Literature DB >> 21299254

Pleiotropic effects of sevelamer beyond phosphate binding in end-stage renal disease patients: a randomized, open-label, parallel-group study.

Yu-Feng Lin1, Chiang-Ting Chien, Wei-Chih Kan, Yung-Ming Chen, Tzong-Shinn Chu, Kuan-Yu Hung, Tun-Jun Tsai, Kwan-Dun Wu, Ming-Shiou Wu.   

Abstract

BACKGROUND AND
OBJECTIVE: Hyperphosphataemia in end-stage renal disease (ESRD) is a major contributor to the development of cardiovascular disease. It has been proposed that the phosphate binder sevelamer has pleiotropic properties. The aim of this study was to evaluate the effects of sevelamer compared with calcium acetate on serum lipid profiles, uric acid and reactive oxygen species in haemodialysis patients with hyperphosphataemia.
METHODS: An 8-week, randomized, open-label, parallel-group study was conducted after a 2-week washout period. A total of 52 patients with ESRD on maintenance haemodialysis were screened for enrolment; 26 patients were randomized to each of the sevelamer and calcium acetate groups. Reactive oxygen species (ROS) production, i.e. superoxide and hydrogen peroxide (H2O2)-related radicals, were detected by chemiluminescence measurement with lucigenin and luminol, respectively.
RESULTS: There were no significant differences between treatment groups in changes in serum phosphorus (p=0.378) and adjusted serum calcium levels (p=0.980), but there were more hypercalcaemic events in the calcium acetate group (12.0% vs 3.7%) during treatment. Total serum cholesterol (p<0.001) and low-density lipoprotein (LDL) cholesterol (p<0.001) levels decreased significantly compared with baseline in the sevelamer group. The decreases in total serum cholesterol and LDL cholesterol were correlated with the reductions in serum phosphorus levels during sevelamer treatment (correlation coefficient [r]=0.266 and 0.386, respectively). Serum uric acid decreased significantly in the sevelamer group (p=0.020), and this change was correlated with serum phosphorus changes (r=0.458). Decreases in plasma H2O2-related radicals, the major oxidative stressor in ROS (p<0.001), but not superoxide (p=0.593), were observed after sevelamer treatment.
CONCLUSION: The improvements in multiple lipid surrogates, uric acid and ROS seen in this study show that sevelamer is a promising therapy for treatment of hyperphosphataemia in maintenance haemodialysis patients with a high risk of cardiovascular disease.

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Year:  2011        PMID: 21299254     DOI: 10.2165/11539120-000000000-00000

Source DB:  PubMed          Journal:  Clin Drug Investig        ISSN: 1173-2563            Impact factor:   2.859


  42 in total

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2.  Poor long-term survival after acute myocardial infarction among patients on long-term dialysis.

Authors:  C A Herzog; J Z Ma; A J Collins
Journal:  N Engl J Med       Date:  1998-09-17       Impact factor: 91.245

Review 3.  Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: recommendations for a change in management.

Authors:  G A Block; F K Port
Journal:  Am J Kidney Dis       Date:  2000-06       Impact factor: 8.860

4.  Sevelamer prevents uremia-enhanced atherosclerosis progression in apolipoprotein E-deficient mice.

Authors:  Olivier Phan; Ognen Ivanovski; Thao Nguyen-Khoa; Nadya Mothu; Jesus Angulo; Ralf Westenfeld; Markus Ketteler; Natalie Meert; Julien Maizel; Igor G Nikolov; Raymond Vanholder; Bernard Lacour; Tilman B Drüeke; Ziad A Massy
Journal:  Circulation       Date:  2005-11-01       Impact factor: 29.690

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10.  Effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary heart disease: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study.

Authors:  Vasilios G Athyros; Moses Elisaf; Athanasios A Papageorgiou; Athanasios N Symeonidis; Anthimos N Pehlivanidis; Vasilios I Bouloukos; Haralambos J Milionis; Dimitri P Mikhailidis
Journal:  Am J Kidney Dis       Date:  2004-04       Impact factor: 8.860

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  11 in total

1.  Survival Benefit of Statins in Hemodialysis Patients Awaiting Renal Transplantation.

Authors:  Waqas Aftab; Juliana Gazallo; Ali Motabar; Padmini Varadrajan; Prakash C Deedwania; Ramdas G Pai
Journal:  Int J Angiol       Date:  2015-06

2.  Comparative effectiveness of calcium acetate and sevelamer on clinical outcomes in elderly hemodialysis patients enrolled in Medicare part D.

Authors:  Akeem A Yusuf; Eric D Weinhandl; Wendy L St Peter
Journal:  Am J Kidney Dis       Date:  2013-12-31       Impact factor: 8.860

3.  Clinical factors associated with serum copper levels and potential effect of sevelamer in hemodialysis patients.

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Journal:  Int Urol Nephrol       Date:  2012-06-09       Impact factor: 2.370

Review 4.  Sevelamer carbonate: a review in hyperphosphataemia in adults with chronic kidney disease.

Authors:  Caroline M Perry; Greg L Plosker
Journal:  Drugs       Date:  2014-05       Impact factor: 9.546

Review 5.  Phosphate binders in chronic kidney disease: a systematic review of recent data.

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Review 6.  Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD: A Meta-Analysis of Randomized Controlled Trials.

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7.  Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD).

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8.  Effectiveness of fibroblast growth factor 23 lowering modalities in chronic kidney disease: a systematic review and meta-analysis.

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Review 9.  Sevelamer revisited: pleiotropic effects on endothelial and cardiovascular risk factors in chronic kidney disease and end-stage renal disease.

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Journal:  Ther Adv Cardiovasc Dis       Date:  2013-12

Review 10.  The Strategy to Prevent and Regress the Vascular Calcification in Dialysis Patients.

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