Impaired vascular function in patients with chronic kidney disease who have elevated symmetric dimethylarginine but not asymmetric dimethylarginine

Abstract

Chronic kidney disease (CKD) is associated with heightened cardiovascular disease (CVD) risk, partly due to impaired peripheral vascular function. Symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) are emerging biomarkers implicated in nitric oxide (NO) regulation and vascular health. Although ADMA is a well-established inhibitor of NO synthesis, recent evidence suggests that SDMA may also play a critical role in vascular health, especially in CKD before end-stage. Thus, in 23 stages 3 and 4 patients with CKD (66 ± 9 yr) and 32 age-matched controls (64 ± 8 yr), we compared serum SDMA and ADMA levels and examined their associations with vascular function, including flow-mediated dilation (FMD), peak blood velocity to reactive hyperemia, and carotid-femoral pulse wave velocity (cfPWV). SDMA was significantly elevated in patients with CKD (163 ± 37 vs. 100 ± 15 ng/mL, P < 0.0001), while ADMA did not differ significantly between groups (111 ± 22 vs. 103 ± 12 ng/mL, P = 0.083). Patients with CKD had lower FMD (3.66 ± 2.45 vs. 4.47 ± 2.45%, P = 0.048) and peak blood velocity (47.43 ± 16.67 vs. 60.18 ± 16.88 cm/s, P = 0.009), but higher cfPWV (8.82 ± 1.53 vs. 7.69 ± 1.35 m/s, P = 0.004) than controls. Pooled analysis revealed that SDMA correlated inversely with eGFR (r = ―0.86, P < 0.0001), FMD (rs = ―0.28, P = 0.039), and peak blood velocity (rs = ―0.40, P = 0.001) but not cfPWV (r = 0.14, P = 0.338). ADMA correlated inversely with peak blood velocity (rs = ―0.28, P = 0.042) but not eGFR (r = ―0.25, P = 0.063), FMD (rs = ―0.06, P = 0.664), or cfPWV (r = 0.21, P = 0.146). Collectively, these findings suggest that SDMA, relative to ADMA, may be a stronger marker of vascular dysfunction in stages 3 and 4 CKD. However, the predictive value of SDMA for vascular function was modest, which may limit its overall potential as a biomarker for vascular function in CKD.