Asymmetric dimethylarginine and progression of chronic kidney disease: the mild to moderate kidney disease study.
Reduced bioavailability of nitric oxide (NO) is thought to play an important role in progression of renal damage. The hypothesis that the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) is involved in progression of kidney disease was tested. Plasma ADMA concentrations and other putative progression factors were assessed in 227 relatively young patients (45.7 +/- 12.6 yr) with nondiabetic kidney diseases and mild to moderate renal failure. Progression assessed as doubling of serum creatinine and/or renal replacement therapy was evaluated prospectively. Baseline plasma ADMA concentrations in renal patients correlated significantly with serum creatinine (r = 0.595), GFR (r = -0.591), age (r = 0.281), and proteinuria (r = 0.184; all P < 0.01). Patients who reached an end point during follow-up were significantly older (P < 0.05) and had significantly higher creatinine, ADMA, and parathyroid hormone blood concentrations and protein excretion rates at baseline, whereas GFR and hemoglobin were significantly lower (all P < 0.01). Cox regression analysis revealed baseline serum creatinine (odds ratio 2.00; 95% confidence interval [CI] 1.61 to 2.49; P < 0.001) and ADMA (odds ratio 1.47; 95% CI 1.12 to 1.93 for an increment of 0.1 mumol/L; P < 0.006) as independent predictors of disease progression. In patients with ADMA levels above median, progression was significantly faster (P < 0.0001), and their mean follow-up time to a progression end point was 52.8 mo (95% CI 46.9 to 58.8) as compared with 71.6 mo (95% CI 66.2 to 76.9) in patients with ADMA levels below the median. The endogenous NO synthase inhibitor ADMA is significantly associated with progression of nondiabetic kidney diseases. Lowering plasma ADMA concentrations may be a novel therapeutic target to prevent progressive renal impairment.
Fliser
Danilo
D
Division of Nephrology, Department of Internal Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. filser.danilo@mh-hannover.de
Kronenberg
Florian
F
Kielstein
Jan T
JT
Morath
Christian
C
Bode-Böger
Stefanie M
SM
Haller
Hermann
H
Ritz
Eberhard
E
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood; D016016:Proportional Hazards Models; D051437:Renal Insufficiency / Q000473:pathology; D016896:Treatment Outcome
D006454:Hemoglobins; D010281:Parathyroid Hormone; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D003404:Creatinine