Effect of Phosphate Binders on Vascular Calcification and Mortality in Korean Patients with Chronic Kidney Disease

만성신부전 환자의 혈관 석회화와 사망률에 미치는 인결합제의 영향

  • Sin, Hye Yeon (College of Pharmacy, Duksung Women's University)
  • 신혜연 (덕성여자대학교 약학대학)
  • Received : 2014.04.06
  • Accepted : 2014.07.03
  • Published : 2014.09.30

Abstract

Objectives: Current studies are debating on the association of vascular calcification and the benefit of treatment to lower serum phosphorus level in patients with chronic kidney disease. The aim of this study was to evaluate the association of mortality and risk of vascular calcification in patients with CKD who were taking phosphate binders. Methods: This study was conducted through retrospective medical chart review for 420 patients aged 18 years and older who were admitted for chronic kidney disease. Results: Vascular calcification was not statistically significantly associated with increased mortality in patients with CKD [16.7% vs. 19.2%; 95% CI; 0.388 to 1.818 (p=0.656)]. Intervention of calcium-based phosphate binders was not significantly associated with vascular calcification in patients with CKD [9.1% vs. 12.5%; 95% CI; 0.364 to 1.358 (p=0.292)]. Ca x P product ${\geq}55mg^2/dL^2$ was not significantly associated with increased 1 year mortality in patients with CKD [25.4% vs. 17.5%; 95% CI; 0.851 to 3.013 (p=0.142)]. Intervention of sevelamer was significantly associated with reduced 1 year mortality in patients with CKD than that of patients who did not take sevelamer [6.3% vs. 25.3%; 95% CI; 0.044 to 0.880 (p=0.020)]. Conclusion: There was not a statistically significant association between vascular calcification and phosphate binder's use. But phosphate binder use was significantly associated with decreased mortality in patients with CKD.

Keywords

References

  1. Moorthi RN, Moe SM. CKD-Mineral and bone disorder: Core Curriculum 2011. Am J Kidney Dis 2011;58:1022-36. https://doi.org/10.1053/j.ajkd.2011.08.009
  2. Rodriguez-Ortiz ME, Lopez I, Munoz-Castaneda JR, et al. Calcium deficiency reduces circulating levels of FGH23. J Am Soc Nephrol 2012;23:1190-97. https://doi.org/10.1681/ASN.2011101006
  3. Bellinghieri G, Santoro D, Savica V. Emerging drugs for hyperphosphatemia. Expert Opin. Emerging Drugs 2007;12: 355-65.
  4. Uhlig K, Berns JS, Kestenbaum B, et al. KDOQI US Commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD- Mineral and Bone Disorder (CKD-MBD). Am J Kid Dis 2010;55:773-99. https://doi.org/10.1053/j.ajkd.2010.02.340
  5. Seaghdhaa CM, Hwang SJ, Muntner P, et al. Serum phosphorus predicts incident chronic kidney disease and end-stage renal disease. Nephrol Dial Transplant 2011;26:2885-90. https://doi.org/10.1093/ndt/gfq808
  6. Barreto DV, Barreto Fde C, de Carvalho AB, et al. Phosphate binder impact on bone remodeling and coronary calcification--results from the BRiC study. Nephron Clin Pract 2008;110:c273-83. https://doi.org/10.1159/000170783
  7. Block G A, Raggi P, Bellasi A, et al. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int 2007;71:438-41. https://doi.org/10.1038/sj.ki.5002059
  8. Qunibi W, Moustafa M, Muenz LR, et al. CARE-2 Investigators. 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-2 (CARE-2) study. Am J Kidney Dis 2008;51:952-65. https://doi.org/10.1053/j.ajkd.2008.02.298
  9. Coen G, Manni M, Mantella D, et al. Are PTH serum levels predictive of coronary calcifications in haemodialysis patients. Nephrol Dial Transplant 2007;22:3262-67. https://doi.org/10.1093/ndt/gfm370
  10. Barreto FC, Barreto DV, Liabeuf S, et al. Effects of uremic toxins on vascular and bone remodeling. Semin Dial 2009;22:433-37. https://doi.org/10.1111/j.1525-139X.2009.00595.x
  11. Moe SM, Chen NX. Mechanism of vascular calcification in CKD. J Am Soc Nephrol 2008;19:213-16. https://doi.org/10.1681/ASN.2007080854
  12. McCullough PA, Chinnaiyan KM. Annual progression of coronary calcification in trials of preventive therapies. Arch Intern Med 2009;169:2064-70. https://doi.org/10.1001/archinternmed.2009.382
  13. Lau WL, Pai A, Moe SM, et al. Direct effects of phosphate on vascular cell function. Adv Chronic Kidney Dis 2011;18:105-12. https://doi.org/10.1053/j.ackd.2010.12.002
  14. Levey AS, Josef CJ, Bolton K, et al. National kidney foundation KDOQI clinical practice guideline for chronic kidney disease; evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1-S266.
  15. Budoff MJ, Rader DJ, Reilly MP. Relationship of estimated GFR and coronary artery calcification in the CRIC (Chronic Renal Insufficiency Cohort) study. Am J Kidney Dis 2011;58:519-26. https://doi.org/10.1053/j.ajkd.2011.04.024
  16. Chen NX, Moe SM. Vascular calcification: Pathophysiology and risk factors. Curr Hypertens Rep 2012;14:228- 37. https://doi.org/10.1007/s11906-012-0265-8
  17. Suki WN, Zabaneh R, Cangiano JL, et al. Effect of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. Kidney International 2007;72:1130-37. https://doi.org/10.1038/sj.ki.5002466
  18. Navaneethan SD, Palmer SC, Craig JC, et al. Benefits and Harms of Phosphate Binders in CKD: A Systematic Review of Randomized Controlled Trials. Am J Kid Dis 2009;54:619-37. https://doi.org/10.1053/j.ajkd.2009.06.004
  19. Moe SM, Drueke TB, Block GA, et al. KDIGO clinical guideline for the management of CKD-MBD. Kidney Int 2009;76:S1-S130.
  20. Suetonia C, Palmer AH, Peter M, et al. Serum levels of phosphorous, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease (a systemic review and metaanalysis). JAMA 2011;305:1119-27. https://doi.org/10.1001/jama.2011.308
  21. Stevens LA, Li S, Wang C, et al. Prevalence of CKD and Comorbid Illness in Elderly Patients in the United States: Results From the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis 2010;55:S1-S28. https://doi.org/10.1053/S0272-6386(10)00603-7
  22. Snyder JJ, Collins AJ. Association of preventive health care with atherosclerotic heart disease and mortality in CKD. J Am Soc Nephrol 2009;20:1614-22. https://doi.org/10.1681/ASN.2008090954
  23. United States Renal Data System (USRDS) annual data report. 1 2013;74:81-82.
  24. Reynolds JL, Joannides AJ, Skepper JN, et al. Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to change in extracellular calcium and phosphate concentration: A potential mechanism for accelerated vascular calcification in ESRD. J Am Soc Nephrol 2004;15:2857-67. https://doi.org/10.1097/01.ASN.0000141960.01035.28
  25. Cecilia MG. The emerging role of phosphate in vascular calcification. Kidney Int 2009;75:890-97. https://doi.org/10.1038/ki.2008.644
  26. O'Neill WC. The fallacy of the calcium-phosphorus product. Kid Intern 2007;72:776-92.
  27. Terai K, Nara H, Takakura K, et al. Vascular calcification and secondary hyperparathyroidism of severe chronic kidney disease and its relation to serum phosphate and calcium levels. British J Pharm 2009;156:1267-1278. https://doi.org/10.1111/j.1476-5381.2008.00108.x
  28. Linefsky JP, O'Brien KD, DPhil RK, et al. Vascular calcification and secondary hyperparathyroidism of severe chronic kidney disease and its relation to serum phosphate and calcium levels. J Am Coll Cardiol 2011;58:291-297. https://doi.org/10.1016/j.jacc.2010.11.073
  29. Wolf M, Shah A, Gutierrez O, et al. Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Intern 2007;72:1004-1013. https://doi.org/10.1038/sj.ki.5002451
  30. Foley RN, Collins AJ, Kalra PA. Calcium-phosphate levels and cardiovascular disease in community-dwelling adults. The atherosclerosis risk in communities (ARIC) study. Am Heart J 2008;156:556-63. https://doi.org/10.1016/j.ahj.2008.05.016
  31. Foley RN, Collins AJ, Chales A, et al. Serum phosphate and left ventricular hypertrophy in young adults: The coronary artery risk development in young adults study. Kidney Blood Press Res 2009;32:37-44. https://doi.org/10.1159/000203348
  32. Hutchison A J. Oral phosphate binders. Kid Intern 2009;75:906-914. https://doi.org/10.1038/ki.2009.60