Increased plasma nitric oxide, L-arginine, and arginase-1 in cirrhotic patients with progressive renal dysfunction.
OBJECTIVE
Increased levels of nitric oxide (NO) are hypothesized to contribute to renal dysfunction in patients with decompensated cirrhosis. In this study, we examined whether splanchnic and/or peripheral NO levels and L-arginine (L-Arg) correlate with progressive renal dysfunction in cirrhotics.


METHODS
Serum NO metabolites (NOx) and L-Arg were measured in: controls (n = 10); organ donors (n = 12); compensated cirrhotics (n = 17), cirrhotics with ascites (n = 25), refractory ascites (n = 11) or hepatorenal syndrome type II (HRS) (n = 11) and chronic renal failure patients (n = 18).


RESULTS
Plasma NOx and L-Arg levels rose progressively with worsening renal function in decompensated cirrhotics. Both NOx and L-Arg levels were highest in patients with HRS (P < 0.001 and P < 0.025, respectively). While there were no differences in NOx levels related to the site of sampling, L-Arg levels were lowest in hepatic venous blood. There were significant relationships of NOx and L-Arg with Model for End-Stage Liver Disease score and Child-Pugh scores (P < 0.04 and P < 0.01, respectively). Multivariate analysis showed a significant relationship between NOx, L-Arg and HRS.


CONCLUSIONS
Worsening renal function in decompensated cirrhosis is accompanied by progressive elevation in plasma NOx and L-Arg. These findings support the hypothesis that NO-mediated vasodilation is probably linked with the mechanism of progressive renal failure in decompensated cirrhotics.
Kayali
Zeid
Z
Transplantation Institute, Loma Linda University Medical Center and Loma Linda University School of Medicine, Loma Linda, California 92354, USA. zkayali@llu.edu
Herring
Jason
J
Baron
Pedro
P
Franco
Edson
E
Ojogho
Okechukwu
O
Smith
Jason
J
Watkins
Gregory
G
Smith
Douglas
D
Lamin
Victor
V
Hoang
Thanh
T
Sharma
Rajiv
R
Mathahs
Meleah
M
Sowers
Lawrance
L
Brown
Kyle E
KE
Schmidt
Warren N
WN
D000328:Adult; D001119:Arginase / Q000097:blood*; D001120:Arginine / Q000097:blood*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018450:Disease Progression; D005260:Female; D006530:Hepatorenal Syndrome / Q000097:blood*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D011446:Prospective Studies; D018709:Statistics, Nonparametric
D009569:Nitric Oxide; D001120:Arginine; D001119:Arginase