Methylarginies-induced Endothelial Dysfunction in Chronic Kidney Disease

Chronic kidney disease (CKD), defined as low glomerular filtration rates and/or the presence of albuminuria, is considered a risk factor for cardiovascular disease (CVD). In recent years, increasing emphasis has been placed on endothelial dysfunction as a key element underlying the relationship between CKD and CVD. Endothelial cells play a pivotal role in many aspects of vascular function by generating nitric oxide (NO). However, NO production is reduced in CKD patients, partially due to decreased endothelial NO production. One possible cause of NO deficiency is increased levels of endogenous NO synthase inhibitors, in particular asymmetric dimethylarginine (ADMA). Elevated plasma levels of ADMA are consequence of increased synthesis and reduced degradation. Accumulation of ADMA and inhibition of NO production might contribute to endothelial dysfunction, hypertension, initiation of atherosclerosis, and incidence of CVD. Clinical studies revealed that ADMA plasma concentration is increased in populations with renal disease, vascular diseases, and high cardiovascular risks. In this regard, ADMA is increasingly recognized as a biomarker of CKD and CVD. This review discusses ADMA-mediated endothelial dysfunction in CKD, especially focusing on the link between CKD and CVD.