Vlassara H, Uribarri J, Cai W, et al.
Clin J Am Soc Nephrol. 2012 Mar 29. (Original)
PMID: 22461535
Background
and objectivesIncreased 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, & measurementsThis 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.ResultsSevelamer 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.ConclusionsSevelamer 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.
No comments:
Post a Comment