The angiopoietin/Tie-2 axis: a novel player in chronic kidney disease

The development of atherosclerosis in patients with chronic kidney disease (CKD) is severely accelerated leading to life-threatening cardiovascular (CV) events and its pathogenesis is different from that in the general population. Mainly the so-called uremic toxins are thought to count responsible for this phenomenon. Recently, the angiopoietin/Tie2 system has been identified as a potential new player in the uremia-associated pathogenesis of atherosclerosis. This review provides an overview of molecular mechanisms of angiopoietin-1/-2 and Tie2 signaling in regard to the endothelial activation status in health and disease. The first part reviews the role of angiopoietins in experimental models of inflammation. Then, we summarize the most important clinical trials showing a severely altered angiopoietin balance in favor of Ang-2. Those trials contain data on patients with CKD stage 1-4, on dialysis (CKD stage 5), arterial hypertension, and diabetes mellitus. Future experiments to prove a direct mechanism by which angiopoietins accelerate and/or aggravate atherosclerotic burden in CKD patients are highly desirable. Very recently, a clinical trial (in oncology) proved safety of a selective angiopoietin inhibitor. Those latest drugs might represent a future treatment option against CKD-associated micro-inflammation.