Advertisement

Drug Safety

pp 1–14 | Cite as

Drug-Induced Hypophosphatemia: Current Insights

  • Efstathia Megapanou
  • Matilda Florentin
  • Haralampos Milionis
  • Moses Elisaf
  • George LiamisEmail author
Review Article

Abstract

Phosphate is actively involved in many important biochemical pathways, such as energy and nucleic acid metabolism, cellular signaling, and bone formation. Hypophosphatemia, defined as serum phosphate levels below 2.5 mg/dL (0.81 mmol/L), is frequently observed in the course of treatment with commonly used drugs, such as diuretics, bisphosphonates, antibiotics, insulin, and antacids. Furthermore, this undesired effect may complicate the use of several novel medications, including teriparatide, denosumab, parenteral iron, and antiviral and antineoplastic agents. This review addresses drug-associated hypophosphatemia, focusing on underlying mechanisms and the most recent knowledge on this topic, in order to increase the insight of clinicians, with reference to early diagnosis and appropriate management.

Notes

Compliance with Ethical Standards

Conflict of interest

Efstathia Megapanou, Matilda Florentin, Haralampos Milionis, Moses Elisaf, and George Liamis have no conflicts of interest to declare that are directly relevant to the contents of this study.

Funding

No sources of funding were used to assist in the preparation of this study.

References

  1. 1.
    Christov M, Jüppner H. Phosphate homeostasis disorders. Best Pract Res Clin Endocrinol Metab. 2018;32(5):685–706.PubMedCrossRefGoogle Scholar
  2. 2.
    Moe SM. Disorders involving calcium, phosphorus, and magnesium. Prim Care. 2008;35(2):215–37 (v–vi).PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Song L. Calcium and bone metabolism indices. In: Makowski GS, editor. Advances in clinical chemistry, vol. 82. Elsevier: New York; 2017. p. 1–46.Google Scholar
  4. 4.
    Liamis G, Milionis HJ, Elisaf M. Medication-induced hypophosphatemia: a review. QJM. 2010;103(7):449–59.PubMedCrossRefGoogle Scholar
  5. 5.
    Gaasbeek A, Meinders AE. Hypophosphatemia: an update on its etiology and treatment. Am J Med. 2005;118(10):1094–101.PubMedCrossRefGoogle Scholar
  6. 6.
    Choi N-W. Kidney and phosphate metabolism. Electrolyte Blood Press. 2008;6(2):77–85.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Paterson CR. Hypophosphataemia: a dangerous disorder. Nutrition. 1996;12(7–8):540–1.PubMedCrossRefGoogle Scholar
  8. 8.
    Crook MA. Hypophosphataemia and hypokalaemia in patients with hypomagnesaemia. Br J Biomed Sci. 1994;51(1):24–7.Google Scholar
  9. 9.
    Liamis G, Liberopoulos E, Alexandridis G, Elisaf M. Hypomagnesemia in a department of internal medicine. Magnes Res. 2012;25(4):149–58.PubMedGoogle Scholar
  10. 10.
    Milionis HJ, Rizos E, Liamis G, Nikas S, Siamopoulos KC, Elisaf MS. Acid-base and electrolyte disturbances in patients with hypercalcemia. South Med J. 2002;95(11):1280–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Liamis G, Liberopoulos E, Barkas F, Elisaf M. Diabetes mellitus and electrolyte disorders. World J Clin Cases. 2014;16(2):488–96.CrossRefGoogle Scholar
  12. 12.
    Izzedine H, Launay-Vacher V, Isnard-Bagnis C, Deray G. Drug-induced Fanconi’s syndrome. Am J Kidney Dis. 2003;41(2):292–309.PubMedCrossRefGoogle Scholar
  13. 13.
    Goto S, Fujii H, Kono K, Watanabe K, Nakai K, Nishi S. Serum FGF23 levels may not be associated with serum phosphate and 1,25-dihydroxyvitamin D levels in patients with Fanconi syndrome-induced hypophosphatemia. Clin Kidney J. 2016;9(5):677–81.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Liamis G, Milionis HJ, Elisaf M. Pharmacologically-induced metabolic acidosis: a review. Drug Saf. 2010;33(5):371–91.PubMedCrossRefGoogle Scholar
  15. 15.
    Christopoulou EC, Filippatos TD, Megapanou E, Elisaf MS, Liamis G. Phosphate imbalance in patients with heart failure. Heart Fail Rev. 2017;22(3):349–56.CrossRefGoogle Scholar
  16. 16.
    Brotfain E, Schwartz A, Boniel A, Koyfman L, Boyko M, Kutz R, et al. Clinical outcome of critically ill patients with thrombocytopenia and hypophosphatemia in the early stage of sepsis. Anestezjol Intensywna Ter. 2016;48(5):294–9.Google Scholar
  17. 17.
    Ariyoshi N, Nogi M, Ando A, Watanabe H, Umekawa S. Hypophosphatemia-induced cardiomyopathy. Am J Med Sci. 2016;352(3):317–23.PubMedCrossRefGoogle Scholar
  18. 18.
    Liamis G, Liberopoulos E, Barkas F, Elisaf M. Spurious electrolyte disorders: a diagnostic challenge for clinicians. Am J Nephrol. 2013;38(1):50–7.CrossRefGoogle Scholar
  19. 19.
    Ramachandra V, Chandran P, Philip R, Arunaachalam V, Raman GV. Effect of mannitol on intraocular pressure in vitrectomized and nonvitrectomized eyes: a prospective comparative study. J Glaucoma. 2019;28(4):318–20.CrossRefGoogle Scholar
  20. 20.
    Donhowe JM, Freier EF, Wong ET, Steffes MW. Factitious hypophosphatemia related to mannitol therapy. Clin Chem. 1981;27(10):1765–9.PubMedGoogle Scholar
  21. 21.
    Eisenbrey AB, Mathew R, Kiechle FL. Mannitol interference in an automated serum phosphate assay. Clin Chem. 1987;33(12):2308–9.PubMedGoogle Scholar
  22. 22.
    Kawamura H, Tanaka S, Uenami Y, Tani M, Ishitani M, Morii S, et al. Hypophosphatemia occurs with insulin administration during refeeding by total parenteral nutrition in rats. J Med Investig. 2018;65(1.2):50–5.CrossRefGoogle Scholar
  23. 23.
    Bode JC, Zelder O, Rumpelt HJ, Wittkamp U. Depletion of liver adenosine phosphates and metabolic effects of intravenous infusion of fructose or sorbitol in man and in the rat. Eur J Clin Investig. 1973;3(5):436–41.CrossRefGoogle Scholar
  24. 24.
    Liamis G, Filippatos TD, Elisaf MS. Correction of hypovolemia with crystalloid fluids: individualizing infusion therapy. Postgrad Med. 2015;127(4):405–12.PubMedCrossRefGoogle Scholar
  25. 25.
    Liamis G, Mitrogianni Z, Liberopoulos EN, Tsimihodimos V, Elisaf M. Electrolyte disturbances in patients with hyponatremia. Intern Med. 2007;46(11):685–90.PubMedCrossRefGoogle Scholar
  26. 26.
    Liamis G, Megapanou E, Elisaf M, Milionis H. Hyponatremia-inducing drugs. In: Peri A, Thompson CJ, Verbalis JG, editors. Frontiers of hormone research, vol. 52. S. Karger AG: Basel; 2019. p. 167–77.Google Scholar
  27. 27.
    Liamis G, Milionis H, Elisaf M. A review of drug-induced hyponatremia. Am J Kidney Dis. 2008;52(1):144–53.PubMedCrossRefGoogle Scholar
  28. 28.
    Cogan E, Debieve MF, Pepersack T, Abramow M. Natriuresis and atrial natriuretic factor secretion during inappropriate antidiuresis. Am J Med. 1988;84(3):409–18.PubMedCrossRefGoogle Scholar
  29. 29.
    Windpessl M, Mayrbaeurl B, Baldinger C, Tiefenthaller G, Prischl FC, Wallner M, et al. Refeeding syndrome in oncology: report of four cases. World J Oncol. 2017;8(1):25–9.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Şan ES, Erdoğan S, Boşnak M, Şan M. Hypophosphatemia associated risk factors in pediatric intensive care patients. Turk J Pediatr. 2017;59(1):35.PubMedCrossRefGoogle Scholar
  31. 31.
    Marinella MA. Refeeding syndrome: an important aspect of supportive oncology. J Support Oncol. 2009;7(1):11–6.PubMedGoogle Scholar
  32. 32.
    Fuentes E, Yeh DD, Quraishi SA, Johnson EA, Kaafarani H, Lee J, et al. Hypophosphatemia in enterally fed patients in the surgical intensive care unit. Nutr Clin Pract. 2017;32(2):252–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Kraft MD, Btaiche IF, Sacks GS, Kudsk KA. Treatment of electrolyte disorders in adult patients in the intensive care unit. Am J Health Syst Pharm. 2005;62(16):1663–82.PubMedCrossRefGoogle Scholar
  34. 34.
    Shoukat S, Usmani NA, Soetan O, Qureshi F. Euglycemic diabetic ketoacidosis accompanied by severe hypophosphatemia during recovery in a patient with type 2 diabetes being treated with canagliflozin/metformin combination therapy. Clin Diabetes. 2017;35(4):249–51.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Filippatos TD, Tsimihodimos V, Liamis G, Elisaf MS. SGLT2 inhibitors-induced electrolyte abnormalities: an analysis of the associated mechanisms. Diabetes Metab Syndr. 2018;12(1):59–63.PubMedCrossRefGoogle Scholar
  36. 36.
    Arroliga AC, Guntupalli KK, Beaver JS, Langholff W, Marino K, Kelly K. Pharmacokinetics and pharmacodynamics of six epoetin alfa dosing regimens in anemic critically ill patients without acute blood loss. Crit Care Med. 2009;37(4):1299–307.PubMedCrossRefGoogle Scholar
  37. 37.
    Tsimberidou AM, O’Brien SM, Cortes JE, Faderl S, Andreeff M, Kantarjian HM, et al. Phase II study of fludarabine, cytarabine (Ara-C), cyclophosphamide, cisplatin and GM-CSF (FACPGM) in patients with Richter’s syndrome or refractory lymphoproliferative disorders. Leuk Lymphoma. 2002;43(4):767–72.PubMedCrossRefGoogle Scholar
  38. 38.
    Body JJ, Cryer PE, Offord KP, Heath H. Epinephrine is a hypophosphatemic hormone in man. Physiological effects of circulating epinephrine on plasma calcium, magnesium, phosphorus, parathyroid hormone, and calcitonin. J Clin Investig. 1983;71(3):572–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Ljunghall S, Joborn H, Rastad J, Akerström G. Plasma potassium and phosphate concentrations-influence by adrenaline infusion, β-blockade and physical exercise. Acta Med Scand. 2009;221(1):83–93.CrossRefGoogle Scholar
  40. 40.
    Prince RL, Monk KJ, Kent GN, Dick I, Thompson PJ. Effects of theophylline and salbutamol on phosphate and calcium metabolism in normal subjects. Miner Electrolyte Metab. 1988;14(5):262–5.PubMedGoogle Scholar
  41. 41.
    Flack JM, Ryder KW, Strickland D, Whang R. Metabolic correlates of theophylline therapy: a concentration-related phenomenon. Ann Pharmacother. 1994;28(2):175–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Brady HR, Ryan F, Cunningham J, Tormey W, Ryan MP, O’Neill S. Hypophosphatemia complicating bronchodilator therapy for acute severe asthma. Arch Intern Med. 1989;149(10):2367–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Aibiki M, Kawaguchi S, Maekawa N. Reversible hypophosphatemia during moderate hypothermia therapy for brain-injured patients. Crit Care Med. 2001;29(9):1726–30.PubMedCrossRefGoogle Scholar
  44. 44.
    Hu C-Y, Lee B-J, Cheng H-F, Wang C-Y. Acetazolamide-related life-threatening hypophosphatemia in a glaucoma patient. J Glaucoma. 2015;24(4):e31–3.PubMedCrossRefGoogle Scholar
  45. 45.
    Itescu S, Haskell LP, Tannenberg AM. Thiazide-induced clinically significant hypophosphatemia. Clin Nephrol. 1987;27(3):161–2.PubMedGoogle Scholar
  46. 46.
    Plante GE, Lafreniere MC, Tam PT, Sirois P. Effect of indapamide on phosphate metabolism and vascular reactivity. Am J Med. 1988;84(1B):26–30.CrossRefGoogle Scholar
  47. 47.
    Ben Salem C, Hmouda H, Bouraoui K. Drug-induced hypokalaemia. Curr Drug Saf. 2009;4(1):55–61.PubMedCrossRefGoogle Scholar
  48. 48.
    Atsmon J, Dolev E. Drug-induced hypomagnesaemia: scope and management. Drug Saf. 2005;28(9):763–88.PubMedCrossRefGoogle Scholar
  49. 49.
    Liamis G, Milionis H, Elisaf M. Blood pressure drug therapy and electrolyte disturbances. Int J Clin Pract. 2008;62(10):1572–80.PubMedCrossRefGoogle Scholar
  50. 50.
    Milionis HJ, Alexandrides GE, Liberopoulos EN, Bairaktari ET, Goudevenos J, Elisaf MS. Hypomagnesemia and concurrent acid-base and electrolyte abnormalities in patients with congestive heart failure. Eur J Heart Fail. 2002;4(2):167–73.PubMedCrossRefGoogle Scholar
  51. 51.
    Clinkenbeard EL, White KE. Systemic control of bone homeostasis by FGF23 signaling. Curr Mol Biol Rep. 2016;2(1):62–71.PubMedCentralCrossRefPubMedGoogle Scholar
  52. 52.
    Andrukhova O, Zeitz U, Goetz R, Mohammadi M, Lanske B, Erben RG. FGF23 acts directly on renal proximal tubules to induce phosphaturia through activation of the ERK1/2-SGK1 signaling pathway. Bone. 2012;51(3):621–8.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Bager P, Hvas CL, Dahlerup JF. Drug-specific hypophosphatemia and hypersensitivity reactions following different intravenous iron infusions. Br J Clin Pharmacol. 2017;83(5):1118–25.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Schaefer B, Würtinger P, Finkenstedt A, Braithwaite V, Viveiros A, Effenberger M, et al. Choice of high-dose intravenous iron preparation determines hypophosphatemia risk. PLoS One. 2016;11(12):e0167146.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Wolf M, Chertow GM, Macdougall IC, Kaper R, Krop J, Strauss W. Randomized trial of intravenous iron-induced hypophosphatemia. JCI Insight. 2018;3(23):124486.PubMedCrossRefGoogle Scholar
  56. 56.
    Auerbach M, Chertow GM, Rosner M. Ferumoxytol for the treatment of iron deficiency anemia. Expert Rev Hematol. 2018;11(10):829–34.CrossRefGoogle Scholar
  57. 57.
    Zoller H, Schaefer B, Glodny B. Iron-induced hypophosphatemia: an emerging complication. Curr Opin Nephrol Hypertens. 2017;26(4):266–75.PubMedCrossRefGoogle Scholar
  58. 58.
    Hardy S, Vandemergel X. Intravenous iron administration and hypophosphatemia in clinical practice. Int J Rheumatol. 2015;2015:468675.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Detlie TE, Lindstrøm JC, Jahnsen ME, Finnes E, Zoller H, Moum B, Jahnsen J. Incidence of hypophosphatemia in patients with inflammatory bowel disease treated with ferric carboxymaltose or iron isomaltoside. Aliment Pharmacol Ther. 2019;50(4):397–406.PubMedCrossRefGoogle Scholar
  60. 60.
    Blazevic A, Hunze J, Boots JMM. Severe hypophosphataemia after intravenous iron administration. Neth J Med. 2014;72(1):49–53.PubMedGoogle Scholar
  61. 61.
    Kalra P, Bhandari S. Efficacy and safety of iron isomaltoside (Monofer®) in the management of patients with iron deficiency anemia. Int J Nephrol Renovasc Dis. 2016;9:53–64.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Smyth B, Ong S. Severe hypocalcaemia and hypophosphataemia following intravenous iron and denosumab: a novel drug interaction. Intern Med J. 2016;46(3):360–3.PubMedCrossRefGoogle Scholar
  63. 63.
    Imel EA, Econs MJ. Approach to the hypophosphatemic patient. J Clin Endocrinol Metab. 2012;97(3):696–706.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Stöhr R, Sandstede L, Heine GH, Marx N, Brandenburg V. High-dose ferric carboxymaltose in patients with HFrEF induces significant hypophosphatemia. J Am Coll Cardiol. 2018;71(19):2270–1.PubMedCrossRefGoogle Scholar
  65. 65.
    Yoshida T, Taguchi D, Fukuda K, Shimazu K, Inoue M, Murata K, et al. Incidence of hypophosphatemia in advanced cancer patients: a recent report from a single institution. Int J Clin Oncol. 2017;22(2):244–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Liamis G, Filippatos TD, Elisaf MS. Electrolyte disorders associated with the use of anticancer drugs. Eur J Pharmacol. 2016;777:78–87.PubMedCrossRefGoogle Scholar
  67. 67.
    Mir O, Coriat R, Boudou-Rouquette P, Durand JP, Goldwasser F. Sorafenib-induced diarrhea and hypophosphatemia: mechanisms and therapeutic implications. Ann Oncol. 2012;23(1):280–1.PubMedCrossRefGoogle Scholar
  68. 68.
    Giles FJ, Kantarjian HM, Ie Coutre PD, Baccarani M, Mahon F-X, Blakesley RE, et al. Nilotinib is effective in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blastic phase. Leukemia. 2012;26(5):959–62.PubMedCrossRefGoogle Scholar
  69. 69.
    Jin H, Zhang J, Shen K, Hao J, Feng Y, Yuan C, et al. Efficacy and safety of perioperative appliance of sunitinib in patients with metastatic or advanced renal cell carcinoma: a systematic review and meta-analysis. Medicine (Baltimore). 2019;98(20):e15424.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Wanchoo R, Jhaveri KD, Deray G, Launay-Vacher V. Renal effects of BRAF inhibitors: a systematic review by the Cancer and the Kidney International Network. Clin Kidney J. 2016;9(2):245–51.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Bellini E, Pia A, Brizzi MP, Tampellini M, Torta M, Terzolo M, et al. Sorafenib may induce hypophosphatemia through a fibroblast growth factor-23 (FGF23)-independent mechanism. Ann Oncol. 2011;22(4):988–90.PubMedCrossRefGoogle Scholar
  72. 72.
    Wysokinska EM, Thompson AM, Franco Palacios CR. A case of hypophosphatemia with increased urinary excretion of phosphorus associated with ibrutinib. Case Rep Oncol. 2016;9(1):223–7.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Patt Y, Rojas-Hernandez C, Fekrazad HM, Bansal P, Lee FC. Phase II trial of sorafenib in combination with capecitabine in patients with hepatocellular carcinoma: iNST 08-20. Oncologist. 2017;22(10):1158-e116.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Grignani G, Palmerini E, Ferraresi V, D’Ambrosio L, Bertulli R, Asaftei SD, et al. Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial. Lancet Oncol. 2015;16(1):98–107.PubMedCrossRefGoogle Scholar
  75. 75.
    Zhang Z, Jiang T, Wang W, Piao D. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumor after failure with imatinib and sunitinib treatment: a meta-analysis. Medicine (Baltimore). 2017;96(48):e8698.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Duffaud F, Mir O, Boudou-Rouquette P, Piperno-Neumann S, Penel N, Bompas E, et al. Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: a non-comparative, randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 2019;20(1):120–33.PubMedCrossRefGoogle Scholar
  77. 77.
    Yin X, Yin Y, Shen C, Chen H, Wang J, Cai Z, et al. Adverse events risk associated with regorafenib in the treatment of advanced solid tumors: meta-analysis of randomized controlled trials. Oncotargets Ther. 2018;11:6405–14.CrossRefGoogle Scholar
  78. 78.
    Abbas A, Mirza MM, Ganti AK, Tendulkar K. Renal toxicities of targeted therapies. Target Oncol. 2015;10(4):487–99.PubMedCrossRefGoogle Scholar
  79. 79.
    Shaw AT, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014;370(26):2537–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Morgan RJ, Synold TW, Longmate JA, Quinn DI, Gandara D, Lenz H-J, et al. Pharmacodynamics (PD) and pharmacokinetics (PK) of E7389 (eribulin, halichondrin B analog) during a phase I trial in patients with advanced solid tumors: a California Cancer Consortium trial. Cancer Chemother Pharmacol. 2015;76(5):897–907.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Evans TRJ, Dean E, Molife LR, Lopez J, Ranson M, El-Khouly F, et al. Phase 1 dose-finding and pharmacokinetic study of eribulin-liposomal formulation in patients with solid tumours. Br J Cancer. 2019;120(4):379–86.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Sakurada H, Kawase Y, Mizuno H, Naito K, Yamamura M. A case of hypophosphatemia induced by administration of amrubicin in a patient with small cell lung cancer (in Japanese). Gan To Kagaku Ryoho. 2018;45(9):1369–71.PubMedGoogle Scholar
  83. 83.
    Tataranni T, Biondi G, Cariello M, Mangino M, Colucci G, Rutigliano M, et al. Rapamycin-induced hypophosphatemia and insulin resistance are associated with mTORC2 activation and Klotho expression. Am J Transplant. 2011;11(8):1656–64.PubMedCrossRefGoogle Scholar
  84. 84.
    Oberlin O, Fawaz O, Rey A, Niaudet P, Ridola V, Orbach D, et al. Long-term evaluation of Ifosfamide-related nephrotoxicity in children. J Clin Oncol. 2009;27(32):5350–5.PubMedCrossRefGoogle Scholar
  85. 85.
    Stava CJ, Jimenez C, Hu MI, Vassilopoulou-Sellin R. Skeletal sequelae of cancer and cancer treatment. J Cancer Surviv. 2009;3(2):75–88.PubMedCrossRefGoogle Scholar
  86. 86.
    Chen L, Xiong X, Hou X, Wei H, Zhai J, Xia T, et al. Wuzhi capsule regulates chloroacetaldehyde pharmacokinetics behaviour and alleviates high-dose cyclophosphamide-induced nephrotoxicity and neurotoxicity in rats. Basic Clin Pharmacol Toxicol. 2019;125(2):142–51.PubMedGoogle Scholar
  87. 87.
    Perazella MA. Onco-nephrology: renal toxicities of chemotherapeutic agents. Clin J Am Soc Nephrol. 2012;7(10):1713–21.PubMedCrossRefGoogle Scholar
  88. 88.
    Oronsky B, Caroen S, Oronsky A, Dobalian VE, Oronsky N, Lybeck M, et al. Electrolyte disorders with platinum-based chemotherapy: mechanisms, manifestations and management. Cancer Chemother Pharmacol. 2017;80(5):895–907.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Elazzazy S, El-Geed HA, Al Yafei S. Severe hypophosphatemia induced after first cycle of the ESHAP protocol for Hodgkin’s lymphoma: a case report. Int Med Case Rep J. 2013;6:1–5.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Reinert RB, Bixby D, Koenig RJ. Fibroblast growth factor 23-induced hypophosphatemia in acute leukemia. J Endocr Soc. 2018;2(5):437–43.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Caras JA. Spurious hypophosphatemia associated with multiple myeloma. Endocr Pract. 1997;3(3):135–6.PubMedCrossRefGoogle Scholar
  92. 92.
    Tolman KG, Jubiz W, Sannella JJ, Madsen JA, Belsey RE, Goldsmith RS, et al. Osteomalacia associated with anticonvulsant drug therapy in mentally retarded children. Pediatrics. 1975;56(1):45–50.PubMedGoogle Scholar
  93. 93.
    Smith GC, Balfe JW, Kooh SW. Anticonvulsants as a cause of Fanconi syndrome. Nephrol Dial. 1995;10(4):543–5.CrossRefGoogle Scholar
  94. 94.
    Heidari R, Jafari F, Khodaei F, Shirazi Yeganeh B, Niknahad H. Mechanism of valproic acid-induced Fanconi syndrome involves mitochondrial dysfunction and oxidative stress in rat kidney: valproic acid-induced Fanconi syndrome. Nephrology. 2018;23(4):351–61.PubMedCrossRefGoogle Scholar
  95. 95.
    Barras P, Siclari F, Hügli O, Rossetti AO, Lamy O, Novy J. A potential role of hypophosphatemia for diagnosing convulsive seizures: a case–control study. Epilepsia. 2019;60(8):1580–5.PubMedCrossRefGoogle Scholar
  96. 96.
    Alexandridis G, Liberopoulos E, Elisaf M. Aminoglycoside-induced reversible tubular dysfunction. Pharmacology. 2003;67(3):118–20.PubMedCrossRefGoogle Scholar
  97. 97.
    Decaux G. Tetracycline-induced renal hypophosphatemia in a patient with a syndrome of inappropriate secretion of antidiuretic hormone. Nephron. 1988;48(1):40–2.PubMedCrossRefGoogle Scholar
  98. 98.
    Cheng C-Y, Chang S-Y, Lin M-H, Ku S-Y, Sun N-L, Cheng S-H. Tenofovir disoproxil fumarate-associated hypophosphatemia as determined by fractional excretion of filtered phosphate in HIV-infected patients. J Infect Chemother. 2016;22(11):744–7.PubMedCrossRefGoogle Scholar
  99. 99.
    Saeedi R, Jiang SY, Holmes DT, Kendler DL. Fibroblast growth factor 23 is elevated in tenofovir-related hypophosphatemia. Calcif Tissue Int. 2014;94(6):665–8.CrossRefGoogle Scholar
  100. 100.
    Lee Y-S, Kim B-K, Lee H-J, Dan J. Pathologic femoral neck fracture due to fanconi syndrome induced by adefovir dipivoxil therapy for hepatitis B. Clin Orthop Surg. 2016;8(2):232.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Shimizu Y, Hiraoka A, Yamago H, Shiraishi A, Imai Y, Tatsukawa H, et al. Hypophosphatemia in patients with hepatitis B virus infection undergoing long-term adefovir dipivoxil therapy. Hepatol Res. 2014;44(11):1081–7.PubMedCrossRefGoogle Scholar
  102. 102.
    Tanaka M, Suzuki F, Seko Y, Hara T, Kawamura Y, Sezaki H, et al. Renal dysfunction and hypophosphatemia during long-term lamivudine plus adefovir dipivoxil therapy in patients with chronic hepatitis B. J Gastroenterol. 2014;49(3):470–80.PubMedCrossRefGoogle Scholar
  103. 103.
    Wei Z, He J, Fu W, Zhang Z. Osteomalacia induced by long-term low-dose adefovir dipivoxil: clinical characteristics and genetic predictors. Bone. 2016;93:97–103.PubMedCrossRefGoogle Scholar
  104. 104.
    Yamamoto T, Maruyama Y, Ohashi N, Yasuda H, Shinozaki M. Hypophosphatemia predicts a failure to recover from adefovir-related renal injury after dose reduction in lamivudine-resistant hepatitis B patients. Hepatol Res. 2017;47(12):1272–81.PubMedCrossRefGoogle Scholar
  105. 105.
    Kichloo A, Chugh SS, Gupta S, Panday J, Goldar GE. Tenofovir and severe symptomatic hypophosphatemia. J Investig Med High Impact Case Rep. 2019;7:2324709619848796.PubMedPubMedCentralGoogle Scholar
  106. 106.
    Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J. Is Tenofovir alafenamide safer than tenofovir disoproxil fumarate for the kidneys? AIDS Rev. 2016;18(4):184–92.PubMedGoogle Scholar
  107. 107.
    Kahn J, Lagakos S, Wulfsohn M, Cherng D, Miller M, Cherrington J, et al. Efficacy and safety of adefovir dipivoxil with antiretroviral therapy: a randomized controlled trial. JAMA. 1999;282(24):2305–12.PubMedCrossRefGoogle Scholar
  108. 108.
    Qian Y-Y, Dai Z-J, Ruan L-Y, Pan Y-J, Jin J, Shi M-T, et al. Low-dose adefovir dipivoxil-induced hypophosphatemia osteomalacia in five chronic hepatitis B virus-infected patients. Is low-dose adefovir dipivoxil-induced nephrotoxicity completely reversible? Drug Des Dev Ther. 2019;13:1127–33.CrossRefGoogle Scholar
  109. 109.
    Gupta SK, Yeh E, Kitch DW, Brown TT, Venuto CS, Morse GD, et al. Bone mineral density reductions after tenofovir disoproxil fumarate initiation and changes in phosphaturia: a secondary analysis of ACTG A5224s. J Antimicrob Chemother. 2017;72(7):2042–8.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Adedeji TA, Adebisi SA, Adedeji NO, Biliaminu SA, Olanrewaju TO. Effects of highly active antiretroviral therapy on renal function and renal phosphate handling in african adults with advanced HIV and CKD. Infect Disord Drug Targets. 2019;19(1):88–100.PubMedCrossRefGoogle Scholar
  111. 111.
    Hariparsad N, Nallani SC, Sane RS, Buckley DJ, Buckley AR, Desai PB. Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and phenobarbital. J Clin Pharmacol. 2004;44(11):1273–81.PubMedCrossRefGoogle Scholar
  112. 112.
    Bonjoch A, Puig J, Pérez-Alvarez N, Juega J, Echeverría P, Clotet B, et al. Impact of protease inhibitors on the evolution of urinary markers: subanalyses from an observational cross-sectional study. Medicine (Baltimore). 2016;95(32):4507.CrossRefGoogle Scholar
  113. 113.
    Koklu S, Gulsen MT, Tuna Y, Koklu H, Yurksel O, Demir M, et al. Differences in nephrotoxicity risk and renal effects among anti-viral therapies against hepatitis B. Aliment Pharmacol Ther. 2015;41(3):310–9.PubMedCrossRefGoogle Scholar
  114. 114.
    Saeedi R, Mojebi-Mogharar A, Sandhu SK, Dubland JA, Ford J-A, Yousefi M, et al. Lamivudine, entecavir, or tenofovir treatment of hepatitis b infection: effects on calcium, phosphate, FGF23 and indicators of bone metabolism. Ann Hepatol. 2017;16(2):207–14.PubMedCrossRefGoogle Scholar
  115. 115.
    Andrade L, Rebouças NA, Seguro AC. Down-regulation of Na+ transporters and AQP2 is responsible for acyclovir-induced polyuria and hypophosphatemia. Kidney Int. 2004;65(1):175–83.PubMedCrossRefGoogle Scholar
  116. 116.
    Monteiro JL, De Castro I, Seguro AC. Hypophosphatemia induced by acyclovir. Transplantation. 1993;55(3):680–2.PubMedGoogle Scholar
  117. 117.
    Nasomyont N, Hornung LN, Gordon CM, Wasserman H. Outcomes following intravenous bisphosphonate infusion in pediatric patients: a 7-year retrospective chart review. Bone. 2019;121:60–7.PubMedCrossRefGoogle Scholar
  118. 118.
    Kaur U, Chakrabarti SS, Gambhir IS. Zoledronate induced hypocalcemia and hypophosphatemia in osteoporosis: a cause of concern. Curr Drug Saf. 2016;11(3):267–9.PubMedCrossRefGoogle Scholar
  119. 119.
    Clark SL, Nystrom EM. A case of severe, prolonged, refractory hypophosphatemia after zoledronic acid administration. J Pharm Pract. 2016;29(2):172–6.PubMedCrossRefGoogle Scholar
  120. 120.
    Elisaf M, Kalaitzidis R, Siamopoulos KC. Multiple electrolyte abnormalities after pamidronate administration. Nephron. 1998;79(3):337–9.PubMedCrossRefGoogle Scholar
  121. 121.
    Nguyen A, Kalis JA, Sutz TR, Jeffers KD. Development of a practice standard for monitoring adult patients receiving bone-modifying agents at a community cancer center. J Adv Pract Oncol. 2018;9(6):601–7.PubMedPubMedCentralGoogle Scholar
  122. 122.
    Chung T-L, Chen N-C, Chen C-L. Severe hypophosphatemia induced by denosumab in a patient with osteomalacia and tenofovir disoproxil fumarate-related acquired Fanconi syndrome. Osteoporos Int. 2019;30(2):519–23.PubMedCrossRefGoogle Scholar
  123. 123.
    Masuda H, Kaga K, Inahara M, Araki K, Kojima S, Naya Y, et al. Severe hypophosphatemia following denosumab administration in a hemodialysis patient with progressive prostate cancer. Urol Case Rep. 2017;13:63–5.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Gralow JR, Biermann JS, Farooki A, Fornier MN, Gagel RF, Kumar R, et al. NCCN Task Force Report: bone health in cancer care. J Natl Compr Cancer Netw. 2013;11(Suppl 3):S1–50 (quiz S51).CrossRefGoogle Scholar
  125. 125.
    Van Poznak CH, Termin S, Yee GC, Janjan NA, Barlow WE, Biermann JS, et al. American Society of Clinical Oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer. J Clin Oncol. 2011;29(9):1221–7.PubMedCrossRefGoogle Scholar
  126. 126.
    Hajime M, Okada Y, Mori H, Tanaka Y. A case of teriparatide-induced severe hypophosphatemia and hypercalcemia. J Bone Miner Metab. 2014;32(5):601–4.PubMedCrossRefGoogle Scholar
  127. 127.
    Faroqui S, Levi M, Soleimani M, Amlal H. Estrogen downregulates the proximal tubule type IIa sodium phosphate cotransporter causing phosphate wasting and hypophosphatemia. Kidney Int. 2008;73(10):1141–50.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Bech AP, Hoorn EJ, Zietse R, Wetzels JFM, Nijenhuis T. Yield of diagnostic tests in unexplained renal hypophosphatemia: a case series. BMC Nephrol. 2018;19(1):220.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Patil S, Subramany S, Patil S, Gurram P, Singh M, Krause M. Ibuprofen abuse—a case of rhabdomyolysis, hypokalemia, and hypophosphatemia with drug-induced mixed renal tubular acidosis. Kidney Int Rep. 2018;3(5):1237–8.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Cadman PE. Hypophosphatemia in users of cannabis. Am J Kidney Dis. 2017;69(1):152–5.CrossRefGoogle Scholar
  131. 131.
    Elisaf M, Merkouropoulos M, Tsianos EV, Siamopoulos KC. Acid-base and electrolyte abnormalities in alcoholic patients. Miner Electrolyte Metab. 1994;20(5):274–81.Google Scholar
  132. 132.
    Bissell BD, Davis JE, Flannery AH, Adkins DA, Thompson Bastin ML. Aggressive treatment of life-threatening hypophosphatemia during recovery from fulminant hepatic failure: a case report. J Intensive Care Med. 2018;33(6):375–9.PubMedCrossRefGoogle Scholar
  133. 133.
    Jones AF, Harvey JM, Vale JA. Hypophosphataemia and phosphaturia in paracetamol poisoning. Lancet. 1989;2(8663):608–9.PubMedCrossRefGoogle Scholar
  134. 134.
    Schmidt LE, Dalhoff K. Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity. Hepatology. 2002;36(3):659–65.PubMedCrossRefGoogle Scholar
  135. 135.
    Wolansky LJ, Cadavid D, Punia V, Kim S, Cheriyan J, Haghighi M, et al. Hypophosphatemia is associated with the serial administration of triple-dose gadolinium to patients for brain MRI: hypophosphatemia from serial, 3-dose gadolinium. J Neuroimaging. 2015;25(3):379–83.PubMedCrossRefGoogle Scholar
  136. 136.
    Chines A, Pacifici R. Antacid and sucralfate-induced hypophosphatemic osteomalacia: a case report and review of the literature. Calcif Tissue Int. 1990;47(5):291–5.PubMedCrossRefGoogle Scholar
  137. 137.
    Maccubbin D, Tipping D, Kuznetsova O, Hanlon WA, Bostom AG. Hypophosphatemic effect of niacin in patients without renal failure: a randomized trial. Clin J Am Soc Nephrol. 2010;5(4):582–9.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Ginsberg C, Ix JH. Nicotinamide and phosphate homeostasis in chronic kidney disease. Curr Opin Nephrol Hypertens. 2016;25(4):285–91.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Raschka C, Koch HJ. Longterm treatment of psoriasis using fumaric acid preparations can be associated with severe proximal tubular damage. Hum Exp Toxicol. 1999;18(12):738–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Internal Medicine, School of MedicineUniversity of IoanninaIoanninaGreece

Personalised recommendations