Markers and possible uremic toxins: Japanese experiences

Oxidative stress and resultant accumulation of advanced glycation end products (AGEs) are closely related to the development of cardiovascular disease, which is the major cause of death among end-stage renal disease patients. Several markers of oxidative stress, such as malondialdehyde, oxidized low-density lipoprotein, AGEs and 8-hydroxyde-oxyguanosine, are significantly elevated in circulating blood and/or tissue levels. Vitamin E is one of the scavengers opposed to oxidative stress and has been bonded to the dialyzer membrane surface to suppress oxidative stress related to hemodialysis itself. Vitamin E-coated dialyzers are widely used in Japan and several favorable clinical effects have been reported. Improved biocompatibility leads to decreased activation of circulating blood cells and these are related to reduced doses of heparin, improvement of anemia, and dose reduction in erythropoiesis-stimulating agents. Improvement of the cytokine network and immunological system is also suggested. It is expected that regression of atherosclerosis and slowed vascular calcification might occur parallel with reduction of oxidative stress by vitamin E-coated dialyzer. An improvement of endothelial function and dialysis hypotension during dialysis has also been reported. In small studies in Japan, improvement of nutritional state, insulin resistance and quality of life have been suggested. Although a larger scale control study will be needed, hemodialysis with vitamin E-coated membrane might become another powerful treatment modality other than hemodiafiltration.