Effects of sevelamer carbonate on advanced glycation end products and antioxidant/pro-oxidant status in patients with diabetic kidney disease

Elena M. Yubero-Serrano, Mark Woodward, Leonid Poretsky, Helen Vlassara, Gary E. Striker, Study Group Age-Less Study Group, Leonid Poretsky, Helen Vlassara, Gary E. Striker, Agustin Busta, Nikolas B. Harbord, Kobena Dadzie, Julie Islam, Usman Ali, Ronald Tamler, Grishma Parikh, Eliot Rayfield, Luba Rakhlin, Jaime Uribarri, Rebecca KentKamala Mantha-Thaler, Lynn Polmanteer, Megan Fendt, Anita Kalaj, Elizabeth McKee, Elizabeth Tripp, Renata A. Pyzik, Lauren Tirri, Johanna F. Kruckelmann, Shobha M. Swamy, Xue Chen, Weijing Cai, Sharon J. Elliot

Research output: Contribution to journalArticle

Abstract

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, & measurements This two-center, randomized, intention-to-treat, open-label study evaluated 117 patients with T2DM(HbA1c.6.5%) and stages 2–4 DKD (urinary albumin/creatinine ratio $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], 20.72 to 20.29; P,0.001), serum CML (95% CI, 25.08 to 21.35; P≤0.001), and intracellular CML (95% CI, 21.63 to 20.28; 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 a (95% CI, 1.38 to 2.73; P ≤0.001). SC also decreased proinflammatory factors such as TNF receptor 1 (95% CI, 21.56 to 20.72; P≤0.001) and the receptor for AGEs (95% CI, 20.58 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, 21.71 to 20.27; P=0.01, interaction P=0.002), and reduced albuminuria in those aged,65 years (95% CI, 21.15 to 20.07; P=0.03, interaction P=0.02) and non-Caucasians (95% CI, 21.11 to 20.22; 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.

Original languageEnglish (US)
Pages (from-to)759-766
Number of pages8
JournalClinical Journal of the American Society of Nephrology
Volume10
Issue number5
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Advanced Glycosylation End Products
Diabetic Nephropathies
Reactive Oxygen Species
Antioxidants
Confidence Intervals
Albuminuria
Hemoglobins
Type 2 Diabetes Mellitus
Pyruvaldehyde
Calcium Carbonate
Metformin
Sevelamer
Albumins
Creatinine
Sirtuin 1
Tumor Necrosis Factor Receptors
Random Allocation
Serum
Estrogen Receptors
NAD

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

Cite this

Yubero-Serrano, E. M., Woodward, M., Poretsky, L., Vlassara, H., Striker, G. E., Age-Less Study Group, S. G., ... Elliot, S. J. (2015). Effects of sevelamer carbonate on advanced glycation end products and antioxidant/pro-oxidant status in patients with diabetic kidney disease. Clinical Journal of the American Society of Nephrology, 10(5), 759-766. https://doi.org/10.2215/CJN.07750814

Effects of sevelamer carbonate on advanced glycation end products and antioxidant/pro-oxidant status in patients with diabetic kidney disease. / Yubero-Serrano, Elena M.; Woodward, Mark; Poretsky, Leonid; Vlassara, Helen; Striker, Gary E.; Age-Less Study Group, Study Group; Poretsky, Leonid; Vlassara, Helen; Striker, Gary E.; Busta, Agustin; Harbord, Nikolas B.; Dadzie, Kobena; Islam, Julie; Ali, Usman; Tamler, Ronald; Parikh, Grishma; Rayfield, Eliot; Rakhlin, Luba; Uribarri, Jaime; Kent, Rebecca; Mantha-Thaler, Kamala; Polmanteer, Lynn; Fendt, Megan; Kalaj, Anita; McKee, Elizabeth; Tripp, Elizabeth; Pyzik, Renata A.; Tirri, Lauren; Kruckelmann, Johanna F.; Swamy, Shobha M.; Chen, Xue; Cai, Weijing; Elliot, Sharon J.

In: Clinical Journal of the American Society of Nephrology, Vol. 10, No. 5, 01.01.2015, p. 759-766.

Research output: Contribution to journalArticle

Yubero-Serrano, EM, Woodward, M, Poretsky, L, Vlassara, H, Striker, GE, Age-Less Study Group, SG, Poretsky, L, Vlassara, H, Striker, GE, Busta, A, Harbord, NB, Dadzie, K, Islam, J, Ali, U, Tamler, R, Parikh, G, Rayfield, E, Rakhlin, L, Uribarri, J, Kent, R, Mantha-Thaler, K, Polmanteer, L, Fendt, M, Kalaj, A, McKee, E, Tripp, E, Pyzik, RA, Tirri, L, Kruckelmann, JF, Swamy, SM, Chen, X, Cai, W & Elliot, SJ 2015, 'Effects of sevelamer carbonate on advanced glycation end products and antioxidant/pro-oxidant status in patients with diabetic kidney disease', Clinical Journal of the American Society of Nephrology, vol. 10, no. 5, pp. 759-766. https://doi.org/10.2215/CJN.07750814
Yubero-Serrano, Elena M. ; Woodward, Mark ; Poretsky, Leonid ; Vlassara, Helen ; Striker, Gary E. ; Age-Less Study Group, Study Group ; Poretsky, Leonid ; Vlassara, Helen ; Striker, Gary E. ; Busta, Agustin ; Harbord, Nikolas B. ; Dadzie, Kobena ; Islam, Julie ; Ali, Usman ; Tamler, Ronald ; Parikh, Grishma ; Rayfield, Eliot ; Rakhlin, Luba ; Uribarri, Jaime ; Kent, Rebecca ; Mantha-Thaler, Kamala ; Polmanteer, Lynn ; Fendt, Megan ; Kalaj, Anita ; McKee, Elizabeth ; Tripp, Elizabeth ; Pyzik, Renata A. ; Tirri, Lauren ; Kruckelmann, Johanna F. ; Swamy, Shobha M. ; Chen, Xue ; Cai, Weijing ; Elliot, Sharon J. / Effects of sevelamer carbonate on advanced glycation end products and antioxidant/pro-oxidant status in patients with diabetic kidney disease. In: Clinical Journal of the American Society of Nephrology. 2015 ; Vol. 10, No. 5. pp. 759-766.
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title = "Effects of sevelamer carbonate on advanced glycation end products and antioxidant/pro-oxidant status in patients with diabetic kidney disease",
abstract = "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, & measurements This two-center, randomized, intention-to-treat, open-label study evaluated 117 patients with T2DM(HbA1c.6.5{\%}) and stages 2–4 DKD (urinary albumin/creatinine ratio $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], 20.72 to 20.29; P,0.001), serum CML (95{\%} CI, 25.08 to 21.35; P≤0.001), and intracellular CML (95{\%} CI, 21.63 to 20.28; 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 a (95{\%} CI, 1.38 to 2.73; P ≤0.001). SC also decreased proinflammatory factors such as TNF receptor 1 (95{\%} CI, 21.56 to 20.72; P≤0.001) and the receptor for AGEs (95{\%} CI, 20.58 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, 21.71 to 20.27; P=0.01, interaction P=0.002), and reduced albuminuria in those aged,65 years (95{\%} CI, 21.15 to 20.07; P=0.03, interaction P=0.02) and non-Caucasians (95{\%} CI, 21.11 to 20.22; 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.",
author = "Yubero-Serrano, {Elena M.} and Mark Woodward and Leonid Poretsky and Helen Vlassara and Striker, {Gary E.} and {Age-Less Study Group}, {Study Group} and Leonid Poretsky and Helen Vlassara and Striker, {Gary E.} and Agustin Busta and Harbord, {Nikolas B.} and Kobena Dadzie and Julie Islam and Usman Ali and Ronald Tamler and Grishma Parikh and Eliot Rayfield and Luba Rakhlin and Jaime Uribarri and Rebecca Kent and Kamala Mantha-Thaler and Lynn Polmanteer and Megan Fendt and Anita Kalaj and Elizabeth McKee and Elizabeth Tripp and Pyzik, {Renata A.} and Lauren Tirri and Kruckelmann, {Johanna F.} and Swamy, {Shobha M.} and Xue Chen and Weijing Cai and Elliot, {Sharon J.}",
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TY - JOUR

T1 - Effects of sevelamer carbonate on advanced glycation end products and antioxidant/pro-oxidant status in patients with diabetic kidney disease

AU - Yubero-Serrano, Elena M.

AU - Woodward, Mark

AU - Poretsky, Leonid

AU - Vlassara, Helen

AU - Striker, Gary E.

AU - Age-Less Study Group, Study Group

AU - Poretsky, Leonid

AU - Vlassara, Helen

AU - Striker, Gary E.

AU - Busta, Agustin

AU - Harbord, Nikolas B.

AU - Dadzie, Kobena

AU - Islam, Julie

AU - Ali, Usman

AU - Tamler, Ronald

AU - Parikh, Grishma

AU - Rayfield, Eliot

AU - Rakhlin, Luba

AU - Uribarri, Jaime

AU - Kent, Rebecca

AU - Mantha-Thaler, Kamala

AU - Polmanteer, Lynn

AU - Fendt, Megan

AU - Kalaj, Anita

AU - McKee, Elizabeth

AU - Tripp, Elizabeth

AU - Pyzik, Renata A.

AU - Tirri, Lauren

AU - Kruckelmann, Johanna F.

AU - Swamy, Shobha M.

AU - Chen, Xue

AU - Cai, Weijing

AU - Elliot, Sharon J.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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, & measurements This two-center, randomized, intention-to-treat, open-label study evaluated 117 patients with T2DM(HbA1c.6.5%) and stages 2–4 DKD (urinary albumin/creatinine ratio $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], 20.72 to 20.29; P,0.001), serum CML (95% CI, 25.08 to 21.35; P≤0.001), and intracellular CML (95% CI, 21.63 to 20.28; 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 a (95% CI, 1.38 to 2.73; P ≤0.001). SC also decreased proinflammatory factors such as TNF receptor 1 (95% CI, 21.56 to 20.72; P≤0.001) and the receptor for AGEs (95% CI, 20.58 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, 21.71 to 20.27; P=0.01, interaction P=0.002), and reduced albuminuria in those aged,65 years (95% CI, 21.15 to 20.07; P=0.03, interaction P=0.02) and non-Caucasians (95% CI, 21.11 to 20.22; 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.

AB - 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, & measurements This two-center, randomized, intention-to-treat, open-label study evaluated 117 patients with T2DM(HbA1c.6.5%) and stages 2–4 DKD (urinary albumin/creatinine ratio $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], 20.72 to 20.29; P,0.001), serum CML (95% CI, 25.08 to 21.35; P≤0.001), and intracellular CML (95% CI, 21.63 to 20.28; 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 a (95% CI, 1.38 to 2.73; P ≤0.001). SC also decreased proinflammatory factors such as TNF receptor 1 (95% CI, 21.56 to 20.72; P≤0.001) and the receptor for AGEs (95% CI, 20.58 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, 21.71 to 20.27; P=0.01, interaction P=0.002), and reduced albuminuria in those aged,65 years (95% CI, 21.15 to 20.07; P=0.03, interaction P=0.02) and non-Caucasians (95% CI, 21.11 to 20.22; 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.

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