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

Abstract

Nephrotoxicity is one of the main side effects of calcineurininhibitors. The influence of tacrolimus on the renal vasculature has not been well described. We have therefore examined the effects of tacrolimus on renal functional parameters as well as the contribution of the NO-system in a model of ischemic acute renal failure (ARF). Induction of ARF was achieved by clamping both renal arteries of female Sprague-Dawley rats. During the experiment, RBF, GFR, MAP, RVR and FENa were determined during infusion of vehicle, TAC, 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 Larginine-infusion could reverse these effects during the infusion without complete restoration to preischemic levels. NOS-inhibition 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 vessels with a further deterioration of renal function. Larginine abolishes the functional deterioration, most likely due to increased NO-liberation.

Pharmacokinetics, Biodistribution, Stability and Toxicity of a Cell-Penetrating Peptide−Morpholino Oligomer Conjugate

“…Free l -arginine was administered ad libitum in an attempt to restore BUN and serum creatinine to the normal plasma levels alongside treatment with CPP−PMO at a dose of 150 mg/kg. This was based on earlier reports demonstrating l -arginine to be effective against renal toxic or ischemic injury ( − ). l -Arginine supplementation significantly improved BUN ( p < 0.01)) and serum creatinine ( p < 0.05) clearance, as shown in Figure A and B, respectively.…”

“…Displacement of the CPP−PMO conjugate from the transporter by l -arginine may lead to reduced kidney exposure, and hence, the effect of the CPP−PMO on the kidney could be reduced. Also, l -arginine has been shown to increase renal glomerular filtration rate (GFR) either via nitric oxide (NO) production or stimulation of glucagon secretion ( − ). Indeed, our results showed improved renal clearance of creatinine and BUN following l -arginine supplementation.…”

Amelioration of Rhabdomyolysis-Induced Myoglobinuric Acute Renal Failure by Citrullus lanatus Seeds

“…[29] Another mechanism may involve the protective effect of exogenous L-arginine against toxic or ischemic injury to the kidneys that have been shown in several studies. [30] However, the molecular processes underlying these positive effects are unknown, but L-arginine is thought to be a substrate for NO synthesis (NOS) [31] through NOS. [32] This mechanism is responsible for metabolizing about 1% of daily L-arginine consumption.…”