Asymmetric dimethylarginine and clinical outcomes in chronic kidney disease

Background and objectives: Elevated plasma level of asymmetric dimethylarginine (ADMA) have been reported to be associated with endothelial dysfunction and atherosclerosis risk factors, and may predict cardiovascular events in patients with ESRD. In this study, we aimed to assess the association between plasma ADMA and long-term outcome in a cohort of patients with stage 3 to 4 chronic kidney disease (CKD). Design, setting, participants, & measurements: From July 2006 to June 2009, 298 consecutive patients with stage 3 to 4 CKD scheduled to undergo coronary angiography were recruited. Plasma ADMA levels were determined using HPLC. Results: The mean age was 73 ± 10 years. Approximately half of the patients had diabetes and 88 patients had proteinuria. The baseline estimated GFR (eGFR) was 44 ± 13 ml/min per 1.73 m². The plasma ADMA levels of the patients with proteinuria were significantly higher than those without. The plasma ADMA levels correlated significantly with eGFR. During the median follow-up period of 2.7 years, we observed 26 all-cause deaths, 12 nonfatal myocardial infarctions, and 2 strokes. Multivariate Cox analysis revealed that an increase of 0.1 μmol/L in plasma ADMA level was associated with a 37% increased risk of the composite outcomes of all-cause deaths, nonfatal myocardial infarctions, and strokes. Conclusions: In this elder and high-risk population with stage 3 to 4 CKD, high plasma ADMA level was associated with low eGFR and macroalbuminuria. Furthermore, high plasma ADMA level appeared to be an independent predictor of long-term outcome.