Abstract
Background
The non-calcium-based phosphate binder sevelamer hydrochloride was developed to provide chronic kidney disease patients with a polymer capable of managing hyperphosphatemia without an increase in the calcium load. These beneficial effects were postulated as the mechanism of decreased progression of vascular calcification observed with such compounds. Our objective was to investigate the effect of low-dose sevelamer hydrochloride against calcium carbonate as phosphate binders on the coronary artery calcification score ( CCS) and the fibroblast growth factor 23 ( FGF23) level in patients receiving regular hemodialysis for more than 1 year, in a trial to find out a novel mechanism for the decreased vascular calcification observed during sevelamer use.
Patients and methods
A total of 80 hemodialysis patients were allocated into two groups each of 40 patients. The first group received sevelamer hydrochloride 2400 mg/day (group 1), whereas the second continued on calcium carbonate 1500 mg/day (group 2). For each patient, coronary artery calcification was estimated twice, once before admission to the study and again at the end of the study period using noncontrast computed tomography. Serum calcium, phosphorus, intact parathyroid hormone ( PTH), lipids, and FGF23 were also assessed in these two situations.
Results
Beside the significant decrease in serum calcium and phosphorus levels after the use of sevelamer for 6 months, there was a significant decrease in levels of FGF23 and the rate of CCS progress in group 1. Serum levels of total and low-density lipoprotein cholesterol decreased significantly in group 1. The serum PTH level did not show a significant change in either group. CCS showed a significant positive correlation with FGF23, but there was no significant correlation with serum calcium, serum phosphorus, or serum PTH in both groups.
Conclusion
Sevelamer hydrochloride suppressed the progression of coronary artery calcification, and decreased the FGF23 level significantly. The significant correlation between the serum FGF23 level and the CCS in the absence of any significant correlation between the latter on the one hand and the serum calcium, the serum phosphorus, or the serum PTH on the other might highlight a novel mechanism of action of sevelamer on the CCS.
Article PDF
Similar content being viewed by others
References
Mizobuchi M, Towler D, Slatopolsky E. Vascular calcification: the killer of patients with chronic kidney disease. J Am Soc Nephrol 2009; 20: 1453–1464.
Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000; 342: 1478–1483.
Efstratiadis G, Koskinas K, Pagourelias E. Coronary calcification in patients with end-stage renal disease: a novel endocrine disorder? Hormones (Athens) 2007; 6: 120–131.
Chertow GM, Burke SK, Raggi P Treat to Goal Working Group. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002; 62: 245–252.
Ketteler M, Shlieper G, Floege J. Calcification and cardiovascular health: new insights into an old phenomenon. Hypertension 2006; 47: 1027–1034.
Mason MA, Shepler BM. Evaluation of morbidity and mortality data related to cardiovascular calcification from calcium-containing phosphate binder use in patients undergoing hemodialysis. Pharmacotherapy2010; 30: 741–748.
Viaene L, Bammens B, Meijers BK, Vanrenterghem Y, Vanderschueren D, Evenepoel P. Residual renal function is an independent determinant of serum FGF-23 levels in dialysis patients. Nephrol Dial Transplant 2012; 27: 2017–2022.
Imanishi Y, Inaba M, Nakatsuka K, Nagasue K, Okuno S, Yoshihara A, et al. FGF-23 in patients with end-stage renal disease on hemodialysis. Kidney Int 2004; 65: 1943–1946.
Nasrallah MM, El-Shehaby AR, Salem MM, Osman NA, El Sheikh E, Sharaf El Din UA. Fibroblast growth factor-23 (FGF-23) is independently correlated to aortic calcification in haemodialysis patients. Nephrol Dial Transplant 2010; 25: 2679–2685.
Gutiérrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008; 359: 584–592.
Russo D, Battaglia Y. Clinical significance of FGF-23 in patients with ckd. Int J Nephrol 2011; 2011: 364890.
Isakova T, Gutiérrez OM, Chang Y, Shah A, Tamez H, Smith K, et al. Phosphorus binders and survival on hemodialysis. J Am Soc Nephrol 2009; 20: 388–396.
Block GA, Raggi P, Bellasi A, Kooienga L, Spiegel DM. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int 2007; 71: 438–441.
Qunibi W, Moustafa M, Muenz LR, He DY, Kessler PD, Diaz-Buxo JA, Budoff MCARE-2 Investigator. A 1-year randomized trial of calcium acetate versus sevelamer on progression of coronary artery calcification in hemodialysis patients with comparable lipid control: the Calcium Acetate Renagel Evaluation (CARE-2) study. Am J Kidney Dis 2008; 51: 952–965.
Jamal SA, Sharon M. Moe calcium builds strong bones, and more is better – correct? Well, maybe not. Clin J Am Soc Nephrol 2012; 7: 1877–1883.
Barreto DV, Barreto Fde C, Carvalho AB, Cuppari L, Draibe SA, Dalboni MA, et al. Association of changes in bone remodeling and coronary calcification in hemodialysis patients: a prospective study. Am J Kidney Dis 2008; 52: 1139–1150.
Levin A. Clinical epidemiology of cardiovascular disease in chronic kidney d isease prior to dialysis. Semin Dial 2003; 16: 101–105.
Gutiérrez OM, Januzzi JL, Isakova T, Laliberte K, Smith K, Collerone G, et al. Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 2009; 119: 2545–2552.
Cozzolino M, Missaglia E, Ortiz A. Vascular calcification in chronic kidney disease. Recenti Prog Med 2010; 101: 442–452.
Koiwa F, Kazama JJ, Tokumoto A, Onoda N, Kato H, Okada T, et al. ROD21 Clinical Research Group. Sevelamer hydrochloride and calcium bicarbonate reduce serum fibroblast growth factor 23 levels in dialysis patients. Ther Apher Dial 2005; 9: 336–339.
Isakova T, Gutierrez OM, Smith K. Pilot study of dietary phosphorus restriction and phosphorus binders to target fibroblast growth factor 23 in patients with chronic kidney disease. Nephrol Dial Transplant 2011; 26: 584–591.
Mirza MA, Larsson A, Lind L, Larsson TE. Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 2009; 205: 385–390.
Behets GJ, Dams G, Damment SJ, Martin P, De Broe ME, D’Haese PC. Differences in gastrointestinal calcium absorption after the ingestion of calcium-free phosphate binders. Am J Physiol Renal Physiol 2014; 306: F61–F67.
Lin HH, Liou HH, Wu MS, Lin CY, Huang CC. Long-term sevelamer treatment lowers serum fibroblast growth factor 23 accompanied with increasing serum Klotho levels in chronic haemodialysis patients. Nephrology (Carlton) 2014; 19: 672–678.
Author information
Authors and Affiliations
Corresponding author
Additional information
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
Rights and permissions
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Zayed, B.E., El-Fishawy, H., Al-Shihaby, A.R. et al. Sevelamer hydrochloride and coronary artery calcification in chronic hemodialysis patients: a new mechanism of action. Egypt J Intern Med 27, 133–138 (2015). https://doi.org/10.4103/1110-7782.174928
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.4103/1110-7782.174928