prevent changes in renal hemodynamics?

Nephrotoxicity is one of the main side effects of calcineurin-inhibitors. T he influence of tacrolimus on the renal vasculature has not been well descr ibed. We have therefore examined the effects of tacrolimus on renal functio nal parameters as well as the contribution of the NO-system in a model of i schemic acute renal failure (ARF). Induction of ARF was achieved by clampin g both renal arteries of female Sprague-Dawley rats. During the experiment, RBF, GFR, MAP, RVR and FENa were determined during infusion of vehicle, TA G, TAC and the NOS-activator L-arginine, and TAC and NOS-inhibition due to L-NMMA. TAC induced a significant rise in RVR with further decrease of RBF and GFR. Simultaneous L-arginine-infusion could reverse these effects durin g the infusion without complete restoration to preischemic levels. NOS-inhi bition increased MAP and RBF without any effect on GFR. FENa did not differ significantly between the groups. Tacrolimus in the situation of ischemic acute renal failure causes vasoconstriction of pre- and postglomerular vess els with a further deterioration of renal function. L-arginine abolishes th e functional deterioration, most likely due to increased NO-liberation.