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Treatment of hyperphosphatemia in chronic kidney disease

INTRODUCTION

The tendency toward phosphate retention develops early in renal disease due to the reduction in the filtered phosphate load. Overt hyperphosphatemia develops when the glomerular filtration rate (GFR) falls below 25 to 40 mL/min per 1.73 [1-3]. (See "Lipid abnormalities in patients with chronic kidney disease not requiring dialysis".)

Hyperphosphatemia alone or in combination with a high serum calcium has been associated with increased mortality in dialysis patients [4,5]. (See "Patient survival and maintenance dialysis", section on 'Disorders of mineral metabolism'.) This association has also been observed in some [6-8], though not all [9,10], studies of patients with less advanced kidney disease. Hyperphosphatemia may also cause significant morbidity [11,12]. (See "Vascular calcification in chronic kidney disease" and "Calciphylaxis (calcific uremic arteriolopathy)".)

Common treatment options for hyperphosphatemia include dietary phosphate restriction and oral phosphate binders and, for dialysis patients, increased dialysis. This topic reviews recommendations regarding target phosphate concentration and treatment options for hyperphosphatemia for chronic kidney disease (CKD) patients.

Recommended goals for serum parathyroid hormone (PTH) concentration for patients with CKD are discussed elsewhere. (See "Management of secondary hyperparathyroidism and mineral metabolism abnormalities in adult predialysis patients with chronic kidney disease", section on 'Goal target levels' and "Management of secondary hyperparathyroidism and mineral metabolism abnormalities in dialysis patients", section on 'Goals of therapy'.)

Mechanisms underlying the physiologic response to phosphate retention are discussed elsewhere. (See "Overview of chronic kidney disease-mineral bone disease (CKD-MBD)".)

                               

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Literature review current through: Oct 2014. | This topic last updated: Nov 19, 2014.
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References
Top
  1. Slatopolsky E, Robson AM, Elkan I, Bricker NS. Control of phosphate excretion in uremic man. J Clin Invest 1968; 47:1865.
  2. 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.
  3. Tonelli M. Serum phosphorus in people with chronic kidney disease: you are what you eat. Kidney Int 2013; 84:871.
  4. Stevens LA, Djurdjev O, Cardew S, et al. Calcium, phosphate, and parathyroid hormone levels in combination and as a function of dialysis duration predict mortality: evidence for the complexity of the association between mineral metabolism and outcomes. J Am Soc Nephrol 2004; 15:770.
  5. Young EW, Akiba T, Albert JM, et al. Magnitude and impact of abnormal mineral metabolism in hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2004; 44:34.
  6. Kestenbaum B, Sampson JN, Rudser KD, et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 2005; 16:520.
  7. Kovesdy CP, Anderson JE, Kalantar-Zadeh K. Outcomes associated with serum phosphorus level in males with non-dialysis dependent chronic kidney disease. Clin Nephrol 2010; 73:268.
  8. Voormolen N, Noordzij M, Grootendorst DC, et al. High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients. Nephrol Dial Transplant 2007; 22:2909.
  9. Mehrotra R, Peralta CA, Chen SC, et al. No independent association of serum phosphorus with risk for death or progression to end-stage renal disease in a large screen for chronic kidney disease. Kidney Int 2013; 84:989.
  10. Menon V, Greene T, Pereira AA, et al. Relationship of phosphorus and calcium-phosphorus product with mortality in CKD. Am J Kidney Dis 2005; 46:455.
  11. Delmez JA, Slatopolsky E. Hyperphosphatemia: its consequences and treatment in patients with chronic renal disease. Am J Kidney Dis 1992; 19:303.
  12. Milliner DS, Zinsmeister AR, Lieberman E, Landing B. Soft tissue calcification in pediatric patients with end-stage renal disease. Kidney Int 1990; 38:931.
  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 Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 2009; :S1.
  14. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl 2013; 3:5.
  15. Eddington H, Hoefield R, Sinha S, et al. Serum phosphate and mortality in patients with chronic kidney disease. Clin J Am Soc Nephrol 2010; 5:2251.
  16. Palmer SC, Hayen A, Macaskill P, et al. Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis. JAMA 2011; 305:1119.
  17. Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 1998; 31:607.
  18. Block GA, Klassen PS, Lazarus JM, et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004; 15:2208.
  19. Block G, Port FK. Calcium phosphate metabolism and cardiovascular disease in patients with chronic kidney disease. Semin Dial 2003; 16:140.
  20. Marco MP, Craver L, Betriu A, et al. Higher impact of mineral metabolism on cardiovascular mortality in a European hemodialysis population. Kidney Int Suppl 2003; :S111.
  21. Rodriguez-Benot A, Martin-Malo A, Alvarez-Lara MA, et al. Mild hyperphosphatemia and mortality in hemodialysis patients. Am J Kidney Dis 2005; 46:68.
  22. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003; 42:S1.
  23. Sullivan C, Sayre SS, Leon JB, et al. Effect of food additives on hyperphosphatemia among patients with end-stage renal disease: a randomized controlled trial. JAMA 2009; 301:629.
  24. Uribarri J, Calvo MS. Hidden sources of phosphorus in the typical American diet: does it matter in nephrology? Semin Dial 2003; 16:186.
  25. Zeller K, Whittaker E, Sullivan L, et al. Effect of restricting dietary protein on the progression of renal failure in patients with insulin-dependent diabetes mellitus. N Engl J Med 1991; 324:78.
  26. Lafage MH, Combe C, Fournier A, Aparicio M. Ketodiet, physiological calcium intake and native vitamin D improve renal osteodystrophy. Kidney Int 1992; 42:1217.
  27. Lafage-Proust MH, Combe C, Barthe N, Aparicio M. Bone mass and dynamic parathyroid function according to bone histology in nondialyzed uremic patients after long-term protein and phosphorus restriction. J Clin Endocrinol Metab 1999; 84:512.
  28. Emmett M. A comparison of clinically useful phosphorus binders for patients with chronic kidney failure. Kidney Int Suppl 2004; :S25.
  29. Friedman EA. An introduction to phosphate binders for the treatment of hyperphosphatemia in patients with chronic kidney disease. Kidney Int Suppl 2005; :S2.
  30. Block GA, Wheeler DC, Persky MS, et al. Effects of phosphate binders in moderate CKD. J Am Soc Nephrol 2012; 23:1407.
  31. Drüeke TB, Massy ZA. Phosphate binders in CKD: bad news or good news? J Am Soc Nephrol 2012; 23:1277.
  32. Kovesdy CP, Kuchmak O, Lu JL, Kalantar-Zadeh K. Outcomes associated with phosphorus binders in men with non-dialysis-dependent CKD. Am J Kidney Dis 2010; 56:842.
  33. Jindal K, Chan CT, Deziel C, et al. Hemodialysis clinical practice guidelines for the Canadian Society of Nephrology. J Am Soc Nephrol 2006; 17:S1.
  34. Lynch KE, Lynch R, Curhan GC, Brunelli SM. Prescribed dietary phosphate restriction and survival among hemodialysis patients. Clin J Am Soc Nephrol 2011; 6:620.
  35. Isakova T, Gutiérrez OM, Chang Y, et al. Phosphorus binders and survival on hemodialysis. J Am Soc Nephrol 2009; 20:388.
  36. Cannata-Andía JB, Fernández-Martín JL, Locatelli F, et al. Use of phosphate-binding agents is associated with a lower risk of mortality. Kidney Int 2013; 84:998.
  37. 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.
  38. Sadek T, Mazouz H, Bahloul H, et al. Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study. Nephrol Dial Transplant 2003; 18:582.
  39. Block GA, Spiegel DM, Ehrlich J, et al. Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int 2005; 68:1815.
  40. 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. 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.
  42. Tonelli M, Wiebe N, Culleton B, et al. Systematic review of the clinical efficacy and safety of sevelamer in dialysis patients. Nephrol Dial Transplant 2007; 22:2856.
  43. Shaheen FA, Akeel NM, Badawi LS, Souqiyyeh MZ. Efficacy and safety of sevelamer. Comparison with calcium carbonate in the treatment of hyperphosphatemia in hemodialysis patients. Saudi Med J 2004; 25:785.
  44. St Peter WL, Liu J, Weinhandl E, Fan Q. A comparison of sevelamer and calcium-based phosphate binders on mortality, hospitalization, and morbidity in hemodialysis: a secondary analysis of the Dialysis Clinical Outcomes Revisited (DCOR) randomized trial using claims data. Am J Kidney Dis 2008; 51:445.
  45. Wilson R, Zhang P, Smyth M, Pratt R. Assessment of survival in a 2-year comparative study of lanthanum carbonate versus standard therapy. Curr Med Res Opin 2009; 25:3021.
  46. Jamal SA, 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 meta-analysis. Lancet 2013; 382:1268.
  47. Di Iorio B, Bellasi A, Russo D, INDEPENDENT Study Investigators. Mortality in kidney disease patients treated with phosphate binders: a randomized study. Clin J Am Soc Nephrol 2012; 7:487.
  48. Chertow GM, Raggi P, Chasan-Taber S, et al. Determinants of progressive vascular calcification in haemodialysis patients. Nephrol Dial Transplant 2004; 19:1489.
  49. Fournier A, Morinière P, Ben Hamida F, et al. Use of alkaline calcium salts as phosphate binder in uremic patients. Kidney Int Suppl 1992; 38:S50.
  50. Slatopolsky E, Weerts C, Lopez-Hilker S, et al. Calcium carbonate as a phosphate binder in patients with chronic renal failure undergoing dialysis. N Engl J Med 1986; 315:157.
  51. Slatopolsky E, Weerts C, Norwood K, et al. Long-term effects of calcium carbonate and 2.5 mEq/liter calcium dialysate on mineral metabolism. Kidney Int 1989; 36:897.
  52. Mai ML, Emmett M, Sheikh MS, et al. Calcium acetate, an effective phosphorus binder in patients with renal failure. Kidney Int 1989; 36:690.
  53. Delmez JA, Tindira CA, Windus DW, et al. Calcium acetate as a phosphorus binder in hemodialysis patients. J Am Soc Nephrol 1992; 3:96.
  54. Morinière P, Djerad M, Boudailliez B, et al. Control of predialytic hyperphosphatemia by oral calcium acetate and calcium carbonate. Comparable efficacy for half the dose of elemental calcium given as acetate without lower incidence of hypercalcemia. Nephron 1992; 60:6.
  55. Meric F, Yap P, Bia MJ. Etiology of hypercalcemia in hemodialysis patients on calcium carbonate therapy. Am J Kidney Dis 1990; 16:459.
  56. Kurz P, Monier-Faugere MC, Bognar B, et al. Evidence for abnormal calcium homeostasis in patients with adynamic bone disease. Kidney Int 1994; 46:855.
  57. Goodman WG, Goldin J, Kuizon BD, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000; 342:1478.
  58. Block GA, Port FK. Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: recommendations for a change in management. Am J Kidney Dis 2000; 35:1226.
  59. Reynolds JL, Joannides AJ, Skepper JN, et al. Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD. J Am Soc Nephrol 2004; 15:2857.
  60. Ewence AE, Bootman M, Roderick HL, et al. Calcium phosphate crystals induce cell death in human vascular smooth muscle cells: a potential mechanism in atherosclerotic plaque destabilization. Circ Res 2008; 103:e28.
  61. Delmez J, Block G, Robertson J, et al. A randomized, double-blind, crossover design study of sevelamer hydrochloride and sevelamer carbonate in patients on hemodialysis. Clin Nephrol 2007; 68:386.
  62. Chertow GM, Burke SK, Lazarus JM, et al. Poly[allylamine hydrochloride] (RenaGel): a noncalcemic phosphate binder for the treatment of hyperphosphatemia in chronic renal failure. Am J Kidney Dis 1997; 29:66.
  63. Goldberg DI, Dillon MA, Slatopolsky EA, et al. Effect of RenaGel, a non-absorbed, calcium- and aluminium-free phosphate binder, on serum phosphorus, calcium, and intact parathyroid hormone in end-stage renal disease patients. Nephrol Dial Transplant 1998; 13:2303.
  64. Slatopolsky EA, Burke SK, Dillon MA. RenaGel, a nonabsorbed calcium- and aluminum-free phosphate binder, lowers serum phosphorus and parathyroid hormone. The RenaGel Study Group. Kidney Int 1999; 55:299.
  65. Chertow GM, Dillon M, Burke SK, et al. A randomized trial of sevelamer hydrochloride (RenaGel) with and without supplemental calcium. Strategies for the control of hyperphosphatemia and hyperparathyroidism in hemodialysis patients. Clin Nephrol 1999; 51:18.
  66. Bleyer AJ, Burke SK, 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; 33:694.
  67. Ogata H, Koiwa F, Shishido K, Kinugasa E. Combination therapy with sevelamer hydrochloride and calcium carbonate in Japanese patients with long-term hemodialysis: alternative approach for optimal mineral management. Ther Apher Dial 2005; 9:11.
  68. Fischer D, Cline K, Plone MA, et al. Results of a randomized crossover study comparing once-daily and thrice-daily sevelamer dosing. Am J Kidney Dis 2006; 48:437.
  69. Ketteler M, Rix M, Fan S, et al. Efficacy and tolerability of sevelamer carbonate in hyperphosphatemic patients who have chronic kidney disease and are not on dialysis. Clin J Am Soc Nephrol 2008; 3:1125.
  70. Manns B, Stevens L, Miskulin D, et al. A systematic review of sevelamer in ESRD and an analysis of its potential economic impact in Canada and the United States. Kidney Int 2004; 66:1239.
  71. Manns B, Klarenbach S, Lee H, et al. Economic evaluation of sevelamer in patients with end-stage renal disease. Nephrol Dial Transplant 2007; 22:2867.
  72. Joy MS, Finn WF, LAM-302 Study Group. Randomized, double-blind, placebo-controlled, dose-titration, phase III study assessing the efficacy and tolerability of lanthanum carbonate: a new phosphate binder for the treatment of hyperphosphatemia. Am J Kidney Dis 2003; 42:96.
  73. Hutchison AJ, 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.
  74. Finn WF, Joy MS, 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.
  75. Behets GJ, Verberckmoes SC, D'Haese PC, De Broe ME. Lanthanum carbonate: a new phosphate binder. Curr Opin Nephrol Hypertens 2004; 13:403.
  76. Hutchison AJ, Maes B, Vanwalleghem J, et al. Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomized, comparative trial versus calcium carbonate. Nephron Clin Pract 2005; 100:c8.
  77. Chiang SS, Chen JB, Yang WC. Lanthanum carbonate (Fosrenol) efficacy and tolerability in the treatment of hyperphosphatemic patients with end-stage renal disease. Clin Nephrol 2005; 63:461.
  78. Finn WF, SPD 405-307 Lanthanum Study Group. Lanthanum carbonate versus standard therapy for the treatment of hyperphosphatemia: safety and efficacy in chronic maintenance hemodialysis patients. Clin Nephrol 2006; 65:191.
  79. Persy VP, Behets GJ, Bervoets AR, et al. Lanthanum: a safe phosphate binder. Semin Dial 2006; 19:195.
  80. Sprague SM, Abboud H, Qiu P, et al. Lanthanum carbonate reduces phosphorus burden in patients with CKD stages 3 and 4: a randomized trial. Clin J Am Soc Nephrol 2009; 4:178.
  81. D'Haese PC, Spasovski GB, 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; :S73.
  82. Freemont T, Malluche HH. Utilization of bone histomorphometry in renal osteodystrophy: demonstration of a new approach using data from a prospective study of lanthanum carbonate. Clin Nephrol 2005; 63:138.
  83. Altmann P, Barnett ME, Finn WF, SPD405-307 Lanthanum Carbonate Study Group. Cognitive function in Stage 5 chronic kidney disease patients on hemodialysis: no adverse effects of lanthanum carbonate compared with standard phosphate-binder therapy. Kidney Int 2007; 71:252.
  84. Mehrotra R, Martin KJ, Fishbane S, et al. Higher strength lanthanum carbonate provides serum phosphorus control with a low tablet burden and is preferred by patients and physicians: a multicenter study. Clin J Am Soc Nephrol 2008; 3:1437.
  85. Behets GJ, Dams G, Vercauteren SR, et al. Does the phosphate binder lanthanum carbonate affect bone in rats with chronic renal failure? J Am Soc Nephrol 2004; 15:2219.
  86. Lacour B, Lucas A, Auchère D, et al. Chronic renal failure is associated with increased tissue deposition of lanthanum after 28-day oral administration. Kidney Int 2005; 67:1062.
  87. Slatopolsky E, Liapis H, Finch J. Progressive accumulation of lanthanum in the liver of normal and uremic rats. Kidney Int 2005; 68:2809.
  88. Aime S, Canavese C, Stratta P. Advisory about gadolinium calls for caution in the treatment of uremic patients with lanthanum carbonate. Kidney Int 2007; 72:1162.
  89. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails (Accessed on February 28, 2014).
  90. Wüthrich RP, Chonchol M, Covic A, et al. Randomized clinical trial of the iron-based phosphate binder PA21 in hemodialysis patients. Clin J Am Soc Nephrol 2013; 8:280.
  91. Floege J, Covic AC, Ketteler M, et al. A phase III study of the efficacy and safety of a novel iron-based phosphate binder in dialysis patients. Kidney Int 2014; 86:638.
  92. Yokoyama K, Hirakata H, Akiba T, et al. Ferric citrate hydrate for the treatment of hyperphosphatemia in nondialysis-dependent CKD. Clin J Am Soc Nephrol 2014; 9:543.
  93. Müller D, Mehling H, Otto B, et al. Niacin lowers serum phosphate and increases HDL cholesterol in dialysis patients. Clin J Am Soc Nephrol 2007; 2:1249.
  94. Cheng SC, Young DO, Huang Y, et al. A randomized, double-blind, placebo-controlled trial of niacinamide for reduction of phosphorus in hemodialysis patients. Clin J Am Soc Nephrol 2008; 3:1131.
  95. Molitoris BA, Froment DH, Mackenzie TA, et al. Citrate: a major factor in the toxicity of orally administered aluminum compounds. Kidney Int 1989; 36:949.
  96. Nolan CR, Califano JR, Butzin CA. Influence of calcium acetate or calcium citrate on intestinal aluminum absorption. Kidney Int 1990; 38:937.
  97. Kirschbaum BB, Schoolwerth AC. Acute aluminum toxicity associated with oral citrate and aluminum-containing antacids. Am J Med Sci 1989; 297:9.
  98. Schiller LR, Santa Ana CA, Sheikh MS, et al. Effect of the time of administration of calcium acetate on phosphorus binding. N Engl J Med 1989; 320:1110.