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Phosphate binders in chronic kidney disease: a systematic review of recent data

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Abstract

Hyperphosphatemia is common in chronic kidney disease (CKD) and is treated by dietary measures, dialysis techniques and/or phosphate binders. For the present review PubMed was searched for new publications on phosphate binders appearing between January 2010 and October 2015. This review summarizes the latest information on non-pharmacological measures and their problems in lowering phosphate in CKD patients, effects of phosphate binders on morbidity and mortality, adherence to phosphate binder therapy as well as new information on specific aspects of the various phosphate binders on the market: calcium acetate, calcium carbonate, magnesium-containing phosphate binders, polymeric phosphate binders (sevelamer, bixalomer, colestilan), lanthanum carbonate, ferric citrate, sucroferric oxyhydroxide, aluminum-containing phosphate binders, and new compounds in development. The review also briefly covers the emerging field of drugs targeting intestinal phosphate transporters.

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References

  1. Tonelli M, Pannu N, Manns B (2010) Oral phosphate binders in patients with kidney failure. N Engl J Med 362:1312–1324

    Article  CAS  PubMed  Google Scholar 

  2. Mehrotra R, Peralta CA, Chen SC, Li S, Sachs M, Shah A, Norris K, Saab G, Whaley-Connell A, Kestenbaum B, McCullough PA, Kidney early evaluation program I (2013) 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 84:989–997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Shanahan CM, Crouthamel MH, Kapustin A, Giachelli CM (2011) Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res 109:697–711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Abbasian N, Burton JO, Herbert KE, Tregunna BE, Brown JR, Ghaderi-Najafabadi M, Brunskill NJ, Goodall AH, Bevington A (2015) Hyperphosphatemia, phosphoprotein phosphatases, and microparticle release in vascular endothelial cells. J Am Soc Nephrol 26:2152–2162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Shobeiri N, Adams MA, Holden RM (2014) Phosphate: an old bone molecule but new cardiovascular risk factor. Br J Clin Pharmacol 77:39–54

    Article  CAS  PubMed  Google Scholar 

  6. Cunningham J, Locatelli F, Rodriguez M (2011) Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol 6:913–921

    Article  CAS  PubMed  Google Scholar 

  7. Nagel CJ, Casal MC, Lindley E, Rogers S, Pancirova J, Kernc J, Copley JB, Fouque D (2014) Management of hyperphosphataemia: practices and perspectives amongst the renal care community. J Ren Care 40:230–238

    Article  PubMed  Google Scholar 

  8. Cupisti A, Benini O, Ferretti V, Gianfaldoni D, Kalantar-Zadeh K (2012) Novel differential measurement of natural and added phosphorus in cooked ham with or without preservatives. J Ren Nutr 22:533–540

    Article  CAS  PubMed  Google Scholar 

  9. Penne EL, van der Weerd NC, van den Dorpel MA, Grooteman MP, Levesque R, Nube MJ, Bots ML, Blankestijn PJ, ter Wee PM, Investigators C (2010) Short-term effects of online hemodiafiltration on phosphate control: a result from the randomized controlled Convective Transport Study (CONTRAST). Am J Kidney Dis 55:77–87

    Article  CAS  PubMed  Google Scholar 

  10. Kuhlmann MK (2010) Phosphate elimination in modalities of hemodialysis and peritoneal dialysis. Blood Purif 29:137–144

    Article  CAS  PubMed  Google Scholar 

  11. Daugirdas JT, Chertow GM, Larive B, Pierratos A, Greene T, Ayus JC, Kendrick CA, James SH, Miller BW, Schulman G, Salusky IB, Kliger AS, Frequent Hemodialysis Network Trial G (2012) Effects of frequent hemodialysis on measures of CKD mineral and bone disorder. J Am Soc Nephrol 23:727–738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Movilli E, Camerini C, Gaggia P, Poiatti P, Pola A, Viola BF, Zubani R, Jeannin G, Cancarini G (2011) Effect of post-dilutional on-line haemodiafiltration on serum calcium, phosphate and parathyroid hormone concentrations in uraemic patients. Nephrol Dial Transpl 26:4032–4037

    Article  CAS  Google Scholar 

  13. Locatelli F, Altieri P, Andrulli S, Sau G, Bolasco P, Pedrini LA, Basile C, David S, Gazzanelli L, Tampieri G, Isola E, Marzolla O, Memoli B, Ganadu M, Reina E, Bertoli S, Ferrara R, Casu D, Logias F, Tarchini R, Mattana G, Passaghe M, Fundoni G, Villa G, Di Iorio BR, Pontoriero G, Zoccali C (2014) 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 Transpl 29:1239–1246

    Article  CAS  Google Scholar 

  14. Zitt E, Fouque D, Jacobson SH, Malberti F, Ryba M, Urena P, Rix M, Dehmel B, Manamley N, Vervloet M (2013) Serum phosphorus reduction in dialysis patients treated with cinacalcet for secondary hyperparathyroidism results mainly from parathyroid hormone reduction. Clin Kidney J 6:287–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Denburg MR, Kumar J, Jemielita T, Brooks ER, Skversky A, Portale AA, Salusky IB, Warady BA, Furth SL, Leonard MB (2015) Fracture burden and risk factors in childhood CKD: results from the CKiD cohort study. J Am Soc Nephrol ASN-2015020152 [Epub ahead of print]

  16. Kovesdy CP, Kuchmak O, Lu JL, Kalantar-Zadeh K (2010) Outcomes associated with phosphorus binders in men with non-dialysis-dependent CKD. Am J Kidney Dis 56:842–851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cannata-Andia JB, Fernandez-Martin JL, Locatelli F, London G, Gorriz JL, Floege J, Ketteler M, Ferreira A, Covic A, Rutkowski B, Memmos D, Bos WJ, Teplan V, Nagy J, Tielemans C, Verbeelen D, Goldsmith D, Kramar R, Martin PY, Wuthrich RP, Pavlovic D, Benedik M, Sanchez JE, Martinez-Camblor P, Naves-Diaz M, Carrero JJ, Zoccali C (2013) Use of phosphate-binding agents is associated with a lower risk of mortality. Kidney Int 84:998–1008

    Article  CAS  PubMed  Google Scholar 

  18. Lopes AA, Tong L, Thumma J, Li Y, Fuller DS, Morgenstern H, Bommer J, Kerr PG, Tentori F, Akiba T, Gillespie BW, Robinson BM, Port FK, Pisoni RL (2012) 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 60:90–101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Smith ER (2014) The use of fibroblast growth factor 23 testing in patients with kidney disease. Clin J Am Soc Nephrol 9:1283–1303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Moe SM, Chertow GM, Parfrey PS, Kubo Y, Block GA, Correa-Rotter R, Drueke TB, Herzog CA, London GM, Mahaffey KW, Wheeler DC, Stolina M, Dehmel B, Goodman WG, Floege J (2015) Evaluation of cinacalcet HTtLCETI: cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis: the evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial. Circulation 132:27–39

    Article  CAS  PubMed  Google Scholar 

  21. Block GA, Wheeler DC, Persky MS, Kestenbaum B, Ketteler M, Spiegel DM, Allison MA, Asplin J, Smits G, Hoofnagle AN, Kooienga L, Thadhani R, Mannstadt M, Wolf M, Chertow GM (2012) Effects of phosphate binders in moderate CKD. J Am Soc Nephrol 23:1407–1415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Van Camp YP, Vrijens B, Abraham I, Van Rompaey B, Elseviers MM (2014) Adherence to phosphate binders in hemodialysis patients: prevalence and determinants. J Nephrol 27(6):673–679

  23. Covic A, Rastogi A (2013) Hyperphosphatemia in patients with ESRD: assessing the current evidence linking outcomes with treatment adherence. BMC Nephrol 14:153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wileman V, Farrington K, Wellsted D, Almond M, Davenport A, Chilcot J (2015) Medication beliefs are associated with phosphate binder non-adherence in hyperphosphatemic haemodialysis patients. Br J Health Psychol 20:563–578

    Article  PubMed  Google Scholar 

  25. Arenas MD, Malek T, Gil MT, Moledous A, Alvarez-Ude F, Reig-Ferrer A (2010) Challenge of phosphorus control in hemodialysis patients: a problem of adherence? J Nephrol 23:525–534

    PubMed  Google Scholar 

  26. Fouque D, Horne R, Cozzolino M, Kalantar-Zadeh K (2014) Balancing nutrition and serum phosphorus in maintenance dialysis. Am J Kidney Dis 64:143–150

    Article  CAS  PubMed  Google Scholar 

  27. Shi YX, Fan XY, Han HJ, Wu QX, Di HJ, Hou YH, Zhao Y (2013) Effectiveness of a nurse-led intensive educational programme on chronic kidney failure patients with hyperphosphataemia: randomised controlled trial. J Clin Nurs 22:1189–1197

    Article  PubMed  Google Scholar 

  28. Van Camp YP, Huybrechts SA, Van Rompaey B, Elseviers MM (2012) Nurse-led education and counselling to enhance adherence to phosphate binders. J Clin Nurs 21:1304–1313

    Article  PubMed  Google Scholar 

  29. Umeukeje EM, Merighi JR, Browne T, Victoroff JN, Umanath K, Lewis JB, Ikizler TA, Wallston KA, Cavanaugh K (2015) Self-motivation is associated with phosphorus control in end-stage renal disease. J Ren Nutr 25:433–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jamal SA, Moe SM (2012) Calcium builds strong bones, and more is better–correct? Well, maybe not. Clin J Am Soc Nephrol 7:1877–1883

    Article  PubMed  Google Scholar 

  31. West SL, Swan VJ, Jamal SA (2010) Effects of calcium on cardiovascular events in patients with kidney disease and in a healthy population. Clin J Am Soc Nephrol 5(Suppl 1):S41–S47

    Article  CAS  PubMed  Google Scholar 

  32. Winkelmayer WC, Liu J, Kestenbaum B (2011) Comparative effectiveness of calcium-containing phosphate binders in incident US dialysis patients. Clin J Am Soc Nephrol 6:175–183

    Article  PubMed  PubMed Central  Google Scholar 

  33. Jamal SA, Vandermeer B, Raggi P, Mendelssohn DC, Chatterley T, Dorgan M, Lok CE, Fitchett D, Tsuyuki RT (2013) 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 382:1268–1277

    Article  CAS  PubMed  Google Scholar 

  34. Jean G, Lataillade D, Genet L, Legrand E, Kuentz F, Moreau-Gaudry X, Fouque D, investigators As (2011) Calcium carbonate, but not sevelamer, is associated with better outcomes in hemodialysis patients: results from the French ARNOS study. Hemodial Int 15:485–492

    Article  PubMed  Google Scholar 

  35. Hill KM, Martin BR, Wastney ME, McCabe GP, Moe SM, Weaver CM, Peacock M (2013) Oral calcium carbonate affects calcium but not phosphorus balance in stage 3–4 chronic kidney disease. Kidney Int 83:959–966

    Article  CAS  PubMed  Google Scholar 

  36. Spiegel DM, Brady K (2012) Calcium balance in normal individuals and in patients with chronic kidney disease on low- and high-calcium diets. Kidney Int 81:1116–1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Shroff RC, McNair R, Skepper JN, Figg N, Schurgers LJ, Deanfield J, Rees L, Shanahan CM (2010) Chronic mineral dysregulation promotes vascular smooth muscle cell adaptation and extracellular matrix calcification. J Am Soc Nephrol 21:103–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hutchison AJ, Wilkie M (2012) Use of magnesium as a drug in chronic kidney disease. Clin Kidney J 5:i62–i70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. de Francisco AL, Leidig M, Covic AC, Ketteler M, Benedyk-Lorens E, Mircescu GM, Scholz C, Ponce P, Passlick-Deetjen J (2010) 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 Transpl 25:3707–3717

    Article  CAS  Google Scholar 

  40. Evsanaa B, Liu I, Aliazardeh B, Mahdavi S, Bajwa G, Gula J, Tam M, Sze E, Roscoe JM, Tam PY, Sikaneta T (2015) MgCaCO3 versus CaCO3 in peritoneal dialysis patients—a cross-over pilot trial. Perit Dial Int 35:31–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Tzanakis IP, Stamataki EE, Papadaki AN, Giannakis N, Damianakis NE, Oreopoulos DG (2014) Magnesium retards the progress of the arterial calcifications in hemodialysis patients: a pilot study. Int Urol Nephrol 46:2199–2205

    Article  CAS  PubMed  Google Scholar 

  42. De Schutter TM, Behets GJ, Geryl H, Peter ME, Steppan S, Gundlach K, Passlick-Deetjen J, D’Haese PC, Neven E (2013) Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia. Kidney Int 83:1109–1117

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Di Iorio B, Molony D, Bell C, Cucciniello E, Bellizzi V, Russo D, Bellasi A, Investigators IS (2013) Sevelamer versus calcium carbonate in incident hemodialysis patients: results of an open-label 24-month randomized clinical trial. Am J Kidney Dis 62:771–778

    Article  PubMed  CAS  Google Scholar 

  44. Di Iorio B, Bellasi A, Russo D, Investigators IS (2012) Mortality in kidney disease patients treated with phosphate binders: a randomized study. Clin J Am Soc Nephrol 7:487–493

    Article  PubMed  CAS  Google Scholar 

  45. Iimori S, Mori Y, Akita W, Takada S, Kuyama T, Ohnishi T, Shikuma S, Ishigami J, Tajima M, Asai T, Okado T, Kuwahara M, Sasaki S, Tsukamoto Y (2012) Effects of sevelamer hydrochloride on mortality, lipid abnormality and arterial stiffness in hemodialyzed patients: a propensity-matched observational study. Clin Exp Nephrol 16:930–937

    Article  CAS  PubMed  Google Scholar 

  46. Suki WN, Zabaneh R, Cangiano JL, Reed J, Fischer D, Garrett L, Ling BN, Chasan-Taber S, Dillon MA, Blair AT, Burke SK (2007) Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. Kidney Int 72:1130–1137

    Article  CAS  PubMed  Google Scholar 

  47. Maizel J, Six I, Dupont S, Secq E, Dehedin B, Barreto FC, Benchitrit J, Poirot S, Slama M, Tribouilloy C, Choukroun G, Maziere JC, Drueke TB, Massy ZA (2013) Effects of sevelamer treatment on cardiovascular abnormalities in mice with chronic renal failure. Kidney Int 84:491–500

    Article  CAS  PubMed  Google Scholar 

  48. Kakuta T, Tanaka R, Hyodo T, Suzuki H, Kanai G, Nagaoka M, Takahashi H, Hirawa N, Oogushi Y, Miyata T, Kobayashi H, Fukagawa M, Saito A (2011) 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 57:422–431

    Article  CAS  PubMed  Google Scholar 

  49. Chue CD, Townend JN, Moody WE, Zehnder D, Wall NA, Harper L, Edwards NC, Steeds RP, Ferro CJ (2013) Cardiovascular effects of sevelamer in stage 3 CKD. J Am Soc Nephrol 24:842–852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Di Lullo L, Floccari F, Santoboni A, Barbera V, Rivera RF, Granata A, Morrone L, Russo D (2013) Progression of cardiac valve calcification and decline of renal function in CKD patients. J Nephrol 26:739–744

    Article  PubMed  CAS  Google Scholar 

  51. Lin YF, Chien CT, Kan WC, Chen YM, Chu TS, Hung KY, Tsai TJ, Wu KD, Wu MS (2011) Pleiotropic effects of sevelamer beyond phosphate binding in end-stage renal disease patients: a randomized, open-label, parallel-group study. Clin Drug Investig 31:257–267

    Article  PubMed  Google Scholar 

  52. Navarro-Gonzalez JF, Mora-Fernandez C, Muros de Fuentes M, Donate-Correa J, Cazana-Perez V, Garcia-Perez J (2011) Effect of phosphate binders on serum inflammatory profile, soluble CD14, and endotoxin levels in hemodialysis patients. Clin J Am Soc Nephrol 6:2272–2279

  53. Vlassara H, Uribarri J, Cai W, Goodman S, Pyzik R, Post J, Grosjean F, Woodward M, Striker GE (2012) Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products in diabetic kidney disease. Clin J Am Soc Nephrol 7:934–942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Guida B, Cataldi M, Riccio E, Grumetto L, Pota A, Borrelli S, Memoli A, Barbato F, Argentino G, Salerno G, Memoli B (2013) Plasma p-cresol lowering effect of sevelamer in peritoneal dialysis patients: evidence from a cross-sectional observational study. PLoS One 8:e73558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Brandenburg VM, Schlieper G, Heussen N, Holzmann S, Busch B, Evenepoel P, Vanholder R, Meijers B, Meert N, Fassbender WJ, Floege J, Jahnen-Dechent W, Ketteler M (2010) Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study. Nephrol Dial Transpl 25:2672–2679

    Article  CAS  Google Scholar 

  56. Takagi K, Masuda K, Yamazaki M, Kiyohara C, Itoh S, Wasaki M, Inoue H (2010) Metal ion and vitamin adsorption profiles of phosphate binder ion-exchange resins. Clin Nephrol 73:30–35

    Article  CAS  PubMed  Google Scholar 

  57. Pierce D, Hossack S, Poole L, Robinson A, Van Heusen H, Martin P, Smyth M (2011) The effect of sevelamer carbonate and lanthanum carbonate on the pharmacokinetics of oral calcitriol. Nephrol Dial Transpl 26:1615–1621

    Article  CAS  Google Scholar 

  58. Iovino M, Iovine N, Petrosino A, Giagulli VA, Licchelli B, Guastamacchia E, Triggiani V (2014) Sevelamer carbonate markedly reduces levothyroxine absorption. Endocr Metab Immune Disord Drug Targets 14:206–209

    Article  CAS  PubMed  Google Scholar 

  59. Fishbane S, Delmez J, Suki WN, Hariachar SK, Heaton J, Chasan-Taber S, Plone MA, Moe S (2010) A randomized, parallel, open-label study to compare once-daily sevelamer carbonate powder dosing with thrice-daily sevelamer hydrochloride tablet dosing in CKD patients on hemodialysis. Am J Kidney Dis 55:307–315

    Article  CAS  PubMed  Google Scholar 

  60. Tzanno-Martins C, Biavo BM, Ferreira-Filho O, Ribeiro-Junior E, Joao-Luiz MV, Degaspari S, Scavone C, Kawamoto E (2014) Clinical efficacy, safety and anti-inflammatory activity of two sevelamer tablet forms in patients on low-flux hemodialysis. Int J Immunopathol Pharmacol 27:25–35

    Article  CAS  PubMed  Google Scholar 

  61. Ito K, Takeshima A, Shishido K, Wakasa M, Kumata C, Matsuzaka K, Nakajima Y, Ogata H (2014) Treatment of hyperphosphatemia with bixalomer in Japanese patients on long-term hemodialysis with gastrointestinal symptoms. Ther Apher Dial 18(Suppl 2):19–23

    Article  CAS  PubMed  Google Scholar 

  62. Locatelli F, Dimkovic N, Spasovski G (2014) Efficacy of colestilan in the treatment of hyperphosphataemia in renal disease patients. Expert Opin Pharmacother 15:1475–1488

    Article  CAS  PubMed  Google Scholar 

  63. Locatelli F, Dimkovic N, Pontoriero G, Spasovski G, Pljesa S, Kostic S, Manning A, Sano H, Nakajima S (2010) Effect of MCI-196 on serum phosphate and cholesterol levels in haemodialysis patients with hyperphosphataemia: a double-blind, randomized, placebo-controlled study. Nephrol Dial Transpl 25:574–581

    Article  CAS  Google Scholar 

  64. Locatelli F, Dimkovic N, Spasovski G (2013) Evaluation of colestilan in chronic kidney disease dialysis patients with hyperphosphataemia and dyslipidaemia: a randomized, placebo-controlled, multiple fixed-dose trial. Nephrol Dial Transpl 28:1874–1888

    Article  CAS  Google Scholar 

  65. Locatelli F, Spasovski G, Dimkovic N, Wanner C, Dellanna F, Pontoriero G (2014) The effects of colestilan versus placebo and sevelamer in patients with CKD 5D and hyperphosphataemia: a 1-year prospective randomized study. Nephrol Dial Transpl 29:1061–1073

    Article  CAS  Google Scholar 

  66. Hertel J, Locatelli F, Spasovski G, Dimkovic N, Wanner C (2015) Randomized, double-blind, placebo-controlled, withdrawal study of colestilan after dose titration in chronic kidney disease dialysis patients with hyperphosphatemia. Nephron 130:229–238

    Article  CAS  PubMed  Google Scholar 

  67. Yubero-Serrano EM, Woodward M, Poretsky L, Vlassara H, Striker GE, Group AG-lS (2015) Effects of sevelamer carbonate on advanced glycation end products and antioxidant/pro-oxidant status in patients with diabetic kidney disease. Clin J Am Soc Nephrol 10:759–766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Vemuri N, Michelis MF, Matalon A (2011) Conversion to lanthanum carbonate monotherapy effectively controls serum phosphorus with a reduced tablet burden: a multicenter open-label study. BMC Nephrol 12:49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Dellanna F, Reichel H, Seibt F (2012) Efficacy and safety of lanthanum carbonate in German patients on dialysis. Clin Nephrol 78:382–390

    Article  CAS  PubMed  Google Scholar 

  70. Komaba H, Kakuta T, Suzuki H, Hida M, Suga T, Fukagawa M (2015) Survival advantage of lanthanum carbonate for hemodialysis patients with uncontrolled hyperphosphatemia. Nephrol Dial Transpl 30:107–114

    Article  CAS  Google Scholar 

  71. Arenas MD, Rebollo P, Malek T, Moledous A, Gil MT, Alvarez-Ude F, Morales A, Cotilla E (2010) A comparative study of 2 new phosphate binders (sevelamer and lanthanum carbonate) in routine clinical practice. J Nephrol 23:683–692

    PubMed  Google Scholar 

  72. Takahara Y, Matsuda Y, Takahashi S, Shigematsu T (2014) Lanthanum carbonate study G: efficacy and safety of lanthanum carbonate in pre-dialysis CKD patients with hyperphosphatemia: a randomized trial. Clin Nephrol 82:181–190

    Article  CAS  PubMed  Google Scholar 

  73. Gonzalez-Parra E, Gonzalez-Casaus ML, Galan A, Martinez-Calero A, Navas V, Rodriguez M, Ortiz A (2011) Lanthanum carbonate reduces FGF23 in chronic kidney disease stage 3 patients. Nephrol Dial Transpl 26:2567–2571

    Article  CAS  Google Scholar 

  74. Urena-Torres P, Prie D, Keddad K, Preston P, Wilde P, Wan H, Copley JB (2014) Changes in fibroblast growth factor 23 levels in normophosphatemic patients with chronic kidney disease stage 3 treated with lanthanum carbonate: results of the PREFECT study, a phase 2a, double blind, randomized, placebo-controlled trial. BMC Nephrol 15:71

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Zhang C, Wen J, Li Z, Fan J (2013) Efficacy and safety of lanthanum carbonate on chronic kidney disease-mineral and bone disorder in dialysis patients: a systematic review. BMC Nephrol 14:226

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Nikolov IG, Joki N, Nguyen-Khoa T, Guerrera IC, Maizel J, Benchitrit J, Machado dos Reis L, Edelman A, Lacour B, Jorgetti V, Drueke TB, Massy ZA (2012) Lanthanum carbonate, like sevelamer-HCl, retards the progression of vascular calcification and atherosclerosis in uremic apolipoprotein E-deficient mice. Nephrol Dial Transpl 27:505–513

  77. Toida T, Fukudome K, Fujimoto S, Yamada K, Sato Y, Chiyotanda S, Kitamura K (2012) Effect of lanthanum carbonate vs. calcium carbonate on serum calcium in hemodialysis patients: a crossover study. Clin Nephrol 78:216–223

    Article  CAS  PubMed  Google Scholar 

  78. Ohtake T, Kobayashi S, Oka M, Furuya R, Iwagami M, Tsutsumi D, Mochida Y, Maesato K, Ishioka K, Moriya H, Hidaka S (2013) Lanthanum carbonate delays progression of coronary artery calcification compared with calcium-based phosphate binders in patients on hemodialysis: a pilot study. J Cardiovasc Pharmacol Ther 18:439–446

    Article  CAS  PubMed  Google Scholar 

  79. Toussaint ND, Lau KK, Polkinghorne KR, Kerr PG (2011) Attenuation of aortic calcification with lanthanum carbonate versus calcium-based phosphate binders in haemodialysis: a pilot randomized controlled trial. Nephrology (Carlton) 16:290–298

    Article  CAS  Google Scholar 

  80. Shigematsu T, Tokumoto A, Nakaoka A, Arisaka H (2011) Effect of lanthanum carbonate treatment on bone in Japanese dialysis patients with hyperphosphatemia. Ther Apher Dial 15:176–184

    Article  CAS  PubMed  Google Scholar 

  81. Di Iorio B, Cucciniello E (2010) Lanthanum carbonate is not associated with QT interval modification in hemodialysis patients. Clin Pharmacol 2:89–93

    PubMed  PubMed Central  Google Scholar 

  82. Hutchison AJ, Barnett ME, Krause R, Siami GA, Lanthanum Carbonate Study G (2009) Lanthanum carbonate treatment, for up to 6 years, is not associated with adverse effects on the liver in patients with chronic kidney disease stage 5 receiving hemodialysis. Clin Nephrol 71:286–295

    CAS  PubMed  Google Scholar 

  83. Tonooka A, Uda S, Tanaka H, Yao A, Uekusa T (2015) Possibility of lanthanum absorption in the stomach. Clin Kidney J 8:572–575

    Article  PubMed  PubMed Central  Google Scholar 

  84. Hara S, Fujimori A, Nishi S (2015) Clinicopathological characteristics of lanthanum deposition in the gastrointestinal tract of dialysis patients (abstract). J Am Soc Nephrol 26:279A

    Google Scholar 

  85. Valika AH, Jain D, Jaffe PE, Moeckel G, Brewster UC (2016) A nodular foreign body reaction in a dialysis patient receiving long-term treatment with lanthanum carbonate. Am J Kidney Dis 67(1):128–32

  86. Black T, Philips G, Burbridge R (2013) Pharmacobezoar in a patient on an oral phosphate binder. Gastrointest Endosc 77:511–512

    Article  PubMed  Google Scholar 

  87. How PP, Anattiwong P, Mason DL, Arruda JA, Lau AH (2011) Phosphate-binding efficacy of crushed vs. chewed lanthanum carbonate in hemodialysis patients. Hemodial Int 15:95–99

    Article  PubMed  Google Scholar 

  88. Pierce D, Hossack S, Robinson A, Zhang P, Martin P (2012) Assessment of pharmacodynamic equivalence and tolerability of lanthanum carbonate oral powder and tablet formulations: a single-center, randomized, open-label, 2-period crossover study in healthy subjects. Clin Ther 34(1290–300):e2

    Google Scholar 

  89. Hayashi H, Machida M, Sekine T, Yamaguchi H, Kiriyama T, Kumita S (2010) Beam-hardening artifacts on computed tomography images caused by lanthanum carbonate hydrate in a patient on dialysis. Jpn J Radiol 28:322–324

    Article  PubMed  Google Scholar 

  90. Block GA, Fishbane S, Rodriguez M, Smits G, Shemesh S, Pergola PE, Wolf M, Chertow GM (2015) A 12-week, double-blind, placebo-controlled trial of ferric citrate for the treatment of iron deficiency anemia and reduction of serum phosphate in patients with CKD stages 3–5. Am J Kidney Dis 65:728–736

    Article  CAS  PubMed  Google Scholar 

  91. Yokoyama K, Hirakata H, Akiba T, Fukagawa M, Nakayama M, Sawada K, Kumagai Y, Block GA (2014) Ferric citrate hydrate for the treatment of hyperphosphatemia in nondialysis-dependent CKD. Clin J Am Soc Nephrol 9:543–552

    Article  PubMed  PubMed Central  Google Scholar 

  92. Lewis JB, Sika M, Koury MJ, Chuang P, Schulman G, Smith MT, Whittier FC, Linfert DR, Galphin CM, Athreya BP, Nossuli AK, Chang IJ, Blumenthal SS, Manley J, Zeig S, Kant KS, Olivero JJ, Greene T, Dwyer JP, Collaborative Study G (2015) Ferric citrate controls phosphorus and delivers iron in patients on dialysis. J Am Soc Nephrol 26:493–503

    Article  PubMed  CAS  Google Scholar 

  93. Umanath K, Jalal DI, Greco BA, Umeukeje EM, Reisin E, Manley J, Zeig S, Negoi DG, Hiremath AN, Blumenthal SS, Sika M, Niecestro R, Koury MJ, Ma KN, Greene T, Lewis JB, Dwyer JP, Collaborative Study G (2015) Ferric citrate reduces intravenous iron and erythropoiesis-stimulating agent use in ESRD. J Am Soc Nephrol 26:2578–2587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Lee CT, Wu IW, Chiang SS, Peng YS, Shu KH, Wu MJ, Wu MS (2015) Effect of oral ferric citrate on serum phosphorus in hemodialysis patients: multicenter, randomized, double-blind, placebo-controlled study. J Nephrol 28:105–113

    Article  CAS  PubMed  Google Scholar 

  95. Yokoyama K, Hirakata H, Akiba T, Sawada K, Kumagai Y (2012) Effect of oral JTT-751 (ferric citrate) on hyperphosphatemia in hemodialysis patients: results of a randomized, double-blind, placebo-controlled trial. Am J Nephrol 36:478–487

    Article  CAS  PubMed  Google Scholar 

  96. Yokoyama K, Akiba T, Fukagawa M, Nakayama M, Sawada K, Kumagai Y, Chertow GM, Hirakata H (2014) A randomized trial of JTT-751 versus sevelamer hydrochloride in patients on hemodialysis. Nephrol Dial Transpl 29:1053–1060

    Article  CAS  Google Scholar 

  97. Dwyer JP, Sika M, Schulman G, Chang IJ, Anger M, Smith M, Kaplan M, Zeig S, Koury MJ, Blumenthal SS, Lewis JB, Collaborative Study G (2013) Dose-response and efficacy of ferric citrate to treat hyperphosphatemia in hemodialysis patients: a short-term randomized trial. Am J Kidney Dis 61:759–766

    Article  CAS  PubMed  Google Scholar 

  98. Van Buren PN, Lewis JB, Dwyer JP, Greene T, Middleton J, Sika M, Umanath K, Abraham JD, Arfeen SS, Bowline IG, Chernin G, Fadem SZ, Goral S, Koury M, Sinsakul MV, Weiner DE, Collaborative Study G (2015) 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 66:479–488

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Cozzolino M, Funk F, Rakov V, Phan O, Teitelbaum I (2014) Preclinical pharmacokinetics, pharmacodynamics and safety of sucroferric oxyhydroxide. Curr Drug Metab 15:953–965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Chong E, Kalia V, Willsie S, Winkle P (2014) Drug-drug interactions between sucroferric oxyhydroxide and losartan, furosemide, omeprazole, digoxin and warfarin in healthy subjects. J Nephrol 27(6):659–666

  101. Phan O, Maillard M, Funk F, Stehle JC, Burnier M (2015) 1d.08: effect of Pa21, a new iron-based phosphate binder on fibroblast growth factor 23 (Fgf23) and vascular calcifications in uremic rats. J Hypertens 33(Suppl 1):e16–e17

    Article  PubMed  Google Scholar 

  102. Wuthrich RP, Chonchol M, Covic A, Gaillard S, Chong E, Tumlin JA (2013) Randomized clinical trial of the iron-based phosphate binder PA21 in hemodialysis patients. Clin J Am Soc Nephrol 8:280–289

    Article  PubMed  CAS  Google Scholar 

  103. Floege J, Covic AC, Ketteler M, Rastogi A, Chong EM, Gaillard S, Lisk LJ, Sprague SM, Group PAS (2014) A phase III study of the efficacy and safety of a novel iron-based phosphate binder in dialysis patients. Kidney Int 86:638–647

    Article  CAS  Google Scholar 

  104. Floege J, Covic AC, Ketteler M, Mann JF, Rastogi A, Spinowitz B, Chong EM, Gaillard S, Lisk LJ, Sprague SM, Sucroferric Oxyhydroxide Study G (2015) Long-term effects of the iron-based phosphate binder, sucroferric oxyhydroxide, in dialysis patients. Nephrol Dial Transpl 30:1037–1046

    Article  Google Scholar 

  105. Mudge DW, Johnson DW, Hawley CM, Campbell SB, Isbel NM, van Eps CL, Petrie JJ (2011) Do aluminium-based phosphate binders continue to have a role in contemporary nephrology practice? BMC Nephrol 12:20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Block GA, Persky MS, Shamblin BM, Baltazar MF, Singh B, Sharma A, Pergola P, Smits G, Comelli MC (2013) Effect of salivary phosphate-binding chewing gum on serum phosphate in chronic kidney disease. Nephron Clin Pract 123:93–101

    Article  CAS  PubMed  Google Scholar 

  107. Savica V, Calo LA, Monardo P, Davis PA, Granata A, Santoro D, Savica R, Musolino R, Comelli MC, Bellinghieri G (2009) Salivary phosphate-binding chewing gum reduces hyperphosphatemia in dialysis patients. J Am Soc Nephrol 20:639–644

    Article  PubMed  PubMed Central  Google Scholar 

  108. Akizawa T, Tsuruta Y, Okada Y, Miyauchi Y, Suda A, Kasahara H, Sasaki N, Maeda Y, Suzuki T, Matsui N, Niwayama J, Suzuki T, Hara H, Asano Y, Komemushi S, Fukagawa M (2014) Effect of chitosan chewing gum on reducing serum phosphorus in hemodialysis patients: a multi-center, randomized, double-blind, placebo-controlled trial. BMC Nephrol 15:98

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Oh MS, Uribarri J (2014) What can we learn from the saga of chitosan gums in hyperphosphatemia therapy? Clin J Am Soc Nephrol 9:967–970

    Article  PubMed  PubMed Central  Google Scholar 

  110. Nakaki J, Yamaguchi S, Torii Y, Inoue A, Minakami S, Kanno T, Murakami M, Tsuzuki M, Mochizuki H, Suyama K, Miyamoto M (2013) Effect of fatty acids on the phosphate binding of TRK-390, a novel, highly selective phosphate-binding polymer. Eur J Pharmacol 714:312–317

    Article  CAS  PubMed  Google Scholar 

  111. Moustafa M, Lehrner L, Al-Saghir F, Smith M, Goyal S, Dillon M, Hunter J, Holmes-Farley R (2014) A randomized, double-blind, placebo-controlled, dose-ranging study using Genz-644470 and sevelamer carbonate in hyperphosphatemic chronic kidney disease patients on hemodialysis. Int J Nephrol Renovasc Dis 7:141–152

    PubMed  PubMed Central  Google Scholar 

  112. Block GA, Brillhart SL, Persky MS, Amer A, Slade AJ (2010) Efficacy and safety of SBR759, a new iron-based phosphate binder. Kidney Int 77:897–903

    Article  CAS  PubMed  Google Scholar 

  113. Chen JB, Chiang SS, Chen HC, Obayashi S, Nagasawa M, Hexham JM, Balfour A, Junge G, Akiba T, Fukagawa M (2011) Efficacy and safety of SBR759, a novel calcium-free, iron(III)-based phosphate binder, in Asian patients undergoing hemodialysis: a 12-week, randomized, open-label, dose-titration study versus sevelamer hydrochloride. Nephrology (Carlton) 16:743–750

    Article  CAS  Google Scholar 

  114. Gschwind HP, Schmid DG, von Blanckenburg F, Oelze M, van Zuilen K, Slade AJ, Stitah S, Kaufmann D, Swart P (2014) Iron uptake and ferrokinetics in healthy male subjects of an iron-based oral phosphate binder (SBR759) labeled with the stable isotope (58)Fe. Metallomics 6:2062–2071

    Article  CAS  PubMed  Google Scholar 

  115. Tamagawa K, Nakayama-Imaohji H, Wakimoto S, Ichimura M, Kuwahara T (2010) Utilization of titanium oxide-like compound as an inorganic phosphate adsorbent for the control of serum phosphate level in chronic renal failure. J Med Invest 57:275–283

    Article  PubMed  Google Scholar 

  116. Schiavi SC, Tang W, Bracken C, O’Brien SP, Song W, Boulanger J, Ryan S, Phillips L, Liu S, Arbeeny C, Ledbetter S, Sabbagh Y (2012) Npt2b deletion attenuates hyperphosphatemia associated with CKD. J Am Soc Nephrol 23:1691–1700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Maccubbin D, Tipping D, Kuznetsova O, Hanlon WA, Bostom AG (2010) Hypophosphatemic effect of niacin in patients without renal failure: a randomized trial. Clin J Am Soc Nephrol 5:582–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Cheng SC, Young DO, Huang Y, Delmez JA, Coyne DW (2008) A randomized, double-blind, placebo-controlled trial of niacinamide for reduction of phosphorus in hemodialysis patients. Clin J Am Soc Nephrol 3:1131–1138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. El Borolossy R, El Wakeel LM, El Hakim I, Sabri N (2016) Efficacy and safety of nicotinamide in the management of hyperphosphatemia in pediatric patients on regular hemodialysis. Pediatr Nephrol 31(2):289–296

  120. Pelletier S, Roth H, Bouchet JL, Drueke T, London G, Fouque D, French P, Calcium Observatory i (2010) Mineral and bone disease pattern in elderly haemodialysis patients. Nephrol Dial Transpl 25:3062–3070

    Article  CAS  Google Scholar 

  121. Tamura MK, Tan JC, O’Hare AM (2012) Optimizing renal replacement therapy in older adults: a framework for making individualized decisions. Kidney Int 82:261–269

    Article  PubMed  Google Scholar 

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  1. Department of Nephrology and Clinical Immunology, University Hospital, RWTH University of Aachen, Pauwelsstr. 30, 52057, Aachen, Germany

    Jürgen Floege

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The author has received speaker honoraria and/or consultancy honoraria from Amgen, Chugai, Fresenius, Sanofi, Shire and Vifor.

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Floege, J. Phosphate binders in chronic kidney disease: a systematic review of recent data. J Nephrol 29, 329–340 (2016). https://doi.org/10.1007/s40620-016-0266-9

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