The endothelium as a target in renal diseases

The endothelium is a fundamental layer in the arterial wall both for the local regulation of flow to critical organs like the heart, brain and kidney, and for the protection of the vascular system from atherogenic insults. Inhibition of nitric oxide (NO) synthesis has profound effects at systemic and renal levels. Low NO bioavailability may occur in essential hypertension and in a variety of conditions associated with high cardiovascular risk. High oxidative stress and low availability of the substrate of NO-synthase, l-arginine, as well as an increase of endogenous NO inhibitors such as asymmetric dimethylarginine (ADMA) may engender endothelial dysfunction. This alteration is very frequent in patients with chronic kidney disease (CKD) and may contribute to accelerated progression of CKD, hypertension and cardiovascular complications. The kidney not only reabsorbs but also synthesizes l-arginine and appears to be a central organ for the catabolism of ADMA, mainly because it is richly endowed with the enzyme that degrades ADMA, dimethylarginine dimethylaminohydrolase (DDAH). Recent studies demonstrated that ADMA accumulation predicts both progression to end-stage renal disease and death in patients with CKD, again further suggesting that ADMA is a potentially important treatment target in clinical trials aimed at reducing the rate of loss of renal function in these patients.