Oral L-arginine does not improve endothelial dysfunction in children with chronic renal failure.
BACKGROUND
Cardiovascular disease is a major cause of mortality amongst patients with chronic renal failure (CRF). L-arginine has been used to improve endothelial function by increasing nitric oxide (NO) bioavailability and in animal models this in turn has attenuated the progression of atherosclerosis. We examined whether dietary L-arginine supplementation improved endothelial function in children with CRF.


METHODS
A randomized, double-blind, placebo-controlled, crossover trial of L-arginine was conducted in 21 normotensive children aged 11.5 +/- 3 (7 to 17) years with CRF (GFR 27.4 +/- 13.2 mL/min/1.73 m(2)) in whom endothelial dysfunction had previously been demonstrated. We examined the effect of L-arginineon the endothelial response to shear stress (NO-dependent) using a non-invasive technique of high-resolution ultrasound. Each subject was studied before and after 4 weeks of L-arginine (2.5 g/m(2) or 5 g/m(2) x 3/day) or placebo, separated by a rest period of 4 weeks. Brachial artery diameter was measured at rest, during increased flow (endothelial-dependent dilation) and after 25 microg of glyceryl trinitrate (endothelial-independent dilation) at each visit.


RESULTS
After oral L-arginine, plasma L-arginine levels rose from 82 +/- 20 to 179 +/- 110 micromol/L (P < 0.001). No significant change in endothelial-dependent dilation during L-arginine (7.96 +/- 2.35 to 7.71 +/- 3.22%; P> 0.05) or placebo (8.2 +/- 2.89 to 8.3 +/- 3.14%; P> 0.05) was noted. There was no change in endothelial-independent dilation.


CONCLUSIONS
Endothelial function was not improved with L-arginine, suggesting that dietary supplementation is not a useful clinical approach in children with CRF.
Bennett-Richards
Katy J
KJ
Departments of Nephrourology and Vascular Physiology, Great Ormond Street Hospital for Children NHS Trust, 34 Great Ormond Street, London WC1 3JH, England, United Kingdom. KatyJBR@aol.com
Kattenhorn
Mia
M
Donald
Ann E
AE
Oakley
Gillian R
GR
Varghese
Zac
Z
Bruckdorfer
K Richard
KR
Deanfield
John E
JE
Rees
Lesley
L
D000284:Administration, Oral; D000293:Adolescent; D001120:Arginine / Q000008:administration & dosage* / Q000097:blood; D001161:Arteriosclerosis / Q000178:diet therapy* / Q000209:etiology / Q000503:physiopathology; D002648:Child; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D009566:Nitrates / Q000097:blood; D005996:Nitroglycerin / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013314:Stress, Mechanical; D017211:Treatment Failure; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage
D009566:Nitrates; D014280:Triglycerides; D014665:Vasodilator Agents; D001120:Arginine; D005996:Nitroglycerin