The endothelial cell layer is the "guardian" of molecular traffic between the blood and surrounding tissue, and endothelial integrity plays a pivotal role in many aspects of vascular function: e.g., control of vasomotor tone and permeability. Cardiovascular risk factors such as hypertension may cause endothelial dysfunction and even disintegration, finally resulting in small vessel disappearance (vascular rarefaction) and tissue hypoxia. In patients with chronic kidney diseases (CKD), ongoing endothelial damage in the capillary system of the renal medulla and accompanying vascular rarefaction are thought to be central processes toward progressive kidney damage. In this respect, reduced nitric oxide synthesis by endothelial cells due to accumulation of endogenous inhibitors of the nitric oxide synthase such as asymmetric dimethylarginine (ADMA) has been accused of accelerating progression. Thus, reducing ADMA blood levels could be potentially beneficial in clinical trials aimed at reducing the loss of kidney function in CKD patients. Another molecule coming into the focus of cardiovascular medicine is erythropoietin (EPO). Recent experimental studies have shown that EPO - beside its effect on hematopoietic cells - protects endothelial cell function and integrity and has vasculoprotective properties. EPO could therefore prevent renal tissue injury and CKD progression due to vascular rarefaction and hypoxia.