L. De Nicola et al., Randomized, double-blind, placebo-controlled study of arginine supplementation in chronic renal failure, KIDNEY INT, 56(2), 1999, pp. 674-684
Background Supplementation with L-arginine (ARG) strikingly ameliorates pro
teinuria and glomerulosclerosis in remnant rats by overcoming nitric oxide
(NO) deficiency. Whether or not the same holds true in humans is unknown. T
his 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 N
O synthesis), and urinary cGMP (an intracellular mediator of NO), as well a
s proteinuria and renal functional reserve (RFR) in CRF patients orally tre
ated 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 b
asal comparisons.
Results. In CRF patients at baseline, plasma arginine was within the normal
range; similarly, the urinary excretion of NO, was comparable to the NOR v
alue (CRF, 0.440 +/- 0.02; NOR, 0.537 +/- 0.08 mu mol/min, P = NS). The pla
sma NO3 levels were higher than in NOR (CRF, 74 +/- 6; NOR, 27 +/- 2 mu mol
/liter, P < 0.001), and consequently the renal clearance of NO, resulted as
being reduced. During the six months of treatment, although a remarkable s
teadiness 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. T
his 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 pre
ssure, proteinuria, glomerular filtration rate, and renal plasma flow did n
ot vary. Likewise, RFR, which was reduced at baseline in CRF, did not impro
ve after ARG.
Conclusions. In moderate CRF, the tonic release of NO is constant and, like
ly, not impaired, and ARG supplementation does not lead to an enhancement o
f NO activity, thus resulting in no renal effect.