Korean Journal of Clinical Pharmacy (한국임상약학회지)

Korean College Of Clinical Pharmacy (한국임상약학회)
권호 표지

Management of Chronic Kidney Disease-Mineral Bone Disorder with Sevelamer Hcl Phosphate Binder in Korean Patients with Dialysis

Sevelamer 인결합제와 투석환자의 Chronic Kidney Disease-Mineral Bone Disorder 관리

  • 신승우 (강릉아산병원 약제팀) ;
  • 신혜연 (덕성여자대학교 약학대학)
  • Received : 2016.02.04
  • Accepted : 2016.06.04
  • Published : 2016.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Sevelamer is associated with reduced complications of chronic kidney disease-mineral bone disorder (CKD-MBD) resulted from hyperphosphatemia, which may contribute mortality, in CKD patients with dialysis. So far clinical outcomes of sevelamer on mortality and risk of cardiovascular mortality related to CKD-MBD are debating. Purpose of this study was to evaluate the effectiveness of sevelamer HCl on mortality of secondary hyperparathyroidism (SHPT), risk of cardiovascular mortality and, frequency of osteopathy in end stage renal disease (ESRD) patients with dialysis. Methods: We retrospectively reviewed the electronic medical records of 536 patients with ESRD, who were admitted for moderate to severe SHPT, for 36 months. 75 patients who met inclusion criteria were evaluated for the efficacy of sevelamer (mean serum iPTH = 487.5 pg/mL). Results: Sevelamer intervention was not associated with increased three-year survival time compared with non-sevelamers group [average survival month: 30.4 months in sevelamer group, 26.8 months in non-sevelamer group, p = 0.463]. Sevelamer intervention was not associated with significant mortality benefit and cardiovascular mortality benefit as compared to non-sevelamer group [sevelamer group: non-sevelamer group, all-cause mortality (iPTH > 600 pg/mL): 14.3% (1/34): 20% (1/41) p = 0.962, OR = 0.935, 95% CI, 0.058-14.98, heart disease mortality: 6.67% (2/30): 0% (0/32) p = 0.138]. Sevelamer was not associated with significantly lower cumulative incidence of osteopathy compared to non-sevelamer group (sevelamer group: non-sevelamer group, 5.9% (2/34):9.8% (4/41); p = 0.538; OR = 0.578; 95% CI, 0.099-3.367). Conclusion: Sevelamer was not associated with decreased all-cause mortality and risk of cardiovascular mortality compared to non-sevelamer group in ESRD patients with SHPT.

Keywords

References

  1. Block GA. How should hyperphosphatemia be managed in dialysis patients. Semin Dial 2002;15:315-17. https://doi.org/10.1046/j.1525-139X.2002.00077_1.x
  2. Block GA, Klassen PS, Lazarus JM, et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004;15:2208-18. https://doi.org/10.1097/01.ASN.0000133041.27682.A2
  3. Kestenbaum B. Phosphate metabolism in the setting of chronic kidney disease: Significance and recommendations for treatment. Semin Dial 2007;20(4):286-94. https://doi.org/10.1111/j.1525-139X.2007.00303.x
  4. Amann K, Tornig J, Kugel B, et al. Hyperphosphatemia aggravates cardiac fibrosis and microvascular disease in experimental uremia. Kidney Int 2003;63:1296-301. https://doi.org/10.1046/j.1523-1755.2003.00864.x
  5. Mathew S, Tustison KS, Sugatani T, et al. The mechanism of phosphorus as a cardiovascular risk factor in CKD. J Am Soc Nephrol 2008;19:1092-105. https://doi.org/10.1681/ASN.2007070760
  6. Toussaint ND, Pedagogos E, Jeantan S, et al. Phosphate in early chronic kidney disease: Associations with clinical outcomes and a target to reduce cardiovascular risk. Nephrolo 2012;17:433-44. https://doi.org/10.1111/j.1440-1797.2012.01618.x
  7. Fukagawa M, Yokoyama K, Koiwa F, et al. CKD-MBD guideline working group, clinical practice gfor the management of chronic kidney disease-mineral and bone disorder. Ther Apher Dial 2013;17(3):247-88. https://doi.org/10.1111/1744-9987.12058
  8. Elder G. Pathophysiology and recent advances in the management of renal osteodystrophy. J Bone Miner Res 2002;17:2094-105. https://doi.org/10.1359/jbmr.2002.17.12.2094
  9. Fukagawa M, Yokoyama K, Koiwa F, et al. CKD-MBD guideline working group; Japanese society 2 for dialysis therapy. Clinical practice guideline for the management of chronic kidney disease mineral and bone disorder. Ther Apher Dial 2013;17(3):247-288. https://doi.org/10.1111/1744-9987.12058
  10. Levin A, Bakris GL, Molitch M, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: Results of the study to evaluate early kidney disease. Kidney Int 2007;71:31-8. https://doi.org/10.1038/sj.ki.5002009
  11. Wills MR, Savory J. Aluminum poisoning: dialysis encephalopathy, osteomalacia and anemia. Lancet 1983;2:29-34.
  12. Block GA, Persky MS, Ketteler M, et al. A randomized double-blind pilot study of serum phosphorus normalization in chronic kidney disease: A new paradigm for clinical outcomes studies in nephrology. Hemodial Int 2009;13:360-62. https://doi.org/10.1111/j.1542-4758.2009.00387.x
  13. Tonelli M, Pannu N, Manns B, et al. Oral phosphate binders in patients with Kidney failure. New EngL J Med 2010;362:1312-24. https://doi.org/10.1056/NEJMra0912522
  14. Suki WN, Zabaneh R, Cangiano JL, et al. Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. Kidney Int 2007;72:1130-37. https://doi.org/10.1038/sj.ki.5002466
  15. Block GA, 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
  16. Panichi V, Bigazzi R, Paoletti S, et al. Impact of calcium, phosphate, PTH abnormalities and management on mortality in hemodialysis: results from the RISCAVID study. J Nephrol 2010;23:556-62.
  17. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42 (Suppl 3):S1-201.
  18. National collaborating centre for chronic conditions. Chronic Kidney Disease: National clinical guideline for early identification and management in adults in primary and secondary care. London: Royal College of physicians (UK), 2008. (NICE Clinical Guidelines, No.73).
  19. The kidney disease: Improving global outcomes (KDIGO) work group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int 2009;113:S1-130.
  20. Stuatevant JM, Hawley CM, Reiger K, et al. Efficacy and side-effect profile of sevelamer hydrochloride used in combination with conventional phosphate binders. Nephrol 2004;9:406-13. https://doi.org/10.1111/j.1440-1797.2004.00338.x
  21. Marangon N, Lindholm B, Stenvinkel P, et al. Nonphosphate-binding effects of sevelamer-Are they of clinical relevance? Semin Dial 2008;21:385-89. https://doi.org/10.1111/j.1525-139X.2008.00440.x
  22. Adeney KL, Siscovick DS, Ix JH, et al. Association of serum phosphate with vascular and valvular calcification in moderate CKD. J Am Soc Nephrol 2009;20:381-87. https://doi.org/10.1681/ASN.2008040349
  23. Dhingra R, Sullivan L, Fox S, et al. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch. Int. Med 2007;167:879-85. https://doi.org/10.1001/archinte.167.9.879
  24. Braun J, Odendorf M, Moshage W, et al. Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kidney Dis 1996;27:394-401. https://doi.org/10.1016/S0272-6386(96)90363-7
  25. Patel L, Bernard LM, Elder GJ, et al. Sevelamer versus calcium-based binders for treatment of hyperphosphatemia in CKD: A meta-analysis of randomized controlled trials. Clin J Am Soc Nephrol. 2016;11:232-44. https://doi.org/10.2215/CJN.06800615
  26. Wang C, Liu X, Zhou Y, et al. New Conclusions Regarding Comparison of Sevelamer and Calcium-Based Phosphate Binders in Coronary-Artery Calcification for Dialysis Patients: A meta-analysis of randomized controlled trials. PLoS One 2015;10(7):e0133938. https://doi.org/10.1371/journal.pone.0133938
  27. Danese MD, Kim J, Doan QV, et al. PTH and the risks for hip, vertebral, and pelvic fractures among patients on dialysis. Am J Kidney Dis 2006;47:149-56. https://doi.org/10.1053/j.ajkd.2005.09.024
  28. Floege J, Kim J, Ireland E, et al. Serum iPTH, calcium and phosphate, and the risk of mortality in a European haemodialysis population. Nephrol Dial Transplant. 2011;26:1948-55. https://doi.org/10.1093/ndt/gfq219
  29. Jean G, Lataillade D, Genet L, et al. Calcium carbonate, but not sevelamer, is associated with better outcomes in hemodialysis patients: Results from the French ARNOS study. Hemodial Int. 2011;15:485-92. https://doi.org/10.1111/j.1542-4758.2011.00575.x
  30. Liu L, Wang Y, Chen H, et al. The effects of non-calcium-based phosphate binders versus calcium-based phosphate binders on cardiovascular calcification and bone remodeling among dialysis patients: a metaanalysis of randomized trials. Ren Fail 2014;36:1244-52. https://doi.org/10.3109/0886022X.2014.938544
  31. Locatelli F, Del Vecchio L. Cardiovascular mortality in chronic kidney disease patients: potential mechanisms and possibilities of inhibition by resin-based phosphate binders. Expert Rev Cardiovasc Ther 2015;13:489-99. https://doi.org/10.1586/14779072.2015.1029456
  32. Chertow GM, Raggi P, Chasan-Taber S, et al. Determinants of progressive vascular calcification in haemodialysis patients. Nephrol Dial Transplant 2004;19:1489-96. https://doi.org/10.1093/ndt/gfh125
  33. Chiu Y-W, Adler SG, Budoff MJ, et al. Coronary artery calcification and mortality in diabetic patients with proteinuria. Kidney Int 2010;77:1107-14. https://doi.org/10.1038/ki.2010.70
  34. Isakova T, Gutiérrez OM, Chang Y, et al. Phosphorus binders and survival on hemodialysis. J. Am. Soc. Nephrol 2009;20:388-96. https://doi.org/10.1681/ASN.2008060609
  35. Lin Y-F, Chen Y-M, Kuan-Yu, et al. Benefits of sevelamer on markers of bone turnover in Taiwanese hemodialysis patients. J Formos Med Assoc 2010;109:663-72. https://doi.org/10.1016/S0929-6646(10)60107-6
  36. 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 Kidney Dis 2009;54:619-37. https://doi.org/10.1053/j.ajkd.2009.06.004
  37. Soroka SD, Beard KM, Mendelssohn DC, et al. Mineral metabolism management in Canadian peritoneal dialysis patients. Clin Nephrol 2011;75:410-5. https://doi.org/10.5414/CNP75410
  38. Ogata H, Koiwa F, Ito H, et al. Therapeutic strategies for secondary hyperparathyroidism in dialysis patients. Ther Apher Dial 2006;10:355-64. https://doi.org/10.1111/j.1744-9987.2006.00389.x
  39. Menon V, Kopple JD, Wang X, et al. Effect of a very low-protein diet on outcomes: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. Am J Kidney Dis 2009;53:208-17. https://doi.org/10.1053/j.ajkd.2008.08.009