TY - JOUR
AU - Vlassara H.
AU - Striker G.
AU - Woodward Mark
AU - Yubero-Serrano E.
AU - Poretsky L.
AB - <p>
BACKGROUND AND OBJECTIVES: The primary goals were to re-examine whether sevelamer carbonate (SC) reduces advanced glycation end products (AGEs) (methylglyoxal and carboxymethyllysine [CML]), increases antioxidant defenses, reduces pro-oxidants, and improves hemoglobin A1c (HbA1c) in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Secondary goals examined albuminuria, age, race, sex, and metformin prescription. DESIGN, SETTING, PARTICIPANTS, &amp; MEASUREMENTS: This two-center, randomized, intention-to-treat, open-label study evaluated 117 patients with T2DM (HbA1c &gt;6.5%) and stages 2-4 DKD (urinary albumin/creatinine ratio &gt;/=200 mg/g) treated with SC (1600 mg) or calcium carbonate (1200 mg), three times a day, without changing medications or diet. Statistical analyses used linear mixed models adjusted for randomization levels. Preselected subgroup analyses of sex, race, age, and metformin were conducted. RESULTS: SC lowered serum methylglyoxal (95% confidence interval [CI], -0.72 to -0.29; P&lt;0.001), serum CML (95% CI, -5.08 to -1.35; P<!--=0.001), and intracellular CML (95% CI, -1.63 to -0.28; P=0.01). SC increased anti-inflammatory defenses, including nuclear factor like-2 (95% CI, 0.58 to 1.29; P=0.001), AGE receptor 1 (95% CI, 0.23 to 0.96; P=0.001), NAD-dependent deacetylase sirtuin-1 (95% CI, 0.20 to 0.86; P=0.002), and estrogen receptor alpha (95% CI, 1.38 to 2.73; P </=0.001). SC also decreased proinflammatory factors such as TNF receptor 1 (95% CI, -1.56 to -0.72; P</=0.001) and the receptor for AGEs (95% CI, -0.58 to 1.53; P</=0.001). There were no differences in HbA1c, GFR, or albuminuria in the overall group. Subanalyses showed that SC lowered HbA1c in women (95% CI, -1.71 to -0.27; P=0.01, interaction P=0.002), and reduced albuminuria in those aged <65 years (95% CI, -1.15 to -0.07; P=0.03, interaction P=0.02) and non-Caucasians (95% CI, -1.11 to -0.22; P=0.003, interaction P</=0.001), whereas albuminuria increased after SC and calcium carbonate in Caucasians. CONCLUSIONS: SC reduced circulating and cellular AGEs, increased antioxidants, and decreased pro-oxidants, but did not change HbA1c or the albumin/creatinine ratio overall in patients with T2DM and DKD. Because subanalyses revealed that SC may reduce HbA1c and albuminuria in some patients with T2DM with DKD, further studies may be warranted.-->
</p>

AD - Lipid and Atherosclerosis Unit/IMIBIC/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain and CIBER Fisiopatholigia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain;<br/>The George Institute for Global Health, University of Oxford, Oxford, United Kingdom; University of Sydney, Sydney, New South Wales, Australia;<br/>Divisions of Endocrinology and Nephrology, Department of Medicine, and.<br/>Division of Experimental Diabetes and Aging, Department of Geriatrics, Divisions of Icahn School of Medicine at Mount Sinai, New York, New York; and Divisions of Endocrinology and.<br/>Division of Experimental Diabetes and Aging, Department of Geriatrics, Divisions of Icahn School of Medicine at Mount Sinai, New York, New York; and Nephrology, Department of Medicine, and Mount Sinai Health System, New York, New York gary.striker@mssm.edu.
AN - 25710801
BT - Clinical Journal of the American Society of Nephrology
DA - -45572182451
DP - NLM
ET - 2015/02/25
LA - Eng
LB - PDO<br/>UK
M1 - 5
N1 - Yubero-Serrano, Elena M<br/>Woodward, Mark<br/>Poretsky, Leonid<br/>Vlassara, Helen<br/>Striker, Gary E<br/>on behalf of AGE-less Study Group<br/>Clin J Am Soc Nephrol. 2015 Feb 20. pii: CJN.07750814.
N2 - <p>
BACKGROUND AND OBJECTIVES: The primary goals were to re-examine whether sevelamer carbonate (SC) reduces advanced glycation end products (AGEs) (methylglyoxal and carboxymethyllysine [CML]), increases antioxidant defenses, reduces pro-oxidants, and improves hemoglobin A1c (HbA1c) in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Secondary goals examined albuminuria, age, race, sex, and metformin prescription. DESIGN, SETTING, PARTICIPANTS, &amp; MEASUREMENTS: This two-center, randomized, intention-to-treat, open-label study evaluated 117 patients with T2DM (HbA1c &gt;6.5%) and stages 2-4 DKD (urinary albumin/creatinine ratio &gt;/=200 mg/g) treated with SC (1600 mg) or calcium carbonate (1200 mg), three times a day, without changing medications or diet. Statistical analyses used linear mixed models adjusted for randomization levels. Preselected subgroup analyses of sex, race, age, and metformin were conducted. RESULTS: SC lowered serum methylglyoxal (95% confidence interval [CI], -0.72 to -0.29; P&lt;0.001), serum CML (95% CI, -5.08 to -1.35; P<!--=0.001), and intracellular CML (95% CI, -1.63 to -0.28; P=0.01). SC increased anti-inflammatory defenses, including nuclear factor like-2 (95% CI, 0.58 to 1.29; P=0.001), AGE receptor 1 (95% CI, 0.23 to 0.96; P=0.001), NAD-dependent deacetylase sirtuin-1 (95% CI, 0.20 to 0.86; P=0.002), and estrogen receptor alpha (95% CI, 1.38 to 2.73; P </=0.001). SC also decreased proinflammatory factors such as TNF receptor 1 (95% CI, -1.56 to -0.72; P</=0.001) and the receptor for AGEs (95% CI, -0.58 to 1.53; P</=0.001). There were no differences in HbA1c, GFR, or albuminuria in the overall group. Subanalyses showed that SC lowered HbA1c in women (95% CI, -1.71 to -0.27; P=0.01, interaction P=0.002), and reduced albuminuria in those aged <65 years (95% CI, -1.15 to -0.07; P=0.03, interaction P=0.02) and non-Caucasians (95% CI, -1.11 to -0.22; P=0.003, interaction P</=0.001), whereas albuminuria increased after SC and calcium carbonate in Caucasians. CONCLUSIONS: SC reduced circulating and cellular AGEs, increased antioxidants, and decreased pro-oxidants, but did not change HbA1c or the albumin/creatinine ratio overall in patients with T2DM and DKD. Because subanalyses revealed that SC may reduce HbA1c and albuminuria in some patients with T2DM with DKD, further studies may be warranted.-->
</p>

PY - 2015
SN - 1555-905X (Electronic)<br/>1555-9041 (Linking)
SP - 759
EP - 66
T2 - Clinical Journal of the American Society of Nephrology
TI - Effects of Sevelamer Carbonate on Advanced Glycation End Products and Antioxidant/Pro-Oxidant Status in Patients with Diabetic Kidney Disease
VL - 10
ER -