New pathways to renal damage: role of ADMA in retarding renal disease progression

In recent years, increasing evidence has been found that chronic kidney disease (CKD) is a strong cardiovascular risk factor, and therefore, the concept of cardiorenal association is well recognized. One possible factor that could explain this link seems to be endothelial dysfunction. It is widely recognized that endothelial dysfunction plays important roles in both the initiation and progression of atherosclerosis. In addition, we have come to understand that endothelial dysfunction may be a causative factor for proteinuria and/or progression of CKD. Asymmetric dimethylarginine (ADMA) is a naturally occurring L-arginine analogue found in plasma and various types of tissues, acting as an endogenous nitric oxide synthase inhibitor in vivo. Plasma levels of ADMA are elevated in patients with CKD and have been found to be a strong biomarker or predictor for future cardiovascular disease (CVD) as well as the progression of renal injury. These findings suggest that elevation of ADMA-mediated endothelial dysfunction may be a missing link between CVD and CKD. In this review, we discuss the biology of ADMA, especially focusing on its role in the progression of CKD.