L-arginine as a therapeutic tool in kidney disease.
Infusion of L-arginine in experimental animals increases renal plasma flow (RPF) and glomerular filtration rate (GFR). It is likely that a component of these hemodynamic changes are mediated by nitric oxide (NO) as suggested by studies with specific antagonists of L-arginine metabolism. L-arginine administration ameliorates the infiltration of the renal parenchyma by macrophages in rats with obstructive nephropathy or rats with puromycin-induced nephrotic syndrome. L-arginine administration also blunts the increase in interstitial volume, collagen IV, and alpha-smooth muscle actin. Rats with a remnant kidney given 1% L-arginine in the drinking water had a greater GFR and RPF. L-arginine administration also decreased proteinuria. Diabetic rats given L-arginine had significantly lower excretion of protein and cyclic guanosine monophosphate than diabetic rats not receiving L-arginine. Despite persistent hyperglycemia, the administration of L-arginine prevented the development of hyperfiltration and ameliorated proteinuria in diabetic rats. In the setting of ischemic acute renal failure, the administration of L-arginine had a beneficial effect on GFR and RPF, decreased O2- production, diminished up-regulation of soluble guanylate cyclase, and prevented up-regulation of inducible NO synthase (iNOS). The pharmacokinetics of L-arginine indicate that side effects are rare and mostly mild and dose dependent.
Klahr
Saulo
S
Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110-1092, USA. sklahr@im.wustl.edu
Morrissey
Jeremiah
J
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D011379:Prognosis; D051381:Rats; D012079:Renal Circulation / Q000502:physiology; D018570:Risk Assessment; D016896:Treatment Outcome; D015854:Up-Regulation
D009569:Nitric Oxide; D001120:Arginine