Division of Experimental Diabetes and Aging, Department of Geriatrics, Mount Sinai School of Medicine, New York, New York, USA.
Clin J Am Soc Nephrol. 2012 Jun;7(6):934-42. doi: 10.2215/CJN.12891211. Epub 2012 Mar 29.
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.
Sevelamer carbonate reduced HbA1c, serum methylglyoxal, serum (ε)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 TNFα 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.
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.
食物中细胞毒性的晚期糖基化终产物（AGE）修饰的蛋白质和脂质可能导致炎症和氧化应激增加。限制富含 AGE 的食物可改善糖尿病 CKD 患者的这些危险因素。由于饮食依从性可能存在问题，本研究旨在从已摄入的食物中去除细胞毒性 AGE，并确定是否碳酸司维拉姆可在肠道中螯合细胞毒性 AGE，从而防止其吸收，从而减少 AGE 诱导的异常。
设计、地点、参与者和测量：这是一项单中心、随机、2 个月、开放标签、意向治疗、交叉研究，比较了碳酸司维拉姆与碳酸钙治疗 2-4 期糖尿病 CKD 的疗效。参与者接受了 2 个月的一种药物治疗，然后进行了 1 周的洗脱期，再接受了 2 个月的另一种药物治疗。
碳酸司维拉姆降低了 HbA1c、血清甲基乙二醛、血清（ε）N-羧甲基赖氨酸、甘油三酯和 8-异前列腺素。与碳酸钙相比，碳酸司维拉姆降低了总胆固醇和成纤维细胞生长因子 23。碳酸司维拉姆增加了 AGE 受体 1 和 Sirtuin 1 mRNA，降低了 PMNC TNFα水平，但碳酸钙没有。药物、热量和 AGE 摄入保持不变。碳酸司维拉姆在肠道 pH 值而不是胃 pH 值下可逆地结合 AGE-BSA。
碳酸司维拉姆可显著降低糖尿病和早期肾病患者的 HbA1c、成纤维细胞生长因子 23、脂质和炎症及氧化应激标志物，同时显著增加抗氧化标志物，独立于磷。碳酸司维拉姆在 2 型糖尿病代谢和炎症异常方面的这些新作用可能影响早期糖尿病 CKD 的进展。
