Magnesium supplementation may not be protective against carboplatin-induced nephrotoxicity but may be beneficial for children suffering malignancies: A randomized clinical trial


1 Department of Pediatrics, Amir Kabir Hospital, Arak University of Medical Sciences, Arak, Iran

2 Department of Basic and Laboratory Sciences, Khomein University of Medical Sciences, Khomein, Iran

3 Department of Pediatrics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

4 Department of Biochemistry and Hematology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran

5 Clinical Research Development Center, Aliasghar Hospital, Iran University of Medical Sciences, Tehran, Iran


Background: Magnesium oxide may be effective in renal insufficiency prevention after carboplatin therapy. We have evaluated magnesium oxide impression on the serum creatinine (Cr) and blood urea nitrogen (BUN) levels plus glomerular filtration rate (GFR) in cancerous children.
Materials and Methods: A group of children with different cancers (n = 18) was treated with 250 mg/day magnesium oxide supplementation (MOS) and compared with a matched placebo-treated group (n = 18). After 2 weeks, carboplatin chemotherapy started. We compared serum Cr, BUN, and GFR values before and 3 and 7 days post intervention.
Results: Serum Cr and BUN were increased significantly 3 and 7 days after intervention in both the groups. Serum Cr and BUN were not statistically different between the MOS and placebo groups before the intervention and 3 or 7 days after carboplatin administration (P > 0.05). Three days after the intervention, the GFR reduced from 101.38 ± 14.67 to 90.11 ± 10.52 mL/min/1.73 m2 in the MOS group. Furthermore, in the placebo group, 3 days after the intervention, the GFR was reduced from 97.5 ± 9.71 to 92.33 ± 10.61 mL/min/1.73 m2. Further, in the MOS group, after 7 days of the intervention, the GFR was reduced to 84.11 ± 12.47 mL/min/1.73 m2. In the placebo group, after 7 days of the intervention, the GFR was diminished to 85.38 ± 10.66 mL/min/1.73 m2 (P = 0.371).
Conclusion: The current study suggests that magnesium supplementation does not prevent carboplatin-induced nephrotoxicity in children with malignancies. Anyway, we propose magnesium oxide supplementation for this group of pediatrics because magnesium is an essential element for cell and tissue growth, maintenance, and metabolism.


Celakil ME, Berrak SG. Evaluation of the awareness of childhood cancers by general practitioners, family physicians and pediatricians. Marmara Med J 2020;33:119-27.  Back to cited text no. 1
Gibson F, Pearce S, Fern L, Martins A, Kelly D. Improving the identification of cancer in young people: A scoping review. Expert Rev Qual Life Cancer Care 2017;2:87-101.  Back to cited text no. 2
Islami F, Ward EM, Sung H, Cronin KA, Tangka FK, Sherman RL, et al. Annual report to the nation on the status of cancer, part 1: national cancer statistics. J Natl Cancer Inst 2021;113:1648-69.  Back to cited text no. 3
NIH. National Cancer Institute. Childhood Cancers; 2020. Available from: [Last updated on 2021 Apr 12; Last cited on 2021 Oct 20].  Back to cited text no. 4
Li XY, Li JQ, Luo XQ, Wu XD, Sun X, Xu HG, et al. Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia-a multi-centric clinical study of GD-2008-ALL protocol. BMC Cancer 2021;21:1-11.  Back to cited text no. 5
Voulgaridou A, Athanasiadou KI, Athanasiadou E, Roilides E, Papakonstantinou E. Pulmonary infectious complications in children with hematologic malignancies and chemotherapy-induced neutropenia. Diseases 2020;8:E32.  Back to cited text no. 6
Kooijmans EC, Bökenkamp A, Tjahjadi NS, Tettero JM, van Dulmen-den Broeder E, van der Pal HJ, et al. Early and late adverse renal effects after potentially nephrotoxic treatment for childhood cancer. Cochrane Database Syst Rev 2019;3:CD008944.  Back to cited text no. 7
Barton CD, Pizer B, Jones C, Oni L, Pirmohamed M, Hawcutt DB. Identifying cisplatin-induced kidney damage in paediatric oncology patients. Pediatr Nephrol 2018;33:1467-74.  Back to cited text no. 8
Oun R, Moussa YE, Wheate NJ. The side effects of platinum-based chemotherapy drugs: A review for chemists. Dalton Trans 2018;47:6645-53.  Back to cited text no. 9
Price P, Sikora K. Treatment of Cancer. Boca Raton, Florida, United States: CRC Press; 2020.  Back to cited text no. 10
Udaka YT, Packer RJ. Pediatric brain tumors. Neurol Clin 2018;36:533-56.  Back to cited text no. 11
Raitio A, Rice MJ, Mullassery D, Losty PD. Stage 4S neuroblastoma: What are the outcomes? A systematic review of published studies. Eur J Pediatr Surg 2021;31:385-9.  Back to cited text no. 12
Vaarwerk B, van der Lee JH, Breunis WB, Orbach D, Chisholm JC, Cozic N, et al. Prognostic relevance of early radiologic response to induction chemotherapy in pediatric rhabdomyosarcoma: A report from the International Society of Pediatric Oncology Malignant Mesenchymal Tumor 95 study. Cancer 2018;124:1016-24.  Back to cited text no. 13
Oostveen RM, Pritchard-Jones K. Pharmacotherapeutic management of wilms tumor: An update. Paediatr Drugs 2019;21:1-13.  Back to cited text no. 14
Volarevic V, Djokovic B, Jankovic MG, Harrell CR, Fellabaum C, Djonov V, et al. Molecular mechanisms of cisplatin-induced nephrotoxicity: A balance on the knife edge between renoprotection and tumor toxicity. J Biomed Sci 2019;26:25.  Back to cited text no. 15
Manohar S, Leung N. Cisplatin nephrotoxicity: A review of the literature. J Nephrol 2018;31:15-25.  Back to cited text no. 16
Wallace TC. Combating COVID-19 and building immune resilience: A potential role for magnesium nutrition? J Am Coll Nutr 2020;39:685-93.  Back to cited text no. 17
Xue W, You J, Su Y, Wang Q. The effect of magnesium deficiency on neurological disorders: A narrative review article. Iran J Public Health 2019;48:379-87.  Back to cited text no. 18
Pollock N, Chakraverty R, Taylor I, Killer SC. An 8-year analysis of magnesium status in elite international track & field athletes. J Am Coll Nutr 2020;39:443-9.  Back to cited text no. 19
Wang J, Um P, Dickerman BA, Liu J. Zinc, magnesium, selenium and depression: A review of the evidence, potential mechanisms and implications. Nutrients 2018;10:584.  Back to cited text no. 20
Feng J, Wang H, Jing Z, Wang Y, Cheng Y, Wang W, et al. Role of magnesium in type 2 diabetes mellitus. Biol Trace Elem Res 2020;196:74-85.  Back to cited text no. 21
Schutten JC, Joosten MM, de Borst MH, Bakker SJ. Magnesium and blood pressure: A physiology-based approach. Adv Chronic Kidney Dis 2018;25:244-50.  Back to cited text no. 22
Yan X, Sheng X, Chi Z, Si L, Cui C, Kong Y, et al. Randomized Phase II study of bevacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated advanced mucosal melanoma. J Clin Oncol 2021;39:881-9.  Back to cited text no. 23
Gaughran G, Qayyum K, Smyth L, Davis A. Carboplatin and hypomagnesemia: Is it really a problem? Asia Pac J Clin Oncol 2021;17:478-85.  Back to cited text no. 24
Saito Y, Kobayashi M, Yamada T, Kasashi K, Honma R, Takeuchi S, et al. Premedication with intravenous magnesium has a protective effect against cisplatin-induced nephrotoxicity. Support Care Cancer 2017;25:481-7.  Back to cited text no. 25
Ikemura K, Oshima K, Enokiya T, Okamoto A, Oda H, Mizuno T, et al. Co-administration of proton pump inhibitors ameliorates nephrotoxicity in patients receiving chemotherapy with cisplatin and fluorouracil: A retrospective cohort study. Cancer Chemother Pharmacol 2017;79:943-9.  Back to cited text no. 26
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-12.  Back to cited text no. 27
Matsui M, Saito Y, Yamaoka S, Yokokawa Y, Morikawa Y, Makimoto A, et al. Kidney-protective effect of magnesium supplementation in cisplatin-containing chemotherapy for pediatric cancer: A retrospective study. J Pediatr Hematol Oncol 2018;40:379-81.  Back to cited text no. 28
Kimura T, Ozawa T, Hanai N, Hirakawa H, Suzuki H, Hosoi H, et al. Renal protective effect of a hydration supplemented with magnesium in patients receiving cisplatin for head and neck cancer. J Otolaryngol Head Neck Surg 2018;47:10.  Back to cited text no. 29
Yamaguchi T, Uozu S, Isogai S, Hayashi M, Goto Y, Nakanishi T, et al. Short hydration regimen with magnesium supplementation prevents cisplatin-induced nephrotoxicity in lung cancer: A retrospective analysis. Support Care Cancer 2017;25:1215-20.  Back to cited text no. 30
Skinner R, Parry A, Price L, Cole M, Craft AW, Pearson AD. Persistent nephrotoxicity during 10-year follow-up after cisplatin or carboplatin treatment in childhood: Relevance of age and dose as risk factors. Eur J Cancer 2009;45:3213-9.  Back to cited text no. 31
Stöhr W, Paulides M, Bielack S, Jürgens H, Koscielniak E, Rossi R, et al. Nephrotoxicity of cisplatin and carboplatin in sarcoma patients: A report from the late effects surveillance system. Pediatr Blood Cancer 2007;48:140-7.  Back to cited text no. 32
Shahbazian H, Absalan A, Jalali MT, Mastipour F, Kaydani GA, Zayeri ZD. Comparison of zinc, copper, selenium, magnesium, aluminium and lead blood concentrations in end-stage renal disease patients and healthy volunteers in Ahvaz, southwest of Iran. Russ Open Med J 2018;7:1-4.  Back to cited text no. 33