Review ArticleReview Article
Open Access

Hyperphosphatemia

The hidden killer in chronic kidney disease

Akram M. Askar
Saudi Medical Journal January 2015, 36 (1) 13-19; DOI: https://doi.org/10.15537/smj.2015.1.9843

References

  1. ↵
    1. Gilbert S,
    2. Weiner D,
    3. Gipson DS,
    4. Perazella MA,
    5. Tonelli M
    (2014) National Kidney Foundation's Primer on Kidney Diseases (Elsevier, Boston (MA)), 6th ed.
  2. ↵
    1. Kuro-o M
    (2012) Klotho in health and disease. Curr Opin Nephrol Hypertens 21:362–368.
    OpenUrlCrossRefPubMed
  3. ↵
    1. Dhingra R,
    2. Sullivan LM,
    3. Fox CS,
    4. Wang TJ,
    5. D’Agostino RB Sr.,
    6. Gaziano JM,
    7. et al.
    (2007) Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med 167:879–885.
    OpenUrlCrossRefPubMedWeb of Science
  4. ↵
    1. Foley RN,
    2. Collins AJ,
    3. Herzog CA,
    4. Ishani A,
    5. Kalra PA
    (2009) Serum phosphorus levels associate with coronary atherosclerosis in young adults. J Am Soc Nephrol 20:397–404.
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Kestenbaum B,
    2. Sampson JN,
    3. Rudser KD,
    4. Patterson DJ,
    5. Seliger SL,
    6. Young B,
    7. et al.
    (2005) Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 16:520–528.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Block GA,
    2. Klassen PS,
    3. Lazarus JM,
    4. Ofsthun N,
    5. Lowrie EG,
    6. Chertow GM
    (2004) Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 15:2208–2218.
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Calò LA,
    2. Savica V,
    3. Piccoli A,
    4. Fusaro M,
    5. D’Angelo A,
    6. Davis PA
    (2011) Reduction of hyperphosphatemia is related with the reduction of C-reactive protein in dialysis patients. Study in sevelamer-resistant dialysis patients treated with chitosan chewing gum as salivary phosphate binder. Ren Fail 33:11–14.
    OpenUrlCrossRefPubMed
  8. ↵
    1. Giachelli CM
    (2004) Vascular calcification mechanisms. J Am Soc Nephrol 15:2959–2964.
    OpenUrlAbstract/FREE Full Text
  9. (2013) National Institute of Diseases and Digestive and Kidney Disease. US Renal Data System 2012 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Am J Kidney Dis 61:1–480.
    OpenUrl
  10. ↵
    1. Shamseddin MK,
    2. Parfrey PS
    (2011) Sudden cardiac death in chronic kidney disease: epidemiology and prevention. Nat Rev Nephrol 7:145–154.
    OpenUrlCrossRefPubMedWeb of Science
  11. ↵
    1. Garimella PS,
    2. Hart PD,
    3. O’Hare A,
    4. DeLoach S,
    5. Herzog CA,
    6. Hirsch AT
    (2012) Peripheral artery disease and CKD: a focus on peripheral artery disease as a critical component of CKD care. Am J Kidney Dis 60:641–654.
    OpenUrlCrossRefPubMed
  12. ↵
    1. Yang H,
    2. Curinga G,
    3. Giachelli CM
    (2004) Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro. Kidney Int 66:2293–2299.
    OpenUrlCrossRefPubMedWeb of Science
  13. ↵
    1. Glassock RJ,
    2. Pecoits-Filho R,
    3. Barberato SH
    (2009) Left ventricular mass in chronic kidney disease and ESRD. Clin J Am Soc Nephrol 4(Suppl 1):S79–S91.
    OpenUrlAbstract/FREE Full Text
  14. ↵
    1. Nakamura S,
    2. Ishibashi-Ueda H,
    3. Niizuma S,
    4. Yoshihara F,
    5. Horio T,
    6. Kawano Y
    (2009) Coronary calcification in patients with chronic kidney disease and coronary artery disease. Clin J Am Soc Nephrol 4:1892–1900.
    OpenUrlAbstract/FREE Full Text
  15. ↵
    1. Jono S,
    2. McKee MD,
    3. Murry CE,
    4. Shioi A,
    5. Nishizawa Y,
    6. Mori K,
    7. et al.
    (2000) Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 87:10–17.
    OpenUrlCrossRef
  16. ↵
    1. Shanahan CM
    (2005) Vascular calcification. Curr Opin Nephrol Hypertens 14:361–367.
    OpenUrlPubMedWeb of Science
  17. ↵
    1. El-Abbadi M,
    2. Giachelli CM
    (2005) Arteriosclerosis, calcium phosphate deposition and cardiovascular disease in uremia: current concepts at the bench. Curr Opin Nephrol Hypertens 14:519–524.
    OpenUrlPubMedWeb of Science
  18. ↵
    1. Shanahan CM,
    2. Crouthamel MH,
    3. Kapustin A,
    4. Giachelli CM
    (2011) Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res 109:697–711.
    OpenUrlAbstract/FREE Full Text
  19. ↵
    1. Chen NX,
    2. Moe SM
    (2012) Vascular calcification: pathophysiology and risk factors. Curr Hypertens Rep 14:228–237.
    OpenUrlCrossRefPubMed
  20. ↵
    1. Karohl C,
    2. Raggi P
    (2013) Medscape Education Nephrology, Current Insights in Chronic Kidney Disease-Mineral and Bone Disorder. available from: http://www.medscape.org/viewarticle/779579.
  21. ↵
    1. Hermans MM,
    2. Brandenburg V,
    3. Ketteler M,
    4. Kooman JP,
    5. van der Sande FM,
    6. Boeschoten EW,
    7. et al.
    (2007) Association of serum fetuin-A levels with mortality in dialysis patients. Kidney Int 72:202–207.
    OpenUrlCrossRefPubMedWeb of Science
  22. ↵
    1. Wang AY,
    2. Woo J,
    3. Lam CW,
    4. Wang M,
    5. Chan IH,
    6. Gao P,
    7. et al.
    (2005) Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transplant 20:1676–1685.
    OpenUrlCrossRefPubMedWeb of Science
    1. Stenvinkel P,
    2. Wang K,
    3. Qureshi AR,
    4. Axelsson J,
    5. Pecoits-Filho R,
    6. Gao P,
    7. et al.
    (2005) Low fetuin-A levels are associated with cardiovascular death: Impact of variations in the gene encoding fetuin. Kidney Int 67:2383–2392.
    OpenUrlCrossRefPubMedWeb of Science
    1. Honda H,
    2. Qureshi AR,
    3. Heimbürger O,
    4. Barany P,
    5. Wang K,
    6. Pecoits-Filho R,
    7. et al.
    (2006) Serum albumin, C-reactive protein, interleukin 6, and fetuin a as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD. Am J Kidney Dis 47:139–148.
    OpenUrlCrossRefPubMedWeb of Science
  25. ↵
    1. Hermans MM,
    2. Brandenburg V,
    3. Ketteler M,
    4. Kooman JP,
    5. van der Sande FM,
    6. Gladziwa U,
    7. et al.
    (2006) Study on the relationship of serum fetuin-A concentration with aortic stiffness in patients on dialysis. Nephrol Dial Transplant 21:1293–1299.
    OpenUrlCrossRefPubMedWeb of Science
  26. ↵
    1. Adeney KL,
    2. Siscovick DS,
    3. Ix JH,
    4. Seliger SL,
    5. Shlipak MG,
    6. Jenny NS,
    7. et al.
    (2009) Association of serum phosphate with vascular and valvular calcification in moderate CKD. J Am Soc Nephrol 20:381–387.
    OpenUrlFREE Full Text
  27. ↵
    1. Giachelli CM
    (2009) The emerging role of phosphate in vascular calcification. Kidney Int 75:890–897.
    OpenUrlCrossRefPubMedWeb of Science
  28. ↵
    1. Zhao MM,
    2. Xu MJ,
    3. Cai Y,
    4. Zhao G,
    5. Guan Y,
    6. Kong W,
    7. et al.
    (2011) Mitochondrial reactive oxygen species promote p65 nuclear translocation mediating high-phosphate-induced vascular calcification in vitro and in vivo. Kidney Int 79:1071–1079.
    OpenUrlCrossRefPubMedWeb of Science
  29. ↵
    1. Al-Aly Z
    (2011) Phosphate, oxidative stress, and nuclear factor-κB activation in vascular calcification. Kidney Int 79:1044–1047.
    OpenUrlCrossRefPubMedWeb of Science
  30. ↵
    1. Bushinsky DA
    (2010) Contribution of intestine, bone, kidney, and dialysis to extracellular fluid calcium content. Clin J Am Soc Nephrol 5(Suppl 1):S12–S22.
    OpenUrlAbstract/FREE Full Text
  31. ↵
    1. Karohl C,
    2. de Paiva Paschoal J,
    3. de Castro MC,
    4. Elias RM,
    5. Abensur H,
    6. Romão JE Jr.,
    7. et al.
    (2010) Effects of bone remodelling on calcium mass transfer during haemodialysis. Nephrol Dial Transplant 25:1244–1251.
    OpenUrlCrossRefPubMedWeb of Science
  32. ↵
    1. Block GA,
    2. Spiegel DM,
    3. Ehrlich J,
    4. Mehta R,
    5. Lindbergh J,
    6. Dreisbach A,
    7. et al.
    (2005) Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int 68:1815–1824.
    OpenUrlCrossRefPubMedWeb of Science
  33. ↵
    1. Block GA,
    2. Klassen PS,
    3. Lazarus JM,
    4. Ofsthun N,
    5. Lowrie EG,
    6. Chertow GM
    (2004) Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 15:2208–2218.
    OpenUrlAbstract/FREE Full Text
  34. ↵
    1. Young EW,
    2. Albert JM,
    3. Satayathum S,
    4. Goodkin DA,
    5. Pisoni RL,
    6. Akiba T,
    7. et al.
    (2005) Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study. Kidney Int 67:1179–1187.
    OpenUrlCrossRefPubMedWeb of Science
  35. ↵
    1. Neves KR,
    2. Graciolli FG,
    3. dos Reis LM,
    4. Graciolli RG,
    5. Neves CL,
    6. Magalhães AO,
    7. et al.
    (2007) Vascular calcification: contribution of parathyroid hormone in renal failure. Kidney Int 71:1262–1270.
    OpenUrlCrossRefPubMedWeb of Science
  36. ↵
    1. Katsumata K,
    2. Kusano K,
    3. Hirata M,
    4. Tsunemi K,
    5. Nagano N,
    6. Burke SK,
    7. et al.
    (2003) Sevelamer hydrochloride prevents ectopic calcification and renal osteodystrophy in chronic renal failure rats. Kidney Int 64:441–450.
    OpenUrlCrossRefPubMedWeb of Science
  37. ↵
    1. Benini O,
    2. D’Alessandro C,
    3. Gianfaldoni D,
    4. Cupisti A
    (2011) Extra-phosphate load from food additives in commonly eaten foods: a real and insidious danger for renal patients. J Ren Nutr 21:303–308.
    OpenUrlCrossRefPubMed
  38. ↵
    1. Savica V,
    2. Calò LA,
    3. Monardo P,
    4. Santoro D,
    5. Mallamace A,
    6. Muraca U,
    7. et al.
    (2009) Salivary phosphorus and phosphate content of beverages: implications for the treatment of uremic hyperphosphatemia. J Ren Nutr 19:69–72.
    OpenUrlPubMed
  39. ↵
    1. Bellinghieri G,
    2. Santoro D,
    3. Savica V
    (2007) Emerging drugs for hyperphosphatemia. Expert Opin Emerg Drugs 12:355–365.
    OpenUrlCrossRefPubMedWeb of Science
  40. ↵
    1. Savica V,
    2. Bellinghieri G,
    3. Monardo P,
    4. Muraca U,
    5. Santoro D
    (2013) An update on calcium metabolism alterations and cardiovascular risk in patients with chronic kidney disease: questions, myths and facts. J Nephrol 26:456–464.
    OpenUrl
  41. ↵
    1. Block GA,
    2. Raggi P,
    3. Bellasi A,
    4. Kooienga L,
    5. Spiegel DM
    (2007) Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int 71:438–441.
    OpenUrlCrossRefPubMedWeb of Science
  42. ↵
    1. Suki WN,
    2. Dialysis Clinical Outcomes Revisited Investigators
    (2008) Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients: results of a randomized clinical trial. J Ren Nutr 18:91–98.
    OpenUrlCrossRefPubMedWeb of Science
  43. ↵
    1. Savica V,
    2. Monardo P,
    3. Santoro D,
    4. Mallamace A,
    5. Bellinghieri G
    (2008) Time-dependent effect of sevelamerHCl on the cardiovascular system. Nephrol Dial Transplant 23:2102–2103.
    OpenUrlCrossRefPubMedWeb of Science
  44. ↵
    1. Hutchison AJ,
    2. Speake M,
    3. Al-Baaj F
    (2004) 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 19:1902–1906.
    OpenUrlCrossRefPubMedWeb of Science
  45. ↵
    1. Hutchison AJ,
    2. Laville M,
    3. SPD405-313 Lanthanum Study Group
    (2008) Switching to lanthanum carbonate monotherapy provides effective phosphate control with a low tablet burden. Nephrol Dial Transplant 23:3677–3684.
    OpenUrlCrossRefPubMedWeb of Science
  46. ↵
    1. Takahashi Y,
    2. Tanaka A,
    3. Nakamura T,
    4. Fukuwatari T,
    5. Shibata K,
    6. Shimada N,
    7. et al.
    (2004) Nicotinamide suppresses hyperphosphatemia in hemodialysis patients. Kidney Int 65:1099–1104.
    OpenUrlCrossRefPubMedWeb of Science
  47. ↵
    1. Savica V,
    2. Calò L,
    3. Santoro D,
    4. Monardo P,
    5. Granata A,
    6. Bellinghieri G
    (2008) Salivary phosphate secretion in chronic kidney disease. J Ren Nutr 18:87–90.
    OpenUrlCrossRefPubMed
  48. ↵
    1. Savica V,
    2. Calò LA,
    3. Caldarera R,
    4. Cavaleri A,
    5. Granata A,
    6. Santoro D,
    7. et al.
    (2007) Phosphate salivary secretion in hemodialysis patients: implications for the treatment of hyperphosphatemia. Nephron Physiol 105:52–55.
    OpenUrlCrossRefPubMed
  49. ↵
    1. Savica V,
    2. Calò LA,
    3. Monardo P,
    4. Davis PA,
    5. Granata A,
    6. Santoro D,
    7. et al.
    (2009) Salivary phosphate-binding chewing gum reduces hyperphosphatemia in dialysis patients. J Am Soc Nephrol 20:639–644.
    OpenUrlAbstract/FREE Full Text
  50. ↵
    1. Savica V,
    2. Calò LA,
    3. Santoro D,
    4. Monardo P,
    5. Santoro G,
    6. Muraca U,
    7. et al.
    (2011) Salivary glands: a new player in phosphorus metabolism. J Ren Nutr 21:39–42.
    OpenUrlPubMed
  51. ↵
    1. Iida A,
    2. Kemmochi Y,
    3. Kakimoto K,
    4. Tanimoto M,
    5. Mimura T,
    6. Shinozaki Y,
    7. et al.
    (2013) Ferric citrate hydrate, a new phosphate binder, prevents the complications of secondary hyperparathyroidism and vascular calcification. Am J Nephrol 37:346–358.
    OpenUrlCrossRefPubMed
  52. ↵
    1. Dwyer JP,
    2. Sika M,
    3. Schulman G,
    4. Chang IJ,
    5. Anger M,
    6. Smith M,
    7. et al.
    (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.
    OpenUrlCrossRefPubMedWeb of Science
  53. ↵
    1. Wüthrich RP,
    2. Chonchol M,
    3. Covic A,
    4. Gaillard S,
    5. Chong E,
    6. Tumlin JA
    (2013) Randomized clinical trial of the iron-based phosphate binder PA21 in hemodialysis patients. Clin J Am Soc Nephrol 8:280–289.
    OpenUrlAbstract/FREE Full Text
Back to top

In this issue

Print
Download PDF
Email Article
Citation Tools
Bookmark this article

Jump to section