Background and objectives Increased inflammation and oxidative stress may be caused by proteins and lipids modified by cytotoxic advanced glycation end products (AGEs) in food. Restricting food containing elevated AGEs improves these risk factors in diabeticCKD. Because diet adherence can be problematic, this study aimed to remove cytotoxic AGEs from food already ingested and to determine whether sevelamer carbonate sequesters cytotoxic AGEs in the gut, preventing their uptake and thereby reducing AGE-induced abnormalities. Design, setting, participants, &measurements This single-center, randomized, 2-month, open-label, intention-totreat, crossover study compared sevelamer carbonate with calcium carbonate treatment in stage 2-4 diabetic CKD. Participants received 2 months of treatment with one drug, had a 1-week washout, and then received the opposite drug for 2 months. Results: Sevelamer carbonate reduced HbA1c, serum methylglyoxal, serum εN-carboxymethyl-lysine, triglycerides, and 8-isoprostanes. Total cholesterol and fibroblast growth factor 23 were reduced by sevelamer carbonate, relative to calcium carbonate. AGE receptor 1 and sirtuin 1 mRNA were increased and PMNC TNFa levels were decreased by sevelamer carbonate, but not calciumcarbonate. Medications and caloric andAGE intake remained unchanged. Sevelamer carbonate reversibly bound AGE-BSA at intestinal, but not stomach, pH. Conclusions: Sevelamer carbonate significantly reducesHbA1c, fibroblast growth factor 23, lipids, andmarkers of inflammation and oxidative stress, and markedly increases antioxidantmarkers, independently of phosphorus in patients with diabetes and early kidney disease. These novel actions of sevelamer carbonate on metabolic and inflammatory abnormalities in type 2 diabetes mellitus may affect progression of early diabetic CKD.
|Original language||English (US)|
|Number of pages||9|
|Journal||Clinical Journal of the American Society of Nephrology|
|State||Published - Jun 1 2012|
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine