Concentration of dimethyl-L-arginine in the plasma of patients with end-stage renal failure

N-G N-G dimethyl-L-arginine (asymmetric dimethyl-l-arginine; ADMA) and (NN)-N-G'(G) dimethyl-L-arginine (symmetric dimethyl-L-arginine; SDMA) are naturally occurring analogues of L-arginine, the substrate for nitric oxide (NO) synthesis. ADMA is a potent inhibitor of NO synthesis, and accumulates in the plasma of patients with renal failure. However the precise concentration of ADMA and SDMA in renal patients is still controversial. This study was performed to measure plasma ADMA and SDMA concentrations by two different HPLC techniques in nine healthy controls and 10 uraemic subjects, and to investigate the effects of haemodialysis. In controls, the mean (+/- SEM) plasma concentrations of ADMA and SDMA were 0.36 +/- 0.09 and 0.39 +/- 0.05 mu mol/l respectively, yielding an ADMA/SDMA ratio of 1.2 +/- 0.17. In uraemic patients, the plasma concentrations of ADMA and SDMA were 0.9 +/- 0.08 mu mol/l (P < 0.001 compared to controls) and 3.4 +/- 0.3 mu mol/l (P < 0.001 compared to controls) with an ADMA/SDMA ratio of 0.27 +/- 0.015 (P < 0.001). In the course of one 4 h haemodialysis session, ADMA concentrations decreased from 0.99 +/- 0.13 to 0.77 +/- 0.3 mu mol/l and SDMA concentrations from 3.38 +/- 0.44 to 2.27 +/- 0.21 mu mol/l. The plasma ADMA/creatinine ratio tended to increase from 1.26 +/- 0.20 x 10(-3) to 2.01 +/- 0.41 x 10(-3). It is concluded that there is a modest (3-fold) but definite increase in plasma ADMA concentration in uraemic patients compared to controls. SDMA accumulates to a greater degree (8-fold increase) and more closely parallels creatinine concentration than ADMA. The change in the ADMA/SDMA ratio is not accounted for by greater renal or dialysis clearance of ADMA, and, even though alternative explanations are not excluded, greater metabolism of ADMA than SDMA is the most likely explanation Although small in magnitude, the increase in ADMA concentration might be biologically significant.