03 June 2014
Background/Aims: Asymmetric dimethylarginine (ADMA) is a prognostic factor in patients with chronic kidney disease (CKD). However, the relationships among factors influencing the metabolism of ADMA and the CKD progression are not fully understood. Methods: Serum ADMA, and variables related to the metabolism of ADMA were measured in 181 non-dialysis patients (CKD stages 3-5) and in 46 controls. Patients were assessed at baseline, and 6 and 12 months after the initiation of the study. Results: Patients had increased baseline ADMA, advanced glycation end products (AGE), and advanced oxidation protein products (AOPP) compared with controls (P<0.001). In a total of 164 patients who completed a one-year study, the estimated GFR (eGFR) declined from 23.5 (17.7-36) mL/min/1.73m<sup>2</sup> to 21 (14.7-31.5) (P=0.018), AGE rose from 1.58 (1.38-1.90) μmol/L to 1.76 (1.52-2.21) (P<0.001), while ADMA, AOPP, tubular function, and proteinuria remained stable. In a multiple regression model (adjusted R<sup>2</sup> = 0.49, P<0.0001), the interaction of relatively higher baseline eGFR, i.e. > 25 mL/min/1.73m<sup>2</sup>, with higher ADMA (P=0.02) and higher AOPP (P=0.04) predicted the severest decrease in eGFR per year. Other predictors of progression were higher baseline AGE (P<0.001), proteinuria (P=0.003), hypertension (P=0.01), and higher baseline eGFR (P=0.03). Conclusion: Elevated ADMA and markers of oxidative stress were strong predictors of progression in patients with eGFR between 25-40 mL/min/1.73m<sup>2</sup> , i.e. at the borderline of CKD stages 3-4.