Inflammation and oxidative stress in ESRD--the role of myeloperoxidase

It has been increasingly apparent that end-stage renal disease (ESRD) patients carry an inflammatory burden, which may play a pivotal role in the evolution of not only wasting but also of the massive increase in the relative risk of cardiovascular disease (CVD). Also increased oxidative stress (an impairment of the pro- and antioxidant redox balance) is a common feature of ESRD, and it has been speculated that it is interrelated to inflammation. Myeloperoxidase (MPO) is a hemoprotein secreted during activation of neutrophils, which plays an important role in the defense of the organism by catalyzing the production of hypochloric acid (HOCl). MPO has been speculated to be a major oxidative stress pathway in ESRD. Emerging evidence suggests that enhanced MPO-activity, via increased generation of diffusible oxidants and consumption of nitric oxide, may be an important risk factor for vascular disease. Indeed, MPO serum levels are a powerful predictor of cardiovascular events in non-renal patients. As a functional polymorphism (SNP) has been identified at position -463 (where the A allele is associated with lower MPO expression) this sequence of event may be affected by genetic factors. Nutritional and pharmacological antioxidant strategies that interfere with chlorinated MPO-associated oxidative stress pathways need to be investigated in the ESRD patient population.