L-arginine supplementation improves function and reduces inflammation in renal allografts

Recovery from ischemia/reperfusion and immune-mediated injury in the renal transplant is associated with reduced renal hemodynamics and increased leuk ocyte infiltration. In diverse models of renal failure, L-arginine suppleme ntation improved hemodynamics and reduced inflammation. However in a proinf lammatory environment, L-arginine can worsen renal injury. This study inves tigated the therapeutic potential of L-arginine supplementation in allogene ic renal transplantation: Brown Norway rat kidneys were transplanted into L ewis rat recipients, with one native kidney remaining. Recipients received low-dose cyclosporin A (2.5 mg/kg per d subcutaneously) to obtain moderate vascular and interstitial rejection, with or without 1% L-arginine in drink ing water for 7 d posttransplantation. Transplantation increased renal vaso constriction (from 16.9 +/- 1.33 to 35.1 +/- 8.6 units; P < 0.01), thereby reducing GER (from 0.96 +/- 0.09 to 0.48 +/- 0.10 ml/min; P < 0.05). Treatm ent with L-arginine restored renal graft function to levels found in normal donors (renal vascular resistance, 15.7 +/- 1.69 units; GFR, 0.80 +/- 0.06 ml/min). L-arginine significantly reduced vascular occlusion because of le ss inflammation, endothelial disruption, and thrombosis. L-arginine also de creased tubulitis, interstitial injury, and macrophage infiltration. These protective effects suggest that L-arginine might be useful as additive ther apy to conventional immune suppression.