title: Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products in diabetic kidney disease.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 (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.
  
  
  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.
authors.affiliation: Division of Experimental Diabetes and Aging, Department of Geriatrics, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Vlassara
authors.forename: Jaime
authors.initials: J
authors.lastname: Uribarri
authors.forename: Weijing
authors.initials: W
authors.lastname: Cai
authors.forename: Susan
authors.initials: S
authors.lastname: Goodman
authors.forename: Renata
authors.initials: R
authors.lastname: Pyzik
authors.forename: James
authors.initials: J
authors.lastname: Post
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Grosjean
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.forename: Gary E
authors.initials: GE
authors.lastname: Striker
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000097:blood; D002119:Calcium Carbonate / Q000627:therapeutic use*; D002614:Chelating Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009519:New York City; D018384:Oxidative Stress / Q000187:drug effects; D010758:Phosphorus / Q000097:blood; D011073:Polyamines / Q000627:therapeutic use*; D000069603:Sevelamer; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002118:Calcium; D002119:Calcium Carbonate; D002614:Chelating Agents; D015237:Dinoprost; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D018836:Inflammation Mediators; D008055:Lipids; D010758:Phosphorus; D011073:Polyamines; D000069603:Sevelamer; C517652:hemoglobin A1c protein, human; C075750:8-epi-prostaglandin F2alpha