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 diabetic CKD. 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-to-treat, 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 (epsilon)N-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 TNFalpha levels were decreased by sevelamer carbonate, but not calcium carbonate. Medications and caloric and AGE intake remained unchanged. Sevelamer carbonate reversibly bound AGE-BSA at intestinal, but not stomach, pH. CONCLUSIONS: Sevelamer carbonate significantly reduces HbA1c, fibroblast growth factor 23, lipids, and markers of inflammation and oxidative stress, and markedly increases antioxidant markers, 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.
AD - Division of Experimental Diabetes and Aging, Department of Geriatrics, Mount Sinai School of Medicine, New York, New York;, daggerDivision of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, New York;, double daggerBronx Veterans Administration Hospital, Bronx, New York;, section signDivision of Nephrology, Department of Medicine, Pavia, Italy, ||George Institute, University of Sydney, Sydney, Australia. AN - 22461535 BT - Clinical Journal of the American Society of Nephrology C2 - 3362316 DA - -35726387164 DP - NLM ET - 2012/03/31 LA - eng M1 - 6 N1 - Vlassara, HelenUribarri, JaimeCai, WeijingGoodman, SusanPyzik, RenataPost, JamesGrosjean, FabrizioWoodward, MarkStriker, Gary ER01 DK091231/DK/NIDDK NIH HHS/United StatesUnited StatesClin J Am Soc Nephrol. 2012 Jun;7(6):934-42. Epub 2012 Mar 29. N2 -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 diabetic CKD. 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-to-treat, 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 (epsilon)N-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 TNFalpha levels were decreased by sevelamer carbonate, but not calcium carbonate. Medications and caloric and AGE intake remained unchanged. Sevelamer carbonate reversibly bound AGE-BSA at intestinal, but not stomach, pH. CONCLUSIONS: Sevelamer carbonate significantly reduces HbA1c, fibroblast growth factor 23, lipids, and markers of inflammation and oxidative stress, and markedly increases antioxidant markers, 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.
PY - 2012 SN - 1555-905X (Electronic)1555-9041 (Linking) SP - 934 EP - 42 T2 - Clinical Journal of the American Society of Nephrology TI - Effects of Sevelamer on HbA1c, Inflammation, and Advanced Glycation End Products in Diabetic Kidney Disease VL - 7 ER -