Contemporary opportunities for using phosphate binders in dialysis patients


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Hyperphosphatemia in patients with chronic kidney disease (CKD) undergoing hemodialysis is associated with a high risk of cardiovascular morbidity and mortality. Controlling serum phosphorus has long been recognized as one of the key objectives in managing CKD patients. The main strategies in preventing and managing hyperphosphatemia are hypophosphorous diet, adequate dialysis and the use of phosphate binders. The article reviews the most commonly used phosphate binders. It discusses the pharmacokinetics, side effects, initial and maintenance doses, phosphate-binding capacity and contraindications for phosphate binders. New approaches to monitoring the serum phosphorus level in CKD patients undergoing dialysis are presented. The review describes the principles of administering phosphate binders based on their efficacy and tolerability, and considering the phosphorus load, comorbidities and contraindications. The authors present an algorithm and the results of the comparative assessment of the phosphate-binding capacity of phosphate binders based on using relative phosphate binding ratio and phosphate-binding equivalent dose to facilitate selecting the dosage of phosphate binders. High phosphate-binding capacity of phosphate binders improves the effectiveness of correcting hyperphosphatemia, decreases the medication load and improves patient's adherence to the prescribed therapy.

Full Text

Restricted Access

References

  1. Zhang Q.L., Rothenbacher D. Prevalence of chronic kidney disease in population-based studies: systematic review. BMC Public Health. 2008; 8: 117. doi: 10.1186/1471-2458-8-117.
  2. Couser W.G., Remuzzi G., Mendis S., Tonelli M. The contribution of chronic kidney disease to the global burden of major non-communicable diseases. Kidney Int. 2011; 80: 1258-1270. Doi: 10.1038/ ki.2011.368.
  3. Gonzalez-Parra E., Tunon J., Egido J., Ortiz A. Phosphate: a stealthier killer than previously thought? Cardiovas. Pathol. 2012; 21: 372-381. doi: 10.1016/j.carpath.2012.02.008.
  4. Kasiske B.L., Zeier M.G., Chapman J.R., et al.; Kidney disease: improving global outcomes. KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary. Kidney Int. 2010; 77: 299-311. doi: 10.1038/ki.2009.377.
  5. Giachelli C.M. The emerging role of phosphate in vascular calcification. Kidney Int. 2009; 75: 890-897. doi: 10.1038/ki.2008.644.
  6. Block G.A. Screening dialysis patients for vascular calcification. Semin Dial. 2010; 23(3): 271-276. doi: 10.1111/j.1525-139X.2010.00727.x.
  7. Floege J., Kim J., Ireland E., et al.; ARO Investigators. Serum iPTH, calcium and phosphate, and the risk of mortality in a European haemodialysis population. Nephrol Dial. Transplant. 2011; 26: 1948-1955. doi: 10.1093/ndt/gfq219.
  8. Tentori F., Blayney M.J., Albert J.M., et al. Mortality riskfor dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am. J. Kidney Dis. 2008; 52(3): 519-530. doi: 10.1053/j.ajkd.2008.03.020.
  9. Block G.A, Hulbert-Shearon T.E., Levin N.W., Port F.K. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am. J. Kidney Dis. 1998; 31(4): 607-617.
  10. Block G.A, Klassen P.S., Lazarus J.M., et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. JASN. 2004; 15(8): 2208-2218.
  11. Slinin Y., Foley R.N., Collins A.J. Calcium, phosphorus, parathyroid hormone, and cardiovascular disease in hemodialysis patients: the USRDS waves 1, 3, and 4 study. JASN. 2005; 16(6): 1788-1793.
  12. Lopes A.A, Tong L., Thumma J., et al. Phosphate binder use and mortality among hemodialysis patients in the dialysis outcomes and practice patterns study (dopps): evaluation of possible confounding by nutritional status. Am. J. Kidney Dis. 2012; 60(1): 90-101. doi: 10.1053/j.ajkd.2011.12.025.
  13. Kidney Disease: Improving Global Outcomes. (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney diseasemineral and bone disorder (CKD-MBD). Kidney Int. Suppl. 2009; 113: S1-S130. doi: 10.1038/ki.2009.188.
  14. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am. J. Kidney Dis. 2003; 42: S1-S201.
  15. Noori N., Kalantar-Zadeh K., Kovesdy C.P., et al. Association of dietary phosphorus intake and phosphorus to protein ratio with mortality in hemodialysis patients. Clin. J. Am. Soc. Nephrol 2010; 5(4): 683-692. doi: 10.2215/CJN.08601209.
  16. Heng A.-E., Cano N.J.M. Nutritional problems in adult patients with stage 5 chronic kidney disease on dialysis (both haemodialysis and peritoneal dialysis). NDTPlus. 2010; 3: 109-117.
  17. Shinaberger C.S., Greenland S., Kopple J.D., et al. Is controlling phosphorus by decreasing dietary protein intake beneficial or harmful in persons with chronic kidney disease? Am. J. Clin. Nutr. 2008; 88: 1511-1518. doi: 10.3945/ajcn.2008.26665.
  18. Lynch K.E., Lynch R., Curhan G.C., Brunelli S.M. Prescribed dietary phosphate restriction and survival among hemodialysis patients. Clin. J. Am. Soc. Nephrol. 2011; 6: 620-629. doi: 10.2215/CJN.04620510.
  19. Ritz E., Hahn K., Ketteler M., et al. Phosphate additives in food - a health risk. Dtsch. Arztebl. Int. 2012; 109: 49-55.
  20. Uribarri J. Phosphorus homeostasis in normal health and in chronic kidney disease patients with special emphasis on dietary phosphorus intake. Semin. Dial. 2007; 20: 295-301.
  21. Penne E.L., van der Weerd N.C., van den Dorpel M.A., et al. Short-term effects of online hemodiafiltration on phosphate control: a result from the randomized controlled Convective Transport Study (CONTRAST). Am. J. Kidney Dis. 2010; 55: 77-87.
  22. Kuhlmann M.K. Phosphate elimination in modalities of hemodialysis and peritoneal dialysis. Blood Purif. 2010; 29: 137-144. doi: 10.1159/000245640.
  23. Suri R.S., Garg A.X., Chertow G.M., et al. Frequent Hemodialysis Network (FHN) randomized trials: study design. Kidney Int. 2007; 71(4): 349-359.
  24. Movilli E., Camerini C., Gaggia P., et al. Effect of post-dilutional on-line haemodiafiltration on serum calcium, phosphate and parathyroid hormone concentrations in uraemic patients. Nephrol Dial. Transpl. 2011; 26(12): 4032-4037. doi: 10.1093/ndt/gfr179.
  25. Martin K.J., Gonzalez E.A. Prevention and control of phosphate retention/hyperphosphatemia in CKD-MBD: what is normal, when to start, and how to treat? Clin. J. Am. Soc. Nephrol. 2011; 6(2): 440-446. doi: 10.2215/CJN.05130610.
  26. Locatelli F., Altieri P., Andrulli S., et al. Phosphate levels in patients treated with low-flux haemodialysis, pre-dilution haemofiltration and haemodiafiltration: post hoc analysis of a multicentre, randomized and controlled trial. Nephrol. Dial. Transplant. 2014; 29(6): 1239-1246. doi: 10.1093/ndt/gfu031.
  27. Kalantar-Zadeh K., Kuwae N., Regidor D.L., et al. Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int. 2006; 70(4): 771-780.
  28. Covic A., Kothawala P., Bernal M., et al. Systematic review of the evidence underlying the association between mineral metabolism disturbances and risk of all-cause mortality, cardiovascular mortality and cardiovascular events in chronic kidney disease. Nephrol. Dial. Transplant. 2009; 24(5): 1506-1523. doi: 10.1093/ndt/gfn613.
  29. Isakova T., Gutiérrez O.M., Chang Y., et al. Phosphorus binder and survival on hemodialysis. J. Am. Soc. Nephrol 2009; 20: 388-396. doi: 10.1681/ASN.2008060609.
  30. Cannata-Andia J.B. The use of phosphate binding agents is associated with lower mortalityresultsfrom the COSMOS study. 49th ERA-EDTA Congress, May 24-27, 2012. Paris, France.
  31. Kakuta T., Tanaka R., Hyodo T., et al. Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients. Am. J. Kidney Dis. 2011; 57(3): 422-431. doi: 10.1053/j.ajkd.2010.10.055.
  32. Jamal S.A., Vandermeer B., Raggi P., et al. Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease:an updated systematic review and metaanalysis. Lancet. 2013; 382: 1268-1277. doi: 10.1016/S0140-6736(13)60897-1.
  33. Chertow G.M., Burke S.K, Raggi P.; Goal Working Group. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002; 62: 245-252.
  34. Block G.A, Spiegel D.M., Ehrlich J., et al. Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int. 2005; 68: 1815-1824.
  35. 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: 438-441.
  36. Spiegel D.M., Raggi P., Smits G., Block G.A. Factors associated with mortality in patients new to haemodialysis. Nephrol. Dial. Transplant. 2007; 22: 3568-3572.
  37. Renagel® [PrescribingInformation]. Cambridge: Genzyme Inc., 2014.
  38. Fosrenol® [Prescribing Information]. Wayne, PA Shire US Inc., 2014.
  39. Phoslyrd® [Prescribing Information]. Waltham, MA: Fresenius MedicaCare North America, 2011.
  40. Ренвелла®: инструкция по применению. URL: http://www.grls.rosminzdrav.ru
  41. Akizawa T., Origasa H., Kameoka C., et al.; Bixalomer Study Group. Randomized controlled trial of bixalomer versus sevelamer hydrochloride in hemodialysis patients with hyperphosphatemia. Ther. Apher. Dial. 2014;18:122-131. doi: 10.1111/1744-9987.12068.
  42. Вельфоро® 500: инструкция по применению. URL:http://www.grls.rosminzdrav.ru
  43. Auryxia® [Prescribing Information]. NY: Keryx Biopharmaceuticab, 2014.
  44. Daugirdas J.T., Finn W.F., Emmett M., Chertow G.M.; Frequent Hemo-dialysis Network Trial Group. The phosphate binder equivalent dose. Semin. Dial. 2011;24:41-49. doi: 10.1111/j.1525-139X.2011.00849.x.
  45. Daugirdas J.T., Chertow G.M., Larive B., et al.; Frequent Hemodialysis Network Trial Group. Effects of frequent hemodialysis on measures of CKD mineral and bone disorder. J. Am. Soc. Nephrol 2012;23:727-738. doi: 10.1681/ASN.2011070688.
  46. Daugirdas J.T., Blake P., Ing T. Bone disease. In: Handbook of dialysis. PA, 2015.
  47. Savica V., Bellinghieri G., Monardo P., et al. An update on calcium metabolism alterations and cardiovascular risk in patients with chronic kidney disease:questions, myths and facts. J. Nephrol. 2013; 26: 45-464. doi: 10.5301/jn.5000189.
  48. Spiegel D.M., Block G.A. Should we be using calcium-containing phosphate binder in patients on dialysis? Nat. Clin. Pract. Nephrol. 2008; 4: 118-119.
  49. Pflanz S., Henderson I.S., McElduff N., et al. Calcium acetate versus calcium carbonate as phosphate-binding agents in chronic haemodialysis. Nephrol. Dial. Transplant. 1994; 9: 1121-1124.
  50. Saif I., Halim A, Altaf A., et al. Comparison of calcium acetate with calcium carbonate as phosphate binder in patients on maintenance haemodialysis. J. Ayub. Med. Coll. Abbottabad. 2007; 19: 26-28.
  51. Choy B.Y., Lo W.K., Cheng I.K.P. Effectiveness of calcium acetate as a phosphate binder in patients undergoing continuous ambulatory peritoneal dialysis. Hong Kong Med. J. 1998; 4: 23-26.
  52. ОсваРен®: инструкция по применению. URL: http://www.grls.rosminzdrav.ru.
  53. de Francisco A.L., Leidig M., Covic A.C., et al. Evaluation of calcium acetate/magnesium carbonate as a phosphate binder compared with sevelamer hydrochloride in haemodialysis patients:a controlled randomized study (CALMAG study) assessing efficacy and tolerability. Nephrol. Dial. Transplant. 2010; 25(11): 3707-3717. doi: 10.1093/ndt/gfq292.
  54. Chertow G.M., Martin K.J. Current and future therapies for the medical management of secondary hyperparathyroidism. Semin. Dial. 1998; 11: 267-270.
  55. Slatopolsky E., Burke S.K., Dillon M.A. RenaGel, a nonabsorbed calcium- and aluminum-free phosphate binder lowers serum phosphorus and serum parathyroid hormone. The RenaGel Study Group. Kidney Int. 1999; 55: 299-307.
  56. Bleyer A.J., Burke S.K., Dillon M., et al. A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients. Am. J. Kidney Dis. 1999; 33(4): 694-701.
  57. Hutchison A.J., Speake M., Al-Baaj F. Reducing high phosphate levels in patients with chronic renal failure undergoing dialysis:a 4-week, dose-finding, open-label study with lanthanum carbonate. Nephrol Dial. Transplant. 2004;19:1902-1906.
  58. Finn W.F., Joy M.S., Hladik G.; Lanthanum Study Group. Efficacy and safety of lanthanum carbonate for reduction of serum phosphorus in patients with chronic renal failure receiving hemodialysis. Clin. Nephrol. 2004; 62: 193-201.
  59. Sprague S.M. A comparative review of the efficacy and safety of established phosphate binders: calcium, sevelamer, and lanthanum carbonate. Curr. Med. Res. Opin. 2007; 23: 3167-3175.
  60. Zhang C., Wen J., Li Z., Fan J. Efficacy and safety of lanthanum carbonate on chronic kidney disease-mineral and bone disorder in dialysis patients: a systematic review. BMC Nephrol. 2013; 4: 226. doi: 10.1186/1471-2369-14-226.
  61. D’Haese P.C., Spasovski G.B., Sikole A., et al. A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients. Kidney Int. Suppl. 2003;63:S73.
  62. Malluche H.H., Siami G.A, Swanepoel C., et al.; SPD405-307 Lanthanum Carbonate Study Group. Improvements in renal osteodystrophy in patients treated with lanthanum carbonate for two years. Clin. Nephrol. 2008;70:284-295.
  63. Haratake J., Yasunaga C., Ootani A., et al. Peculiar histiocytic lesions with massive lanthanum deposition in dialysis patients treated with lanthanum carbonate. Am. J. Surg. Pathol. 2015; 39: 767-771. doi: 10.1097/PAS.0000000000000385.
  64. Wilhelm M., Gaillard S., Rakov V., Funk F. The iron-based phosphate binder PA21 has potent phosphate binding capacity and minimal iron release across a physiological pH range in vitro. Clin. Nephrol. 2014; 81: 251-258.
  65. Phan O., Maillard M., Funk F., et al. Effect of Pa21, a new ton-based phosphate binder on fibroblast growth factor 23 (Fgf23) and vascular calcification in uremic rats. J. Hypertens. 2015; 33(1): e16-e17. doi: 10.1097/01.hjh.0000467394.66592.05.
  66. Wuthrich R.P., Chonchol M., Covic A., et al. Randomized clinical trial of the ton-based phosphate binder PA21 in hemodialysis patients. Clin. J. Am. Soc. Nephrol. 2013; 8: 280-289. doi: 10.2215/CJN.08230811.
  67. Floege J., Covic A.C., Ketteler M., et al.; PA21 Study Group. A phase III study of the efficacy and safety of a novel ton-based phosphate binder in dialysis patients. Kidney Int. 2014; 86: 638-647. doi: 10.1038/ki.2014.58.
  68. Floege J., Covic A.C., Ketteler M., et al.; Sucroferric Oxyhydroxide Study Group. Long-term effects of iron-based phosphate binder, sucroferric oxyhydroxide, in dialysis patients. Nephrol. Dial. Transplant. 2015301037-1046. doi: 10.1093/ndt/gfv006.
  69. Parameswaran V., Ficociello L.H., Van Zandt C.R., et al. Pill Burden and Serum Phosphorus in Hemodialysis Patients Switched from Sevelamer to Sucroferric Oxyhydroxide. J.Am. Soc. Nephrol. 201627FR-PO 428.
  70. Sprague S.M., Covic A.C.,-Floege J., et al. Pharmacodynamic effects of sucroferric oxyhydroxide and sevelamer carbonate on vitamin d receptor agonist bioactivity in dialysis patients. Am. J. Nephrol. 2016;44:104-112. doi: 10.1159/000447600.
  71. Yaguchi A., Yonekubo S., Maruyama I., et al. Comparison of Phosphate Binding Capacities of PA21, a novel phosphate binder, with those of other phosphate binders in vitro and in vivo. Drug Res. 2016; 66(5): 262-269. doi: 10.1055/s-0035-1569328.
  72. Dwyer J.P., Sika M., Schulman G., et al.; Collaborative Study Group. Dose-response and efficacy of ferric citrate to treat hyperphosphatemia in hemodialysis patients:a short-term randomized trial. Am. J. Kidney Dis. 2013; 61: 759-766. doi: 10.1053/j.ajkd.2012.11.041.
  73. Van Buren P.N., Lewis J.B., Dwyer J.P., et al.; Collaborative Study Group. The phosphate binder ferric citrate and mineral metabolism and inflammatory markers in maintenance dialysis patients: results from prespecified analyses of a randomized clinical trial. Am. J. Kidney Dis. 2015; 66: 479-488. doi: 10.1053/j.ajkd.2015.03.013.
  74. Lewis J., Sika M., Koury M., et al.; Collaborative Study Group. Ferric citrate controls phosphorus and delivers iron in dialysis patients. J. Am. Soc. Nephrol. 2015; 26: 493-503. doi: 10.1681/ASN.2014020212.
  75. Cheng S.C., Young D.O., Huang Y., Delmez J.A., Coyne D.W. A randomized, double-blind, placebocontrolled tial of niacinamide for reduction of phos-phorus in hemodialysis patients. Clin. J. Am. Soc. Nephrol. 2008;3:1131-1138. doi: 10.2215/CJN.04211007.
  76. Block G.A, Persky M.S., Shamblin B.M., et al. Effect of salivary phosphate-binding chewinggum on serum phosphate in chronic kidney dis-ease. Nephron. Clin. Pract. 2013;123:93-101. doi: 10.1159/000351850.

Supplementary files

Supplementary Files
Action
1. JATS XML

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies