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 leukocyte infiltration. In diverse models of renal failure, L-arginine supplementation improved hemodynamics and reduced inflammation. However in a proinflammatory environment, L-arginine can worsen renal injury. This study investigated the therapeutic potential of L-arginine supplementation in allogeneic renal transplantation: Brown Norway rat kidneys were transplanted into Lewis 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 drinking water for 7 d posttransplantation. Transplantation increased renal vasoconstriction (from 16.9 +/- 1.33 to 35.1 +/- 8.6 units; P: < 0.01), thereby reducing GFR (from 0.96 +/- 0.09 to 0.48 +/- 0.10 ml/min; P: < 0.05). Treatment 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 less inflammation, endothelial disruption, and thrombosis. L-arginine also decreased tubulitis, interstitial injury, and macrophage infiltration. These protective effects suggest that L-arginine might be useful as additive therapy to conventional immune suppression.
Vos
Ingrid H C
IHC
Department of Nephrology and Hypertension, University Medical Center, Utrecht, the Netherlands.
Rabelink
Ton J
TJ
Department of Vascular Medicine, University Medical Center, Utrecht, the Netherlands.
Dorland
Bert
B
Department of Laboratory of Metabolic Diseases, Wilhelmina Children's Hospital, Utrecht, the Netherlands.
Loos
Remko
R
Department of Laboratory of Metabolic Diseases, Wilhelmina Children's Hospital, Utrecht, the Netherlands.
Middelaar
Ben VAN
BV
Department of Nephrology and Hypertension, University Medical Center, Utrecht, the Netherlands.
Gröne
Hermann-Josef
HJ
Department of Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany.
Joles
Jaap A
JA
Department of Nephrology and Hypertension, University Medical Center, Utrecht, the Netherlands.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D012079:Renal Circulation / Q000187:drug effects; D014184:Transplantation, Homologous
D000893:Anti-Inflammatory Agents; D001120:Arginine