title: Long-term dietary L-arginine supplementation attenuates proteinuria and focal glomerulosclerosis in experimental chronic renal transplant failure.
abstract: Glomerular endothelial nitric oxide synthase expression is decreased in humans during acute rejection and chronic renal transplant failure (CRTF). This may contribute to vascular damage through changes in the renal hemodynamics and enhanced endothelial adhesion of leukocytes and platelets. Dietary supplementation of L-arginine may increase endothelial NO production, thereby protecting the vascular wall and improving renal hemodynamics. We tested the hypothesis that long-term L-arginine supplementation attenuates the development of CRTF in an experimental model for renal transplantation. In the Fisher 344 to Lewis rat model for renal transplantation, renal function and histology of untreated rats was compared with rats receiving L-arginine in the drinking water (10g/L), starting 2 days before transplantation. Every 4 weeks systolic blood pressure was measured and serum and urine were collected for measurement of nitrite and nitrate (NO(x)), creatinine, and proteinuria. At 34 weeks the histological renal damage was assessed by scoring focal glomerulosclerosis and measurement of alpha-smooth muscle actin (alpha-SMA) expression. Urinary NO(x) was significantly increased in treated animals. Proteinuria was significantly lower in L-arginine-treated animals from week 24 onward (p<0.05). Plasma creatinine and creatinine clearance did not differ between the groups. The focal and segmental glomerulosclerosis (FGS) score (max 400) at week 34 was also significantly lower in treated rats arbitrary U (20+/-21 vs 61+/-67 arbitrary U; p<0.05). The expression of alpha-SMA was lower in L-arginine-treated rats than in untreated rats (1.93+/-0.8% area surface vs 3.64+/-2.5% area surface). In conclusion, in this experimental model for CRTF, L-arginine administration significantly reduced FGS and proteinuria, without affecting renal function. Our data suggest that dietary L-arginine supplementation attenuates progression of CRTF and may therefore be an additional therapeutic option in human renal allograft recipients.
authors.affiliation: Department of Pathology and Laboratory Medicine, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. e.albrecht@path.azg.nl
authors.forename: Ester W J A
authors.initials: EW
authors.lastname: Albrecht
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Annemieke
authors.initials: A
authors.lastname: Smit-van Oosten
authors.forename: Coen A
authors.initials: CA
authors.lastname: Stegeman
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003401:Creatine / Q000097:blood; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications* / Q000178:diet therapy* / Q000517:prevention & control; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000178:diet therapy* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D009566:Nitrates / Q000652:urine; D009573:Nitrites / Q000652:urine; D011507:Proteinuria / Q000150:complications* / Q000178:diet therapy* / Q000517:prevention & control; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D009566:Nitrates; D009573:Nitrites; D001120:Arginine; D003401:Creatine