Asymmetric dimethylarginine and mortality in stages 3 to 4 chronic kidney disease.
OBJECTIVE
Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, reduces bioavailability of nitric oxide and induces endothelial dysfunction. This dimethylated amino acid accumulates in chronic kidney disease and may be involved in the pathophysiology of cardiovascular disease (CVD) in this population.


METHODS
The Modification of Diet in Renal Disease Study was a randomized, controlled trial conducted between 1989 and 1993. We measured ADMA in frozen samples collected at baseline (n = 820) and obtained survival status, up to December 31, 2000, from the National Death Index. We examined the relationship of ADMA with prevalent CVD and performed multivariable Cox models to examine the relationship of ADMA with all-cause and CVD mortality.


RESULTS
Mean (SD) age was 52 (12) yr, GFR was 32 +/- 12 ml/min per 1.73 m(2), and ADMA was 0.70 +/- 0.25 micromol/L. A 1-SD increase in ADMA was associated with a 31% increased odds of prevalent CVD in an adjusted logistic regression model. During the 10-yr follow-up period, 202 (25%) participants died of any cause, 122 (15%) from CVD, and 545 (66%) reached kidney failure. In multivariable Cox models, a 1-SD increase in ADMA was associated with a 9% increased risk for all-cause and 19% increased risk for CVD mortality.


CONCLUSIONS
In this cohort of patients with predominantly nondiabetic, stages 3 to 4 chronic kidney disease, there was a strong association of ADMA with prevalent CVD and a modest association with all-cause and CVD mortality.
Young
Jill Melendez
JM
Department of Medicine, Division of Nephrology, Tufts Medical Center, Boston, Massachusetts, USA.
Terrin
Norma
N
Wang
Xuelei
X
Greene
Tom
T
Beck
Gerald J
GJ
Kusek
John W
JW
Collins
Allan J
AJ
Sarnak
Mark J
MJ
Menon
Vandana
V
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009569:Nitric Oxide / Q000378:metabolism; D015995:Prevalence; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000401:mortality*; D012307:Risk Factors; D012720:Severity of Illness Index
D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine