This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator. The incidence and prevalence of chronic kidney disease (CKD) is increasing at a rapid rate. Cardiovascular disease (CVD) is the leading cause of death in this patient population. The high rate of CVD in patients with CKD is not completely explained by traditional risk factors and mortality remains high despite management of these risk factors. Recently, attention has been shifted to non-traditional risk factors such as inflammation, oxidative stress, glycation, and associated endothelial dysfunction as potential contributors to the high rate of CVD in the CKD population. Advanced glycation end products (AGE) are a heterogeneous group of compounds formed in the body from the non-enzymatic glycation of proteins, lipids, and nucleic acids. AGE then can interact with specific receptors and ultimately generate mediators of inflammation and oxidation. AGE are known to be elevated in CKD. There is evidence in vitro, as well as in vivo in animal models, that AGE play a role in the pathogenesis of CVD by physically altering the structure and function of arterial walls and promoting oxidative stress and inflammation through the release of various cytokines. While endogenous production of AGE were thought to be the main contributor to the circulating AGE pool, recent evidence suggests that dietary intake of AGE is also an important contributor. Recent data also shows that dietary intake of AGE correlates with serum AGE levels, levels of certain inflammatory cytokines, and with markers of oxidative stress and endothelial dysfunction. Moreover, preliminary studies reducing dietary AGE intake have demonstrated a significant effect on reducing circulating AGE levels. It remains to be demonstrated whether this dietary intervention also modifies surrogate markers of vascular/endothelial function such as arterial stiffness and/or vascular dilatation in response to ischemia. The purpose of this study is to determine the effect of a low AGE diet on serum AGE levels, markers of inflammation, oxidative stress, and endothelial dysfunction, as well as non-invasive measurements of vascular function in non-diabetic patients with CKD. Hypothesis: Dietary advanced glycoxidation end products (AGE) play an important role in the increased inflammatory state in chronic kidney disease (CKD) and contribute to the high rate of cardiovascular disease (CVD) found in this patient population.
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