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

Causes of hypomagnesemia

Alan S L Yu, MB, BChir
Section Editor
Stanley Goldfarb, MD
Deputy Editor
John P Forman, MD, MSc


Hypomagnesemia is a common entity occurring in up to 12 percent of hospitalized patients [1]. The incidence rises to as high as 60 to 65 percent in patients in an intensive care setting in which nutrition, diuretics, hypoalbuminemia, and aminoglycosides may play important roles [2-5]. The kidney can, in the presence of magnesium depletion, lower magnesium excretion to very low levels; the stimulus for this response is a fall in the plasma magnesium concentration. (See "Regulation of magnesium balance".)

There are two major mechanisms by which hypomagnesemia can be induced: gastrointestinal or renal losses (table 1). Regardless of the cause, hypomagnesemia begins to occur after a relatively small magnesium deficit because there is little rapid exchange of extracellular magnesium with the much larger bone and cell stores.

Hypomagnesemia is often associated with hypokalemia (due to urinary potassium wasting) and hypocalcemia (due both to lower parathyroid hormone secretion and end-organ resistance to its effect). (See "Clinical manifestations of magnesium depletion".)

The major causes of hypomagnesemia will be reviewed in this topic. The regulation of magnesium balance, the signs and symptoms of hypomagnesemia, and the evaluation and treatment of patients with hypomagnesemia are presented elsewhere. (See "Regulation of magnesium balance" and "Clinical manifestations of magnesium depletion" and "Evaluation and treatment of hypomagnesemia".)


Gastrointestinal secretions contain some magnesium, and potential losses are continuous and not regulated. Although the obligatory losses are not large, marked dietary deprivation can lead to progressive magnesium depletion.


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: Jan 2016. | This topic last updated: Feb 4, 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.
  1. Wong ET, Rude RK, Singer FR, Shaw ST Jr. A high prevalence of hypomagnesemia and hypermagnesemia in hospitalized patients. Am J Clin Pathol 1983; 79:348.
  2. Chernow B, Bamberger S, Stoiko M, et al. Hypomagnesemia in patients in postoperative intensive care. Chest 1989; 95:391.
  3. Desai TK, Carlson RW, Geheb MA. Prevalence and clinical implications of hypocalcemia in acutely ill patients in a medical intensive care setting. Am J Med 1988; 84:209.
  4. Ryzen E. Magnesium homeostasis in critically ill patients. Magnesium 1989; 8:201.
  5. Tong GM, Rude RK. Magnesium deficiency in critical illness. J Intensive Care Med 2005; 20:3.
  6. Paunier L, Radde IC, Kooh SW, et al. Primary hypomagnesemia with secondary hypocalcemia in an infant. Pediatrics 1968; 41:385.
  7. Walder RY, Shalev H, Brennan TM, et al. Familial hypomagnesemia maps to chromosome 9q, not to the X chromosome: genetic linkage mapping and analysis of a balanced translocation breakpoint. Hum Mol Genet 1997; 6:1491.
  8. Schlingmann KP, Weber S, Peters M, et al. Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nat Genet 2002; 31:166.
  9. Walder RY, Landau D, Meyer P, et al. Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia. Nat Genet 2002; 31:171.
  10. Huang CL. The transient receptor potential superfamily of ion channels. J Am Soc Nephrol 2004; 15:1690.
  11. Schlingmann KP, Sassen MC, Weber S, et al. Novel TRPM6 mutations in 21 families with primary hypomagnesemia and secondary hypocalcemia. J Am Soc Nephrol 2005; 16:3061.
  12. Guran T, Akcay T, Bereket A, et al. Clinical and molecular characterization of Turkish patients with familial hypomagnesaemia: novel mutations in TRPM6 and CLDN16 genes. Nephrol Dial Transplant 2012; 27:667.
  13. Voets T, Nilius B, Hoefs S, et al. TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption. J Biol Chem 2004; 279:19.
  14. Ryzen E, Rude RK. Low intracellular magnesium in patients with acute pancreatitis and hypocalcemia. West J Med 1990; 152:145.
  15. Hess MW, Hoenderop JG, Bindels RJ, Drenth JP. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther 2012; 36:405.
  16. Epstein M, McGrath S, Law F. Proton-pump inhibitors and hypomagnesemic hypoparathyroidism. N Engl J Med 2006; 355:1834.
  17. Broeren MA, Geerdink EA, Vader HL, van den Wall Bake AW. Hypomagnesemia induced by several proton-pump inhibitors. Ann Intern Med 2009; 151:755.
  18. Cundy T, Dissanayake A. Severe hypomagnesaemia in long-term users of proton-pump inhibitors. Clin Endocrinol (Oxf) 2008; 69:338.
  19. Danziger J, William JH, Scott DJ, et al. Proton-pump inhibitor use is associated with low serum magnesium concentrations. Kidney Int 2013; 83:692.
  20. Koulouridis I, Alfayez M, Tighiouart H, et al. Out-of-hospital use of proton pump inhibitors and hypomagnesemia at hospital admission: a nested case-control study. Am J Kidney Dis 2013; 62:730.
  21. Park CH, Kim EH, Roh YH, et al. The association between the use of proton pump inhibitors and the risk of hypomagnesemia: a systematic review and meta-analysis. PLoS One 2014; 9:e112558.
  22. Zipursky J, Macdonald EM, Hollands S, et al. Proton pump inhibitors and hospitalization with hypomagnesemia: a population-based case-control study. PLoS Med 2014; 11:e1001736.
  23. Perazella MA. Proton pump inhibitors and hypomagnesemia: a rare but serious complication. Kidney Int 2013; 83:553.
  24. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm245275.htm (Accessed on March 08, 2011).
  25. Shah GM, Kirschenbaum MA. Renal magnesium wasting associated with therapeutic agents. Miner Electrolyte Metab 1991; 17:58.
  26. Foster JE, Harpur ES, Garland HO. An investigation of the acute effect of gentamicin on the renal handling of electrolytes in the rat. J Pharmacol Exp Ther 1992; 261:38.
  27. Lajer H, Kristensen M, Hansen HH, et al. Magnesium and potassium homeostasis during cisplatin treatment. Cancer Chemother Pharmacol 2005; 55:231.
  28. Elisaf M, Merkouropoulos M, Tsianos EV, Siamopoulos KC. Pathogenetic mechanisms of hypomagnesemia in alcoholic patients. J Trace Elem Med Biol 1995; 9:210.
  29. De Marchi S, Cecchin E, Basile A, et al. Renal tubular dysfunction in chronic alcohol abuse--effects of abstinence. N Engl J Med 1993; 329:1927.
  30. Tosiello L. Hypomagnesemia and diabetes mellitus. A review of clinical implications. Arch Intern Med 1996; 156:1143.
  31. White JR Jr, Campbell RK. Magnesium and diabetes: a review. Ann Pharmacother 1993; 27:775.
  32. Ramos EL, Barri YM, Kubilis P, et al. Hypomagnesemia in renal transplant patients: improvement over time and association with hypertension and cyclosporine levels. Clin Transplant 1995; 9:185.
  33. Van Laecke S, Van Biesen W, Verbeke F, et al. Posttransplantation hypomagnesemia and its relation with immunosuppression as predictors of new-onset diabetes after transplantation. Am J Transplant 2009; 9:2140.
  34. Huang JW, Famure O, Li Y, Kim SJ. Hypomagnesemia and the Risk of New-Onset Diabetes Mellitus after Kidney Transplantation. J Am Soc Nephrol 2015.
  35. Nijenhuis T, Hoenderop JG, Bindels RJ. Downregulation of Ca(2+) and Mg(2+) transport proteins in the kidney explains tacrolimus (FK506)-induced hypercalciuria and hypomagnesemia. J Am Soc Nephrol 2004; 15:549.
  36. Gong Y, Hou J. Claudin-14 underlies Ca⁺⁺-sensing receptor-mediated Ca⁺⁺ metabolism via NFAT-microRNA-based mechanisms. J Am Soc Nephrol 2014; 25:745.
  37. Navaneethan SD, Sankarasubbaiyan S, Gross MD, et al. Tacrolimus-associated hypomagnesemia in renal transplant recipients. Transplant Proc 2006; 38:1320.
  38. Margreiter R, European Tacrolimus vs Ciclosporin Microemulsion Renal Transplantation Study Group. Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study. Lancet 2002; 359:741.
  39. Sánchez-Fructuoso AI, Santín Cantero JM, Pérez Flores I, et al. Changes in magnesium and potassium homeostasis after conversion from a calcineurin inhibitor regimen to an mTOR inhibitor-based regimen. Transplant Proc 2010; 42:3047.
  40. Wang WH, Lu M, Hebert SC. Cytochrome P-450 metabolites mediate extracellular Ca(2+)-induced inhibition of apical K+ channels in the TAL. Am J Physiol 1996; 271:C103.
  41. Wang W, Lu M, Balazy M, Hebert SC. Phospholipase A2 is involved in mediating the effect of extracellular Ca2+ on apical K+ channels in rat TAL. Am J Physiol 1997; 273:F421.
  42. Loupy A, Ramakrishnan SK, Wootla B, et al. PTH-independent regulation of blood calcium concentration by the calcium-sensing receptor. J Clin Invest 2012; 122:3355.
  43. Gong Y, Renigunta V, Himmerkus N, et al. Claudin-14 regulates renal Ca⁺⁺ transport in response to CaSR signalling via a novel microRNA pathway. EMBO J 2012; 31:1999.
  44. Dimke H, Desai P, Borovac J, et al. Activation of the Ca(2+)-sensing receptor increases renal claudin-14 expression and urinary Ca(2+) excretion. Am J Physiol Renal Physiol 2013; 304:F761.
  45. Evans RA, Carter JN, George CR, et al. The congenital "magnesium-losing kidney". Report of two patients. Q J Med 1981; 50:39.
  46. Geven WB, Monnens LA, Willems JL. Magnesium metabolism in childhood. Miner Electrolyte Metab 1993; 19:308.
  47. Freeman RM, Pearson E. Hypomagnesemia of unknown etiology. Am J Med 1966; 41:645.
  48. Runeberg L, Collan Y, Jokinen EJ, et al. Hypomagnesemia due to renal disease of unknown etiology. Am J Med 1975; 59:873.
  49. Booth BE, Johanson A. Hypomagnesemia due to renal tubular defect in reabsorption of magnesium. J Pediatr 1974; 85:350.
  50. Konrad M, Weber S. Recent advances in molecular genetics of hereditary magnesium-losing disorders. J Am Soc Nephrol 2003; 14:249.
  51. Kamel KS, Harvey E, Douek K, et al. Studies on the pathogenesis of hypokalemia in Gitelman's syndrome: role of bicarbonaturia and hypomagnesemia. Am J Nephrol 1998; 18:42.
  52. Schultheis PJ, Lorenz JN, Meneton P, et al. Phenotype resembling Gitelman's syndrome in mice lacking the apical Na+-Cl- cotransporter of the distal convoluted tubule. J Biol Chem 1998; 273:29150.
  53. Praga M, Vara J, González-Parra E, et al. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Kidney Int 1995; 47:1419.
  54. Nicholson JC, Jones CL, Powell HR, et al. Familial hypomagnesaemia--hypercalciuria leading to end-stage renal failure. Pediatr Nephrol 1995; 9:74.
  55. Benigno V, Canonica CS, Bettinelli A, et al. Hypomagnesaemia-hypercalciuria-nephrocalcinosis: a report of nine cases and a review. Nephrol Dial Transplant 2000; 15:605.
  56. Müller D, Kausalya PJ, Bockenhauer D, et al. Unusual clinical presentation and possible rescue of a novel claudin-16 mutation. J Clin Endocrinol Metab 2006; 91:3076.
  57. Konrad M, Hou J, Weber S, et al. CLDN16 genotype predicts renal decline in familial hypomagnesemia with hypercalciuria and nephrocalcinosis. J Am Soc Nephrol 2008; 19:171.
  58. Rodríguez-Soriano J, Vallo A. Pathophysiology of the renal acidification defect present in the syndrome of familial hypomagnesaemia-hypercalciuria. Pediatr Nephrol 1994; 8:431.
  59. Simon DB, Lu Y, Choate KA, et al. Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. Science 1999; 285:103.
  60. Blanchard A, Jeunemaitre X, Coudol P, et al. Paracellin-1 is critical for magnesium and calcium reabsorption in the human thick ascending limb of Henle. Kidney Int 2001; 59:2206.
  61. Weber S, Schneider L, Peters M, et al. Novel paracellin-1 mutations in 25 families with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. J Am Soc Nephrol 2001; 12:1872.
  62. Kausalya PJ, Amasheh S, Günzel D, et al. Disease-associated mutations affect intracellular traffic and paracellular Mg2+ transport function of Claudin-16. J Clin Invest 2006; 116:878.
  63. Godron A, Harambat J, Boccio V, et al. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: phenotype-genotype correlation and outcome in 32 patients with CLDN16 or CLDN19 mutations. Clin J Am Soc Nephrol 2012; 7:801.
  64. Hou J, Renigunta A, Konrad M, et al. Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex. J Clin Invest 2008; 118:619.
  65. Konrad M, Schaller A, Seelow D, et al. Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement. Am J Hum Genet 2006; 79:949.
  66. Meij IC, Saar K, van den Heuvel LP, et al. Hereditary isolated renal magnesium loss maps to chromosome 11q23. Am J Hum Genet 1999; 64:180.
  67. Meij IC, Koenderink JB, van Bokhoven H, et al. Dominant isolated renal magnesium loss is caused by misrouting of the Na(+),K(+)-ATPase gamma-subunit. Nat Genet 2000; 26:265.
  68. Meij IC, Koenderink JB, De Jong JC, et al. Dominant isolated renal magnesium loss is caused by misrouting of the Na+,K+-ATPase gamma-subunit. Ann N Y Acad Sci 2003; 986:437.
  69. Glaudemans B, van der Wijst J, Scola RH, et al. A missense mutation in the Kv1.1 voltage-gated potassium channel-encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia. J Clin Invest 2009; 119:936.
  70. Adalat S, Woolf AS, Johnstone KA, et al. HNF1B mutations associate with hypomagnesemia and renal magnesium wasting. J Am Soc Nephrol 2009; 20:1123.
  71. Wagner CA. Disorders of renal magnesium handling explain renal magnesium transport. J Nephrol 2007; 20:507.
  72. Groenestege WM, Thébault S, van der Wijst J, et al. Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia. J Clin Invest 2007; 117:2260.
  73. Ferrè S, de Baaij JH, Ferreira P, et al. Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting. J Am Soc Nephrol 2014; 25:574.
  74. Stuiver M, Lainez S, Will C, et al. CNNM2, encoding a basolateral protein required for renal Mg2+ handling, is mutated in dominant hypomagnesemia. Am J Hum Genet 2011; 88:333.
  75. Goytain A, Quamme GA. Functional characterization of ACDP2 (ancient conserved domain protein), a divalent metal transporter. Physiol Genomics 2005; 22:382.
  76. Aglio LS, Stanford GG, Maddi R, et al. Hypomagnesemia is common following cardiac surgery. J Cardiothorac Vasc Anesth 1991; 5:201.
  77. Palestine AG, Polis MA, De Smet MD, et al. A randomized, controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med 1991; 115:665.
  78. Scott VL, De Wolf AM, Kang Y, et al. Ionized hypomagnesemia in patients undergoing orthotopic liver transplantation: a complication of citrate intoxication. Liver Transpl Surg 1996; 2:343.
  79. Frisch LS, Mimouni F. Hypomagnesemia following correction of metabolic acidosis: a case of hungry bones. J Am Coll Nutr 1993; 12:710.
  80. Kang HC, Chung DE, Kim DW, Kim HD. Early- and late-onset complications of the ketogenic diet for intractable epilepsy. Epilepsia 2004; 45:1116.
  81. Wilson FH, Hariri A, Farhi A, et al. A cluster of metabolic defects caused by mutation in a mitochondrial tRNA. Science 2004; 306:1190.
  82. Sitprija V. Altered fluid, electrolyte and mineral status in tropical disease, with an emphasis on malaria and leptospirosis. Nat Clin Pract Nephrol 2008; 4:91.
  83. Spichler A, Athanazio DA, Furtado J, et al. Case report: severe, symptomatic hypomagnesemia in acute leptospirosis. Am J Trop Med Hyg 2008; 79:915.