Randomized, double-blind, placebo-controlled study of arginine supplementation in chronic renal failure.
BACKGROUND
Supplementation with L-arginine (ARG) strikingly ameliorates proteinuria and glomerulosclerosis in remnant rats by overcoming nitric oxide (NO) deficiency. Whether or not the same holds true in humans is unknown. This study aimed at evaluating the effects of ARG on the NO system and renal function in proteinuric patients with moderate chronic renal failure (CRF).


METHODS
We measured plasma arginine, urinary and plasma NO3 (an index of NO synthesis), and urinary cGMP (an intracellular mediator of NO), as well as proteinuria and renal functional reserve (RFR) in CRF patients orally treated for six months with either ARG (0.2 g/kg body wt/day, CRF-A group) or the control vehicle (CRF-C). Normal subjects (NOR) were also included for basal comparisons.


RESULTS
In CRF patients at baseline, plasma arginine was within the normal range; similarly, the urinary excretion of NO3 was comparable to the NOR value (CRF, 0. 440 +/- 0.02; NOR, 0.537 +/- 0.08 micromol/min, P = NS). The plasma NO3 levels were higher than in NOR (CRF, 74 +/- 6; NOR, 27 +/- 2 micromol/liter, P < 0.001), and consequently the renal clearance of NO3 resulted as being reduced. During the six months of treatment, although a remarkable steadiness of ARG and NO3 levels was detected in the CRF-C group, the CRF-A group was characterized by a marked and immediate increase of plasma ARG. This was associated, however, with a delayed increment in urinary and plasma NO3 levels and no change in urinary cGMP. In CRF-A, as in CRF-C, blood pressure, proteinuria, glomerular filtration rate, and renal plasma flow did not vary. Likewise, RFR, which was reduced at baseline in CRF, did not improve after ARG.


CONCLUSIONS
In moderate CRF, the tonic release of NO is constant and, likely, not impaired, and ARG supplementation does not lead to an enhancement of NO activity, thus resulting in no renal effect.
De Nicola
L
L
Nephrology Division and Department of Biochemistry, School of Medicine, University Federico II of Naples, Italy.
Bellizzi
V
V
Minutolo
R
R
Andreucci
M
M
Capuano
A
A
Garibotto
G
G
Corso
G
G
Andreucci
V E
VE
Cianciaruso
B
B
D000293:Adolescent; D000328:Adult; D000596:Amino Acids / Q000378:metabolism; D001120:Arginine / Q000008:administration & dosage* / Q000097:blood; D006152:Cyclic GMP / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism; D010919:Placebos; D011507:Proteinuria / Q000378:metabolism; D012079:Renal Circulation / Q000502:physiology
D000596:Amino Acids; D009566:Nitrates; D010919:Placebos; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP