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Prevention of hypomagnesemia in critically ill patients with acute kidney injury on continuous kidney replacement therapy: the role of early supplementation and close monitoring

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Abstract

Hypomagnesemia is a common electrolyte disorder in critically ill patients and is associated with increased morbidity and mortality risk. Many clinical conditions may contribute to hypomagnesemia through different pathogenetic mechanisms. In patients with acute kidney injury (AKI) the need for continuous or prolonged intermittent kidney replacement therapy (CKRT and PIKRT, respectively) may further add to other causes of hypomagnesemia, especially when regional citrate anticoagulation (RCA) is used. The basic principle of RCA is chelation of ionized calcium by citrate within the extracorporeal circuit, thus blocking the coagulation cascade. Magnesium, a divalent cation, follows the same fate as calcium; the amount lost in the effluent includes both magnesium-citrate complexes and the free fraction directly diffusing through the hemofilter. While increasing the magnesium content of dialysis/replacement solutions may decrease the risk of hypomagnesemia, the optimal concentration for the variable combination of solutions adopted in different KRT protocols has not yet been identified. An alternative and effective approach is based on including early intravenous magnesium supplementation in the KRT protocol, and close monitoring of serum magnesium levels, especially in the setting of RCA. Thus, strategies aimed at precisely tailoring both dialysis prescriptions and the composition of KRT fluids, as well as early magnesium supplementation and close monitoring, could represent a cornerstone in reducing KRT-related hypomagnesemia.

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References

  1. Jahnen-Dechent W, Ketteler M (2012) Magnesium basics. Clin Kidney J 5:(Suppl 1):i3–i14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Escuela MP, Guerra M, Añón JM et al (2005) Total and ionized serum magnesium in critically ill patients. Intensive Care Med 31(1):151–156

    Article  PubMed  Google Scholar 

  3. Hansen BA, Bruserud Ø (2018) Hypomagnesemia in critically ill patients. J Intensive Care 6:21

    Article  PubMed  PubMed Central  Google Scholar 

  4. Huijgen HJ, Soesan M, Sanders R, Mairuhu WM, Kesecioglu J, Sanders GT (2000) Magnesium levels in critically ill patients. What should we measure? Am J Clin Pathol 114(5):688–695

    Article  CAS  PubMed  Google Scholar 

  5. Saris NE, Mervaala E, Karppanen H, Khawaja JA, Lewenstam A (2000) Magnesium. An update on physiological, clinical and analytical aspects. Clin Chim Acta 294(1–2):1–26

    Article  CAS  PubMed  Google Scholar 

  6. Magnesium in Coronaries (MAGIC) Trial Investigators (2002) Early administration of intravenous magnesium to high-risk patients with acute myocardial infarction in the magnesium in coronaries (MAGIC) trial: a randomised controlled trial. Lancet 360(9341):1189–1196

    Article  Google Scholar 

  7. de Baaij JH, Hoenderop JG, Bindels RJ (2015) Magnesium in man: implications for health and disease. Physiol Rev 95(1):1–46

    Article  PubMed  CAS  Google Scholar 

  8. Feillet-Coudray C, Coudray C, Gueux E et al (2003) A new in vitro blood load test using a magnesium stable isotope for assessment of magnesium status. J Nutr 133:1220–1223

    Article  CAS  PubMed  Google Scholar 

  9. Ahmed F, Mohammed A (2019) Magnesium: the forgotten electrolyte—a review on hypomagnesemia. Med Sci (Basel) 7(4):56

    Google Scholar 

  10. van der Wijst J, Belge H, Bindels RJM, Devuyst O (2019) Learning physiology from inherited kidney disorders. Phys Rev 99(3):1575–1653

    Google Scholar 

  11. Schaffers OJM, Hooenderop JGJ, Bindels RJM, de Baij JHF (2018) The rise and fall of novel renal magnesium transporters. Am J Physiol Ren Physiol 314:1027–1033

    Article  CAS  Google Scholar 

  12. Topf JM, Murray PT (2003) Hypomagnesemia and hypermagnesemia. Rev Endocr Metab Disord 4(2):195–206

    Article  PubMed  Google Scholar 

  13. Felsenfeld AJ, Levine BS, Rodriguez M (2015) Pathophysiology of calcium, phosphorus, and magnesium dysregulation in chronic kidney disease. Semin Dial 28(6):564–577

    Article  PubMed  Google Scholar 

  14. Misra PS, Nessim SJ (2017) Clinical aspects of magnesium physiology in patients on dialysis. Semin Dial 30(5):438–445

    Article  PubMed  Google Scholar 

  15. Tong GM, Rude RK (2005) Magnesium deficiency in critical illness. J Intensive Care Med 20(1):3–17

    Article  PubMed  Google Scholar 

  16. Soliman HM, Mercan D, Lobo SS, Mélot C, Vincent JL (2003) Development of ionized hypomagnesemia is associated with higher mortality rates. Crit Care Med 31(4):1082–1087

    Article  CAS  PubMed  Google Scholar 

  17. Upala S, Jaruvongvanich V, Wijarnpreecha K, Sanguankeo A (2016) Hypomagnesemia and mortality in patients admitted to intensive care unit: a systematic review and meta-analysis. QJM 109(7):453–459

    Article  PubMed  Google Scholar 

  18. Velissaris D, Karamouzos V, Pierrakos C, Aretha D, Karanikolas M (2015) Hypomagnesemia in critically ill sepsis patients. J Clin Med Res 7(12):911–918

    Article  PubMed  PubMed Central  Google Scholar 

  19. Watanabe M, Shinohara A, Matsukawa T et al (2011) Chronic magnesium deficiency decreases tolerance to hypoxia/reoxygenation injury in mouse heart. Life Sci 88(15–16):658–663

    Article  CAS  PubMed  Google Scholar 

  20. Fiaccadori E, Del Canale S, Coffrini E et al (1988) Muscle and serum magnesium in pulmonary intensive care unit patients. Crit Care Med 16(8):751–760

    Article  CAS  PubMed  Google Scholar 

  21. Klein JC, Moser-Veillon PB, Schweitzer A et al (2002) Magnesium, calcium, zinc, and nitrogen loss in trauma patients during continuous renal replacement therapy. JPEN J Parenter Enter Nutr 26(2):77–93

    Article  CAS  Google Scholar 

  22. Cundy T, Dissanayake A (2008) Severe hypomagnesaemia in long-term users of proton-pump inhibitors. Clin Endocrinol 69(2):338–434

    Article  CAS  Google Scholar 

  23. Regolisti G, Cabassi A, Parenti E, Maggiore U, Fiaccadori E (2010) Severe hypomagnesemia during long-term treatment with a proton pump inhibitor. Am J Kidney Dis 56(1):168–174

    Article  PubMed  Google Scholar 

  24. Gröber U (2019) Magnesium and drugs. Int J Mol Sci 20(9):2094

    Article  CAS  PubMed Central  Google Scholar 

  25. Thongon N, Krishnamra N (2012) Apical acidity decreases inhibitory effect of omeprazole on Mg(2+) absorption and claudin-7 and -12 expression in Caco-2 monolayers. Exp Mol Med 44(11):684–693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Perazella MA (2013) Proton pump inhibitors and hypomagnesemia: a rare but serious complication. Kidney Int 83(4):553–556

    Article  CAS  PubMed  Google Scholar 

  27. Boot R, Koekkoek KW, van Zanten AR (2018) Refeeding syndrome: relevance for the critically ill patient. Curr Opin Crit Care 24(4):235–240

    Article  PubMed  Google Scholar 

  28. Pham PCT, Pham PM, Pham SV, Miller JM, Pham PTT (2007) Hypomagnesemia in patients with type 2 diabetes. Clin J Am Soc Nephrol 2:366–373

    Article  CAS  PubMed  Google Scholar 

  29. Alexander RT, Hoenderop JG, Bindels RJ (2008) Molecular determinants of magnesium homeostasis: insights from human disease. J Am Soc Nephrol 19(8):1451–1458

    Article  CAS  PubMed  Google Scholar 

  30. Loupy A, Ramakrishnan SK, Wootla B et al (2012) PTH-independent regulation of blood calcium concentration by the calcium-sensing receptor. J Clin Investig 122(9):3355–3367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pham PC, Pham PA, Pham SV, Pham PT, Pham PM, Pham PT (2014) Hypomagnesemia: a clinical perspective. Int J Nephrol Renovasc Dis 7:219–230

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Morimatsu H, Uchino S, Bellomo R, Ronco C (2002) Continuous veno-venous hemodiafiltration or hemofiltration: impact on calcium, phosphate and magnesium concentrations. Int J Artif Organs 25(6):512–519

    Article  CAS  PubMed  Google Scholar 

  33. Morgera S, Schneider M, Slowinski T et al (2009) A safe citrate anticoagulation protocol with variable treatment efficacy and excellent control of the acid-base status. Crit Care Med 37(6):2018–2024

    Article  CAS  PubMed  Google Scholar 

  34. Brain M, Anderson M, Parkes S, Fowler P (2012) Magnesium flux during continuous venovenous haemodiafiltration with heparin and citrate anticoagulation. Crit Care Resusc 14(4):274–282

    PubMed  Google Scholar 

  35. Leung AK, Shum HP, Chan KC, Chan SC, Lai KY, Yan WW (2013) A retrospective review of the use of regional citrate anticoagulation in continuous venovenous hemofiltration for critically ill patients. Crit Care Res Pract 2013:349512

    PubMed  PubMed Central  Google Scholar 

  36. Morabito S, Pistolesi V, Tritapepe L, Fiaccadori E (2014) Regional citrate anticoagulation for RRTs in critically ill patients with AKI. Clin J Am Soc Nephrol 9(12):2173–2188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zakharchenko M, Leden P, Rulíšek J, Los F, Brodska H, Balik M (2016) Ionized magnesium and regional citrate anticoagulation for continuous renal replacement therapy. Blood Purif 41(1–3):41–47

    Article  CAS  PubMed  Google Scholar 

  38. Fani F, Regolisti G, Delsante M et al (2018) Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury. J Nephrol 31(3):351–359

    Article  CAS  PubMed  Google Scholar 

  39. Li PK, Burdmann EA, Mehta RL, World Kidney Day Steering C (2013) Acute kidney injury: global health alert. Kidney Int 83(3):372–376

    Article  PubMed  Google Scholar 

  40. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl S2:1–138

    Google Scholar 

  41. Uchino S, Bellomo R, Morimatsu H et al (2007) Continuous renal replacement therapy: a worldwide practice survey. The beginning and ending supportive therapy for the kidney (B.E.S.T. study) investigators. Intensive Care Med 33(9):1563–1570

    Article  PubMed  Google Scholar 

  42. Marshall MR, Golper TA (2011) Low-efficiency acute renal replacement therapy: role in acute kidney injury. Semin Dial 24(2):142–148

    Article  PubMed  Google Scholar 

  43. Tolwani A (2012) Continuous renal replacement therapy for acute kidney injury. N Engl J Med 367(26):2505–2514

    Article  CAS  PubMed  Google Scholar 

  44. Legrand M, Darmon M, Joannidis M, Payen D (2013) Management of renal replacement therapy in ICU patients: an international survey. Intensive Care Med 39(1):101–108

    Article  PubMed  Google Scholar 

  45. Fiaccadori E, Pistolesi V, Mariano F et al (2015) 2015) Regional citrate anticoagulation for renal replacement therapies in patients with acute kidney injury: a position statement of the Work Group "Renal Replacement Therapies in Critically Ill Patients" of the Italian Society of Nephrology. J Nephrol 28(2):151–164

    Article  CAS  PubMed  Google Scholar 

  46. Tolwani A, Wille KM (2012) Advances in continuous renal replacement therapy: citrate anticoagulation update. Blood Purif 34(2):88–93

    Article  CAS  PubMed  Google Scholar 

  47. Locatelli F, La Milia V, Violo L, Del Vecchio L, Di Filippo S (2015) Optimizing haemodialysate composition. Clin Kidney J 8(5):580–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kyriazis J, Kalogeropoulou K, Bilirakis L et al (2004) Dialysate magnesium level and blood pressure. Kidney Int 66(3):1221–1231

    Article  CAS  PubMed  Google Scholar 

  49. Navarro-Gonzalez JF, Mora-Fernandez C, Garcia-Perez J (2009) Clinical implications of disordered magnesium homeostasis in chronic renal failure and dialysis. Semin Dial 22(1):37–44

    Article  PubMed  Google Scholar 

  50. Godaly G, Carlsson O, Broman M (2016) Phoxilium(®) reduces hypophosphataemia and magnesium supplementation during continuous renal replacement therapy. Clin Kidney J 9(2):205–210

    Article  CAS  PubMed  Google Scholar 

  51. Janssen M, Huijgens P, Bouman A, Oe P, Van der Meulen J (1994) Citrate anticoagulation and divalent cations in hemodialysis. Blood Purif 12(6):308–316

    Article  CAS  PubMed  Google Scholar 

  52. Zakharchenko M, Los F, Brodska H, Balik M (2016) The effects of high-level magnesium dialysis/substitution fluid on magnesium homeostasis under regional citrate anticoagulation in critically ill. PLoS ONE 11(7):e0158179

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  53. Jeffrey YH, Hoi-Ping S, Kit Hung AL, Chung-Ling L, Wing-Wa Y, King-Yiu L (2017) Experiences with continuous venovenous hemofiltration using 18 mmol/L predilution citrate anticoagulation and a phosphate containing replacement solution. Indian J Crit Care Med 21(1):11–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Balik M, Zakharchenko M, Leden P et al (2014) The effects of a novel calcium-free lactate buffered dialysis and substitution fluid for regional citrate anticoagulation–prospective feasibility study. Blood Purif 38(3–4):263–272

    Article  CAS  PubMed  Google Scholar 

  55. Fiaccadori E, Regolisti G, Cademartiri C et al (2013) Efficacy and safety of a citrate-based protocol for sustained low-efficiency dialysis in AKI using standard dialysis equipment. Clin J Am Soc Nephrol 8(10):1670–1678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Agus MS, Agus ZS (2001) Cardiovascular actions of magnesium. Crit Care Clin 17(1):175–186

    Article  CAS  PubMed  Google Scholar 

  57. João Matias P, Azevedo A, Laranjinha I et al (2014) Lower serum magnesium is associated with cardiovascular risk factors and mortality in haemodialysis patients. Blood Purif 38(3–4):244–252

    Article  PubMed  CAS  Google Scholar 

  58. Ford ES, Li C, McGuire LC, Mokdad AH, Liu S (2007) Intake of dietary magnesium and the prevalence of the metabolic syndrome among U.S. adults. Obesity (Silver Spring) 15(5):1139–1146

    Article  CAS  Google Scholar 

  59. Mohammed S, Goodacre S (2007) Intravenous and nebulised magnesium sulphate for acute asthma: systematic review and meta-analysis. Emerg Med J 24(12):823–830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Alves SC, Tomasi CD, Constantino L et al (2013) Hypomagnesemia as a risk factor for the non-recovery of the renal function in critically ill patients with acute kidney injury. Nephrol Dial Transplant 28(4):910–916

    Article  PubMed  Google Scholar 

  61. Huang CL, Kuo E (2007) Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol 18(10):2649–2652

    Article  PubMed  CAS  Google Scholar 

  62. Rossi GM, Regolisti G, Peyronel F, Fiaccadori E (2020) Recent insights into sodium and potassium handling by the aldosterone-sensitive distal nephron: a review of the relevant physiology. J Nephrol. https://doi.org/10.1007/s40620-019-00684-1

    Article  PubMed  PubMed Central  Google Scholar 

  63. Rossi GM, Regolisti G, Peyronel F, Fiaccadori E (2020) Recent insights into sodium and potassium handling by the aldosterone-sensitive distal nephron: implications on pathophysiology and drug discovery. J Nephrol. https://doi.org/10.1007/s40620-020-00700-9

    Article  PubMed  PubMed Central  Google Scholar 

  64. Martin KJ, Gonzalez EA, Slatopolsky E (2009) Clinical consequences and management of hypomagnesemia. J Am Soc Nephrol 20(11):2291–2295

    Article  CAS  PubMed  Google Scholar 

  65. Ayuk J, Gittoes NJL (2014) Treatment of hypomagnesemia. Am J Kidney Dis 63(4):691–695

    Article  CAS  PubMed  Google Scholar 

  66. Maynar Moliner J, Honore PM, Sánchez-Izquierdo Riera JA, Herrera Gutiérrez ME, Spapen HD (2012) Handling continuous renal replacement therapy-related adverse effects in intensive care unit patients: the dialytrauma concept. Blood Purif 34(2):177–185

    Article  CAS  PubMed  Google Scholar 

  67. Chua HR, Baldwin I, Ho L, Collins A, Allsep H, Bellomo R (2012) Biochemical effects of phosphate-containing replacement fluid for continuous venovenous hemofiltration. Blood Purif 34(3–4):306–312

    Article  CAS  PubMed  Google Scholar 

  68. Pistolesi V, Zeppilli L, Polistena F et al (2017) Preventing continuous renal replacement therapy-induced hypophosphatemia: an extended clinical experience with a phosphate-containing solution in the setting of regional citrate anticoagulation. Blood Purif 44(1):8–15

    Article  CAS  PubMed  Google Scholar 

  69. Pistolesi V, Zeppilli L, Fiaccadori E, Regolisti G, Tritapepe L, Morabito S (2019) Hypophosphatemia in critically ill patients with acute kidney injury on renal replacement therapies. J Nephrol 32(6):895–908

    Article  CAS  PubMed  Google Scholar 

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  1. Dipartimento di Medicina e Chirurgia, UO Nefrologia, Unità Operativa di Nefrologia, Azienda Ospedaliero-Universitaria Parma, Università̀ di Parma, Via Gramsci 14, 43100, Parma, Italy

    Francesca Di Mario, Giuseppe Regolisti, Paolo Greco, Caterina Maccari, Eleonora Superchi & Enrico Fiaccadori

  2. UOSD Dialisi, Azienda Ospedaliero-Universitaria Policlinico Umberto I, “Sapienza” Università̀ di Roma, Rome, Italy

    Santo Morabito & Valentina Pistolesi

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  1. Francesca Di Mario
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  2. Giuseppe Regolisti
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Di Mario, F., Regolisti, G., Greco, P. et al. Prevention of hypomagnesemia in critically ill patients with acute kidney injury on continuous kidney replacement therapy: the role of early supplementation and close monitoring. J Nephrol 34, 1271–1279 (2021). https://doi.org/10.1007/s40620-020-00864-4

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