UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Causes of hypophosphatemia

Authors
Alan S L Yu, MB, BChir
Jason R Stubbs, MD
Section Editor
Stanley Goldfarb, MD
Deputy Editor
Albert Q Lam, MD

INTRODUCTION

The reported prevalence of hypophosphatemia varies widely, depending upon the patient population surveyed and the concentration of serum phosphorus used to define hypophosphatemia. Up to 5 percent of hospitalized patients may have low serum phosphate concentrations (less than 2.5 mg/dL [0.80 mmol/L]), although prevalences of over 30 to 50 percent have been reported in alcoholic patients and patients with severe sepsis or trauma [1-3]. Profound hypophosphatemia (less than 1 mg/dL [0.32 mmol/L]), which can lead to physiological disturbances and symptoms, is much less common [3-5]. (See "Signs and symptoms of hypophosphatemia".)

There are four major mechanisms by which hypophosphatemia can occur (table 1):

Redistribution of phosphate from the extracellular fluid into cells

Decreased intestinal absorption of phosphate

Increased urinary phosphate excretion

                 

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Wed Apr 13 00:00:00 GMT 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Larsson L, Rebel K, Sörbo B. Severe hypophosphatemia--a hospital survey. Acta Med Scand 1983; 214:221.
  2. King AL, Sica DA, Miller G, Pierpaoli S. Severe hypophosphatemia in a general hospital population. South Med J 1987; 80:831.
  3. Gaasbeek A, Meinders AE. Hypophosphatemia: an update on its etiology and treatment. Am J Med 2005; 118:1094.
  4. Halevy J, Bulvik S. Severe hypophosphatemia in hospitalized patients. Arch Intern Med 1988; 148:153.
  5. Subramanian R, Khardori R. Severe hypophosphatemia. Pathophysiologic implications, clinical presentations, and treatment. Medicine (Baltimore) 2000; 79:1.
  6. Paterson CR. Hypophosphataemia: a dangerous disorder. Nutrition 1996; 12:540.
  7. Marinella MA. Refeeding syndrome and hypophosphatemia. J Intensive Care Med 2005; 20:155.
  8. Brautbar N, Leibovici H, Massry SG. On the mechanism of hypophosphatemia during acute hyperventilation: evidence for increased muscle glycolysis. Miner Electrolyte Metab 1983; 9:45.
  9. MOSTELLAR ME, TUTTLE EP Jr. EFFECTS OF ALKALOSIS ON PLASMA CONCENTRATION AND URINARY EXCRETION OF INORGANIC PHOSPHATE IN MAN. J Clin Invest 1964; 43:138.
  10. Laaban JP, Waked M, Laromiguiere M, et al. Hypophosphatemia complicating management of acute severe asthma. Ann Intern Med 1990; 112:68.
  11. Paleologos M, Stone E, Braude S. Persistent, progressive hypophosphataemia after voluntary hyperventilation. Clin Sci (Lond) 2000; 98:619.
  12. Nowack R, Wachtler P. Hypophosphatemia and hungry bone syndrome in a dialysis patient with secondary hyperparathyroidism treated with cinacalcet--proposal for an improved monitoring. Clin Lab 2006; 52:583.
  13. Murer H. Homer Smith Award. Cellular mechanisms in proximal tubular Pi reabsorption: some answers and more questions. J Am Soc Nephrol 1992; 2:1649.
  14. Murer H, Lötscher M, Kaissling B, et al. Renal brush border membrane Na/Pi-cotransport: molecular aspects in PTH-dependent and dietary regulation. Kidney Int 1996; 49:1769.
  15. Lotz M, Zisman E, Bartter FC. Evidence for a phosphorus-depletion syndrome in man. N Engl J Med 1968; 278:409.
  16. Buell JF, Berger AC, Plotkin JS, et al. The clinical implications of hypophosphatemia following major hepatic resection or cryosurgery. Arch Surg 1998; 133:757.
  17. Maccubbin D, Tipping D, Kuznetsova O, et al. Hypophosphatemic effect of niacin in patients without renal failure: a randomized trial. Clin J Am Soc Nephrol 2010; 5:582.
  18. Ix JH, Ganjoo P, Tipping D, et al. Sustained hypophosphatemic effect of once-daily niacin/laropiprant in dyslipidemic CKD stage 3 patients. Am J Kidney Dis 2011; 57:963.
  19. Antoniucci DM, Yamashita T, Portale AA. Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men. J Clin Endocrinol Metab 2006; 91:3144.
  20. Miyamoto K, Ito M, Tatsumi S, et al. New aspect of renal phosphate reabsorption: the type IIc sodium-dependent phosphate transporter. Am J Nephrol 2007; 27:503.
  21. Nafidi O, Lapointe RW, Lepage R, et al. Mechanisms of renal phosphate loss in liver resection-associated hypophosphatemia. Ann Surg 2009; 249:824.
  22. Gattineni J, Baum M. Regulation of phosphate transport by fibroblast growth factor 23 (FGF23): implications for disorders of phosphate metabolism. Pediatr Nephrol 2010; 25:591.
  23. Habra MA, Jimenez C, Huang SC, et al. Expression analysis of fibroblast growth factor-23, matrix extracellular phosphoglycoprotein, secreted frizzled-related protein-4, and fibroblast growth factor-7: identification of fibroblast growth factor-23 and matrix extracellular phosphoglycoprotein as major factors involved in tumor-induced osteomalacia. Endocr Pract 2008; 14:1108.
  24. Berndt T, Thomas LF, Craig TA, et al. Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorption. Proc Natl Acad Sci U S A 2007; 104:11085.
  25. Kawata T, Imanishi Y, Kobayashi K, et al. Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism. J Am Soc Nephrol 2007; 18:2683.
  26. Tenenhouse HS, Murer H. Disorders of renal tubular phosphate transport. J Am Soc Nephrol 2003; 14:240.
  27. A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets. The HYP Consortium. Nat Genet 1995; 11:130.
  28. White KE, Carn G, Lorenz-Depiereux B, et al. Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23. Kidney Int 2001; 60:2079.
  29. Hasani-Ranjbar S, Amoli MM, Ebrahim-Habibi A, et al. SLC34A3 intronic deletion in a new kindred with hereditary hypophosphatemic rickets with hypercalciuria. J Clin Res Pediatr Endocrinol 2012; 4:89.
  30. Prié D, Huart V, Bakouh N, et al. Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med 2002; 347:983.
  31. Lapointe JY, Tessier J, Paquette Y, et al. NPT2a gene variation in calcium nephrolithiasis with renal phosphate leak. Kidney Int 2006; 69:2261.
  32. Karim Z, Gérard B, Bakouh N, et al. NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med 2008; 359:1128.
  33. Lorenz-Depiereux B, Bastepe M, Benet-Pagès A, et al. DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis. Nat Genet 2006; 38:1248.
  34. Liu S, Zhou J, Tang W, et al. Pathogenic role of Fgf23 in Dmp1-null mice. Am J Physiol Endocrinol Metab 2008; 295:E254.
  35. Saito T, Shimizu Y, Hori M, et al. A patient with hypophosphatemic rickets and ossification of posterior longitudinal ligament caused by a novel homozygous mutation in ENPP1 gene. Bone 2011; 49:913.
  36. Brownstein CA, Adler F, Nelson-Williams C, et al. A translocation causing increased alpha-klotho level results in hypophosphatemic rickets and hyperparathyroidism. Proc Natl Acad Sci U S A 2008; 105:3455.
  37. Wilkins GE, Granleese S, Hegele RG, et al. Oncogenic osteomalacia: evidence for a humoral phosphaturic factor. J Clin Endocrinol Metab 1995; 80:1628.
  38. Riminucci M, Collins MT, Fedarko NS, et al. FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. J Clin Invest 2003; 112:683.
  39. Bhan I, Shah A, Holmes J, et al. Post-transplant hypophosphatemia: Tertiary 'Hyper-Phosphatoninism'? Kidney Int 2006; 70:1486.
  40. Pande S, Ritter CS, Rothstein M, et al. FGF-23 and sFRP-4 in chronic kidney disease and post-renal transplantation. Nephron Physiol 2006; 104:p23.
  41. Ghanekar H, Welch BJ, Moe OW, Sakhaee K. Post-renal transplantation hypophosphatemia: a review and novel insights. Curr Opin Nephrol Hypertens 2006; 15:97.
  42. Evenepoel P, Naesens M, Claes K, et al. Tertiary 'hyperphosphatoninism' accentuates hypophosphatemia and suppresses calcitriol levels in renal transplant recipients. Am J Transplant 2007; 7:1193.
  43. Evenepoel P, Meijers BK, de Jonge H, et al. Recovery of hyperphosphatoninism and renal phosphorus wasting one year after successful renal transplantation. Clin J Am Soc Nephrol 2008; 3:1829.
  44. Lee HW, Suh KS, Kim J, et al. Hypophosphatemia after live donor right hepatectomy. Surgery 2008; 144:448.
  45. Salem RR, Tray K. Hepatic resection-related hypophosphatemia is of renal origin as manifested by isolated hyperphosphaturia. Ann Surg 2005; 241:343.
  46. Clarke BL, Wynne AG, Wilson DM, Fitzpatrick LA. Osteomalacia associated with adult Fanconi's syndrome: clinical and diagnostic features. Clin Endocrinol (Oxf) 1995; 43:479.
  47. Okada M, Imamura K, Iida M, et al. Hypophosphatemia induced by intravenous administration of Saccharated iron oxide. Klin Wochenschr 1983; 61:99.
  48. Fernández-Fernández FJ, Martín-Fernández A. Parenteral iron as a cause of hypophosphataemia. BMJ 2014; 349:g4616.
  49. Schouten BJ, Hunt PJ, Livesey JH, et al. FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study. J Clin Endocrinol Metab 2009; 94:2332.
  50. Wolf M, Koch TA, Bregman DB. Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res 2013; 28:1793.
  51. Berman E, Nicolaides M, Maki RG, et al. Altered bone and mineral metabolism in patients receiving imatinib mesylate. N Engl J Med 2006; 354:2006.
  52. Owen S, Hatfield A, Letvak L. Imatinib and altered bone and mineral metabolism. N Engl J Med 2006; 355:627; author reply 628.
  53. Kempe DS, Dërmaku-Sopjani M, Fröhlich H, et al. Rapamycin-induced phosphaturia. Nephrol Dial Transplant 2010; 25:2938.
  54. Hutson TE, Figlin RA, Kuhn JG, Motzer RJ. Targeted therapies for metastatic renal cell carcinoma: an overview of toxicity and dosing strategies. Oncologist 2008; 13:1084.
  55. Bellini E, Pia A, Brizzi MP, et al. Sorafenib may induce hypophosphatemia through a fibroblast growth factor-23 (FGF23)-independent mechanism. Ann Oncol 2011; 22:988.
  56. Broman M, Carlsson O, Friberg H, et al. Phosphate-containing dialysis solution prevents hypophosphatemia during continuous renal replacement therapy. Acta Anaesthesiol Scand 2011; 55:39.