Ann Lab Med.  2024 Jan;44(1):21-28. 10.3343/alm.2024.44.1.21.

Ionized Magnesium Correlates With Total Blood Magnesium in Pediatric Patients Following Kidney Transplant

• Hasson DC
• Mohan S
• Rose JE
• Merrill KA
• Goldstein SL
• Benoit SW
• Varnell Jr. CD

• KMID: 2550212
• DOI: http://doi.org/10.3343/alm.2024.44.1.21

Abstract

Background
Abnormal serum magnesium (Mg) concentrations are common and associated with worse mortality in kidney-transplant recipients. Many kidney and transplant-related factors affect Mg homeostasis. The concentration of the active form, ionized Mg (iMg), is not measured clinically, and total Mg (tMg) and iMg correlations have conflicted. We hypothesized that iMg and tMg concentrations show poor categorical agreement (i.e., low, normal, and high) in kidney-transplant recipients but that ionized calcium (iCa) correlates with iMg.
Methods
We retrospectively evaluated hypomagnesemia in kidney-transplant recipients over a 2-yr period. We prospectively collected blood at 0–28 days post-transplant to measure correlations between iMg and iCa/tMg. iMg and iCa concentrations in the reference ranges of 0.44–0.65 and 1.0–1.3 mmol/L, respectively, were considered normal. Fisher’s exact test and unweighted kappa statistics revealed category agreements. Pearson’s correlation coefficients and linear regression measured correlations.
Results
Among 58 retrospective kidney-transplant recipients, 54 (93%) had tMg < 0.66 mmol/L, 28/58 (48%) received Mg supplementation, and 20/28 (71%) had tacrolimus dose adjustments during supplementation. In 13 prospective transplant recipients (N = 43 samples), iMg and tMg showed strong category agreement (P = 0.0003) and correlation (r = 0.71, P < 0.001), whereas iMg and iCa did not (P = 0.7; r = –0.25, P = 0.103, respectively).
Conclusions
tMg and iMg exhibited strong correlation following kidney transplantation. However, iCa may not be an accurate surrogate for iMg. Determining the effect of Mg supplementation and the Mg concentration where supplementation is clinically necessary are important next steps.

Keyword

Calcium; Electrolyte; Ionized; Kidney disease; Kidney transplantation; Magnesium

Figure

• 

  Fig. 1 Correlations between iMg and tMg or iCa in prospective kidney transplant recipients. (A) Pearson’s correlation coefficients and simple linear regression analysis were used to assess the relationship between iMg and tMg (Pearson’s r=0.707). The dashed line represents the linear regression equation (P<0.001). (B) Correlation between iMg and iCa, with the dashed line representing the linear regression equation (Pearson’s r=–0.252, P=0.103). For conversion from mmol/L to mg/dL, multiplication factors of 2.43 and 4 are used for Mg and Ca, respectively. Abbreviations: iMg, ionized magnesium; tMg, total magnesium; iCa, ionized calcium.

Reference

1. Broner CW, Stidham GL, Westenkirchner DF, Tolley EA. 1990; Hypermagnesemia and hypocalcemia as predictors of high mortality in critically ill pediatric patients. Crit Care Med. 18:921–8. DOI: 10.1097/00003246-199009000-00004. PMID: 2394115.

2. Rubeiz GJ, Thill-Baharozian M, Hardie D, Carlson RW. 1993; Association of hypomagnesemia and mortality in acutely ill medical patients. Crit Care Med. 21:203–9. DOI: 10.1097/00003246-199302000-00010. PMID: 8428470.

3. Soliman HM, Mercan D, Lobo SSM, Mélot C, Vincent JL. 2003; Development of ionized hypomagnesemia is associated with higher mortality rates. Crit Care Med. 31:1082–7. DOI: 10.1097/01.CCM.0000060867.17556.A0. PMID: 12682476.

4. Escuela MP, Guerra M, Añón JM, Martínez-Vizcaíno V, Zapatero MD, García-Jalón A, et al. 2005; Total and ionized serum magnesium in critically ill patients. Intensive Care Med. 31:151–6. DOI: 10.1007/s00134-004-2508-x. PMID: 15605229.

5. Tong GM, Rude RK. 2005; Magnesium deficiency in critical illness. J Intensive Care Med. 20:3–17. DOI: 10.1177/0885066604271539. PMID: 15665255.

6. Johansson M, Whiss PA. 2007; Weak relationship between ionized and total magnesium in serum of patients requiring magnesium status. Biol Trace Elem Res. 115:13–21. DOI: 10.1385/BTER:115:1:13. PMID: 17406070.

7. Koch SM, Warters RD, Mehlhorn U. 2002; The simultaneous measurement of ionized and total calcium and ionized and total magnesium in intensive care unit patients. J Crit Care. 17:203–5. DOI: 10.1053/jcrc.2002.35813. PMID: 12297997.

8. Yeh DD, Chokengarmwong N, Chang Y, Yu L, Arsenault C, Rudolf J, et al. 2017; Total and ionized magnesium testing in the surgical intensive care unit - opportunities for improved laboratory and pharmacy utilization. J Crit Care. 42:147–51. DOI: 10.1016/j.jcrc.2017.07.026. PMID: 28732315.

9. Fiser RT, Torres A Jr, Butch AW, Valentine JL. 1998; Ionized magnesium concentrations in critically ill children. Crit Care Med. 26:2048–52. DOI: 10.1097/00003246-199812000-00039. PMID: 9875919.

10. Spiegel DM. 2011; Magnesium in chronic kidney disease: unanswered questions. Blood Purif. 31:172–6. DOI: 10.1159/000321837. PMID: 21228586.

11. Allegra A, Corica F, Ientile R, Corsonello A, Sparacino V, Accettola F, et al. 1998; Plasma (total and ionized), erythrocyte and platelet magnesium levels in renal transplant recipients during cyclosporine and/or azathioprine treatment. Magnes Res. 11:11–8. DOI: 10.1007/978-94-009-0057-8_62.

12. Navaneethan SD, Sankarasubbaiyan S, Gross MD, Jeevanantham V, Monk RD. 2006; Tacrolimus-associated hypomagnesemia in renal transplant recipients. Transplant Proc. 38:1320–2. DOI: 10.1016/j.transproceed.2006.02.077. PMID: 16797291.

13. Filler G. 2007; Calcineurin inhibitors in pediatric renal transplant recipients. Paediatr Drugs. 9:165–74. DOI: 10.2165/00148581-200709030-00005. PMID: 17523697.

14. Mazzola BL, Vannini SDP, Truttmann AC, von Vigier RO, Wermuth B, Ferrari P, et al. 2003; Long-term calcineurin inhibition and magnesium balance after renal transplantation. Transpl Int. 16:76–81. DOI: 10.1111/j.1432-2277.2003.tb00267.x. PMID: 12595968.

15. Glasdam SM, Glasdam S, Peters GH. 2016; The importance of magnesium in the human body: a systematic literature review. Adv Clin Chem. 73:169–93. DOI: 10.1016/bs.acc.2015.10.002. PMID: 26975973.

16. Greenway DC, Hindmarsh JT, Wang J, Khodadeen JA, Hébert PC. 1996; Reference interval for whole blood ionized magnesium in a healthy population and the stability of ionized magnesium under varied laboratory conditions. Clin Biochem. 29:515–20. DOI: 10.1016/S0009-9120(96)00091-4. PMID: 8939398.

17. Hristova EN, Cecco S, Niemela JE, Rehak NN, Elin RJ. 1995; Analyzer-dependent differences in results for ionized calcium, ionized magnesium, sodium, and pH. Clin Chem. 41:1649–53. DOI: 10.1093/clinchem/41.11.1649. PMID: 7586557.

18. Hoshino K, Ogawa K, Kitazawa R, Nakamura Y, Uehara R. 1998; Ionized magnesium level in whole blood of healthy Japanese children. Acta Paediatr Jpn. 40:116–21. DOI: 10.1111/j.1442-200X.1998.tb01894.x. PMID: 9581300.

19. Dent A, Selvaratnam R. Measuring magnesium - physiological, clinical and analytical perspectives. Clin Biochem. 2022; 105-106:1–15. DOI: 10.1016/j.clinbiochem.2022.04.001. PMID: 35381264.

20. Vannini SD, Mazzola BL, Rodoni L, Truttmann AC, Wermuth B, Bianchetti MG, et al. 1999; Permanently reduced plasma ionized magnesium among renal transplant recipients on cyclosporine. Transpl Int. 12:244–9. DOI: 10.1111/j.1432-2277.1999.tb01208.x. PMID: 10460868.

21. Markell MS, Altura BT, Barbour RL, Altura BM. 1993; Ionized and total magnesium levels in cyclosporin-treated renal transplant recipients: relationship with cholesterol and cyclosporin levels. Clin Sci (Lond). 85:315–8. DOI: 10.1042/cs0850315. PMID: 8403804.

22. Zhan J, Wallace TC, Butts SJ, Cao S, Ansu V, Spence LA, et al. 2020; Circulating ionized magnesium as a measure of supplement bioavailability: results from a pilot study for randomized clinical trial. Nutrients. 12:1245. DOI: 10.3390/nu12051245. PMID: 32353962. PMCID: PMC7281967.

23. Ivanovic ND, Radosavljevic B, Zekovic M, Korcok D, Ignjatovic S, Djordjevic B, et al. 2022; Effects of short-term magnesium supplementation on ionized, total magnesium and other relevant electrolytes levels. Biometals. 35:267–83. DOI: 10.1007/s10534-022-00363-y. PMID: 35041150.

24. Zehtabchi S, Sinert R, Rinnert S, Chang B, Heinis C, Altura RA, et al. 2004; Serum ionized magnesium levels and ionized calcium-to-magnesium ratios in adult patients with sickle cell anemia. Am J Hematol. 77:215–22. DOI: 10.1002/ajh.20187. PMID: 15495259.

25. Hutten TJA, Sikma MA, Stokwielder RH, Wesseling M, Hoefer IE, Tiel Groenestege WM. 2021; Ionized and not total magnesium as a discriminating biomarker for hypomagnesaemia in continuous venovenous haemofiltration patients. Nephrol Dial Transplant. 36:742–3. DOI: 10.1093/ndt/gfaa330. PMID: 33561265.

26. Wang S, McDonnell EH, Sedor FA, Toffaletti JG. 2002; pH effects on measurements of ionized calcium and ionized magnesium in blood. Arch Pathol Lab Med. 126:947–50. DOI: 10.5858/2002-126-0947-PEOMOI. PMID: 12171493.

27. Bouillon-Minois JB, Khaled L, Vitte F, Miraillet L, Eschalier R, Jabaudon M, et al. 2023; Ionized magnesium: interpretation and interest in atrial fibrillation. Nutrients. 15:236. DOI: 10.3390/nu15010236. PMID: 36615893. PMCID: PMC9823795.