Skip to main content

Advertisement

SpringerLink
Log in

Preventive effect of 20 mEq and 8 mEq magnesium supplementation on cisplatin-induced nephrotoxicity: a propensity score–matched analysis

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Purpose

The protective effect of magnesium (Mg) supplementation against cisplatin (CDDP)-induced nephrotoxicity has been widely described; however, the optimal dose of Mg supplementation is unclear. The aim of this study was to investigate whether 20 mEq of Mg supplementation is more effective than 8 mEq Mg in preventing CDDP-induced nephrotoxicity, as well as the associated risk factors, in cancer patients treated with CDDP-based chemotherapy.

Methods

Pooled data of 272 patients receiving 20 mEq or 8 mEq Mg supplementation to CDDP-based chemotherapy from a multicenter, retrospective, observational study were compared using propensity score matching. Separate multivariate logistic regression analyses were used to identify the risk factors for renal failure induced by each treatment dose.

Results

There was no significant difference in the incidence of nephrotoxicity between the 8 mEq and 20 mEq groups (P = 0.926). There was also no significant difference in the severity of nephrotoxicity, elevated serum creatinine levels, and decreased estimated creatinine clearance levels between the two groups. Cardiac disease and albumin levels were identified as independent risk factors for CDDP-induced nephrotoxicity.

Conclusion

We did not find an advantage of 20 mEq over 8 mEq Mg supplementation in terms of a preventive effect against CDDP-induced nephrotoxicity. The optimal dose of Mg supplementation for the prevention of CDDP-induced nephrotoxicity remains unknown, and further studies are warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

Data supporting the findings of this study are available from the corresponding author on reasonable request. However, restrictions apply to the availability of these data, which were used under a license for the current study and are, thus, not publicly available.

Code availability

Not applicable.

References

  1. Hartmann JT, Lipp HP (2003) Toxicity of platinum compounds. Expert Opin Pharmacother 4:889–901. https://doi.org/10.1517/14656566.4.6.889

    Article  CAS  PubMed  Google Scholar 

  2. Sastry J, Kellie SJ (2005) Severe neurotoxicity, ototoxicity and nephrotoxicity following high-dose cisplatin and amifostine. Pediatr Hematol Oncol 22:441–445. https://doi.org/10.1080/08880010590964381

    Article  CAS  PubMed  Google Scholar 

  3. Ries F, Klastersky J (1986) Nephrotoxicity induced by cancer chemotherapy with special emphasis on cisplatin toxicity. Am J Kidney Dis 8:368–379. https://doi.org/10.1016/s0272-6386(86)80112-3

    Article  CAS  PubMed  Google Scholar 

  4. Dobyan DC, Levi J, Jacobs C, Kosek J, Weiner MW (1980) Mechanism of cis-platinum nephrotoxicity: II. Morphologic observations J Pharmacol Exp Ther 213:551–556

    CAS  PubMed  Google Scholar 

  5. Pinzani V, Bressolle F, Haug IJ, Galtier M, Blayac JP, Balmès P (1994) Cisplatin-induced renal toxicity and toxicity-modulating strategies: a review. Cancer Chemother Pharmacol 35:1–9. https://doi.org/10.1007/BF00686277

    Article  CAS  PubMed  Google Scholar 

  6. Cornelison TL, Reed E (1993) Nephrotoxicity and hydration management for cisplatin, carboplatin, and ormaplatin. Gynecol Oncol 50:147–158. https://doi.org/10.1006/gyno.1993.1184

    Article  CAS  PubMed  Google Scholar 

  7. Sobrero A, Guglielmi A, Aschele C, Rosso R (1990) Current strategies to reduce cisplatin toxicity. J Chemother 2:3–7. https://doi.org/10.1080/1120009x.1990.11738971

    Article  CAS  PubMed  Google Scholar 

  8. Finley RS, Fortner CL, Grove WR (1985) Cisplatin nephrotoxicity: a summary of preventative interventions. Drug Intell Clin Pharm 19:362–367. https://doi.org/10.1177/106002808501900505

    Article  CAS  PubMed  Google Scholar 

  9. Lajer H, Daugaard G (1999) Cisplatin and hypomagnesemia. Cancer Treat Rev 25:47–58. https://doi.org/10.1053/ctrv.1999.0097

    Article  CAS  PubMed  Google Scholar 

  10. Vickers AEM, Rose K, Fisher R, Saulnier M, Sahota P, Bentley P (2004) Kidney slices of human and rat to characterize cisplatin-induced injury on cellular pathways and morphology. Toxicol Pathol 32:577–590. https://doi.org/10.1080/01926230490508821

    Article  CAS  PubMed  Google Scholar 

  11. Alves SC, Tomasi CD, Constantino L, Giombelli V, Candal R, Bristot Mde L, Topanotti MF, Burdmann EA, Dal-Pizzol F, Fraga CM, Ritter C (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 28:910–916. https://doi.org/10.1093/ndt/gfs268

    Article  PubMed  Google Scholar 

  12. Bodnar L, Wcislo G, Gasowska-Bodnar A, Synowiec A, Szarlej-Wcisło K, Szczylik C (2008) Renal protection with magnesium subcarbonate and magnesium sulphate in patients with epithelial ovarian cancer after cisplatin and paclitaxel chemotherapy: a randomised phase II study. Eur J Cancer 44:2608–2614. https://doi.org/10.1016/j.ejca.2008.08.005

    Article  CAS  PubMed  Google Scholar 

  13. Willox JC, McAllister EJ, Sangster G, Kaye SB (1986) Effects of magnesium supplementation in testicular cancer patients receiving cis-platin: a randomised trial. Br J Cancer 54:19–23. https://doi.org/10.1038/bjc.1986.147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Martin M, Diaz-Rubio E, Casado A, López Vega JM, Sastre J, Almenarez J (1992) Intravenous and oral magnesium supplementations in the prophylaxis of cisplatin-induced hypomagnesemia. Results of a controlled trial. Am J Clin Oncol 15:348–351. https://doi.org/10.1097/00000421-199208000-00016

    Article  CAS  PubMed  Google Scholar 

  15. Yoshida T, Niho S, Toda M, Goto K, Yoh K, Umemura S, Matsumoto S, Ohmatsu H, Ohe Y (2014) Protective effect of magnesium preloading on cisplatin-induced nephrotoxicity: a retrospective study. Jpn J Clin Oncol 44:346–354. https://doi.org/10.1093/jjco/hyu004

    Article  PubMed  Google Scholar 

  16. Hotta K, Takigawa N, Hisamoto-Sato A, Ichihara E, Kudo K, Uchida K, Yanase-Nakamura K, Tanaka H, Kato Y, Tabata M, Tanimoto M, Kiura K (2013) Reappraisal of short-term low-volume hydration in cisplatin-based chemotherapy: results of a prospective feasibility study in advanced lung cancer in the Okayama lung cancer study group Trial 1002. Jpn J Clin Oncol 43:1115–1123. https://doi.org/10.1093/jjco/hyt128

    Article  PubMed  Google Scholar 

  17. Horinouchi H, Kubota K, Itani H, Taniyama TK, Nakamichi S, Wakui H, Kanda S, Nokihara H, Yamamoto N, Sekine I, Tamura T (2013) Short hydration in chemotherapy containing cisplatin (>=75 mg/m2) for patients with lung cancer: a prospective study. Jpn J Clin Oncol 43:1105–1109. https://doi.org/10.1093/jjco/hyt122

    Article  PubMed  Google Scholar 

  18. Kidera Y, Kawakami H, Sakiyama T, Okamoto K, Tanaka K, Takeda M, Kaneda H, Nishina S-I, Tsurutani J, Fujiwara K, Nomura M, Yamazoe Y, Chiba Y, Nishida S, Tamura T, Nakagawa K (2014) Risk factors for cisplatin-induced nephrotoxicity and potential of magnesium supplementation for renal protection. PLoS ONE 9:e101902. https://doi.org/10.1371/journal.pone.0101902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hase T, Miyazaki M, Ichikawa K, Yogo N, Ozawa N, Hatta T, Ando M, Sato M, Kondo M, Yamada K, Hasegawa Y (2020) Short hydration with 20 mEq of magnesium supplementation for lung cancer patients receiving cisplatin-based chemotherapy: a prospective study. Int J Clin Oncol 25:1928–1935. https://doi.org/10.1007/s10147-020-01755-1

    Article  CAS  PubMed  Google Scholar 

  20. Miyoshi T, Uoi M, Omura F, Tsumagari K, Maesaki S, Yokota C (2021) Risk factors for cisplatin-induced nephrotoxicity: a multicenter retrospective study. Oncology 99:105–113. https://doi.org/10.1159/00051038421

    Article  CAS  PubMed  Google Scholar 

  21. Haim N, Oman SD, Galai N, Burde B, Nathan S, Catane R (1993) Estimation of creatinine clearance without 24-hour urine collection—a useful guide during cisplatin therapy. Acta oncol 32:409–412. https://doi.org/10.3109/02841869309093618

    Article  CAS  PubMed  Google Scholar 

  22. Motwani SS, McMahon GM, Humphreys BD, Partridge AH, Waikar SS, Curhan GC (2018) Development and validation of a risk prediction model for acute kidney injury after the first course of cisplatin. J Clin Oncol 36:682–688. https://doi.org/10.1200/JCO.2017.75.7161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mizuno T, Ishikawa K, Sato W, Koike T, Kushida M, Miyagawa Y, Yamada K, Hirata S, Imai E, Noda Y (2013) The risk factors of severe acute kidney injury induced by cisplatin. Oncology 85:364–369. https://doi.org/10.1159/000356587

    Article  CAS  PubMed  Google Scholar 

  24. Saito Y, Kobayashi M, Yamada T, Kasashi K, Honma R, Takeuchi S, Shimizu Y, Kinoshita I, Dosaka-Akita H, Iseki K (2017) Premedication with intravenous magnesium has a protective effect against cisplatin-induced nephrotoxicity. Support Care Cancer 25:481–487. https://doi.org/10.1007/s00520-016-3426-5

    Article  PubMed  Google Scholar 

  25. Tong GM, Rude RK (2005) Magnesium deficiency in critical illness. J Intensive Care Med 20:3–17. https://doi.org/10.1177/0885066604271539

    Article  PubMed  Google Scholar 

  26. Horiuchi M, Inuyama Y, Kohno N, Mashino S, Fujii M (1982) Pharmacokinetics of cis-dichlorodiammineplatinum (II). Gan To Kagaku Ryoho 9:632–637

    CAS  PubMed  Google Scholar 

  27. Nagai N, Kinoshita M, Ogata H, Tsujino D, Wada Y, Someya K, Ohno T, Masuhara K, Tanaka Y, Kato K, Nagai H, Yokoyama A, Kurita Y (1996) Relationship between pharmacokinetics of unchanged cisplatin and nephrotoxicity after intravenous infusions of cisplatin to cancer patients. Cancer Chemother Pharmacol 39:131–137. https://doi.org/10.1007/s002800050548

    Article  CAS  PubMed  Google Scholar 

  28. Nagai N, Ogata H (1997) Quantitative relationship between pharmacokinetics of unchanged cisplatin and nephrotoxicity in rats: importance of area under the concentration-time curve (AUC) as the major toxicodynamic determinant in vivo. Cancer Chemother Pharmacol 40:11–18. https://doi.org/10.1007/s002800050618

    Article  CAS  PubMed  Google Scholar 

  29. Teramachi H, Hatakeyama H, Matsushita R, Imai Y, Miyamoto KI, Tsuji A (2002) Evaluation of predictability for vancomycin dosage regimens by the Bayesian method with Japanese population pharmacokinetic parameters. Biol Pharm Bull 25:1333–1338. https://doi.org/10.1248/bpb.25.1333

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all of the participants of the study and their families.

Author information

Authors and Affiliations

  1. Department of Pharmacy, National Hospital Organization Kyushu Medical Center, 1-8-1, Jigyohama, Chuo-ku, Fukuoka, 810-8563, Japan

    Takanori Miyoshi & Fuyuki Omura

  2. Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

    Toshinobu Hayashi, Takafumi Nakano & Takashi Egawa

  3. Department of Pharmacy, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan

    Miyuki Uoi

  4. Department of Pharmacy, National Hospital Organization Okinawa Hospital, 3-20-14 Ganeko, Ginowan, Okinawa, 901-22143, Japan

    Kyouichi Tsumagari

  5. Department of Pharmacy, National Hospital Organization Kumamoto Saishun Medical Center, 2659 Suya, Koushi, Kumamoto, 861-1196, Japan

    Sachi Maesaki

  6. Department of Pharmacy, Department of Pharmacy, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Omura, Nagasaki, 856-8562, Japan

    Chiaki Yokota

Authors
  1. Takanori Miyoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshinobu Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miyuki Uoi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fuyuki Omura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kyouichi Tsumagari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sachi Maesaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chiaki Yokota
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Takafumi Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Takashi Egawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TH and TM conceived the study. TH performed statistical analyses. TM, TN, and TE provided technical support. TM, TH, FO, KT, SM, and CY contributed to the interpretation of data and assisted in the preparation of the manuscript. TH and TM prepared the initial draft of the manuscript. TM, TH, FO, KT, SM, CY, TN, and TE critically revised the manuscript. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Toshinobu Hayashi.

Ethics declarations

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committees, and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Consent to participate and/or consent to publication

Not applicable; the requirement for informed consent was waived due to the retrospective nature of the study.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 23 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miyoshi, T., Hayashi, T., Uoi, M. et al. Preventive effect of 20 mEq and 8 mEq magnesium supplementation on cisplatin-induced nephrotoxicity: a propensity score–matched analysis. Support Care Cancer 30, 3345–3351 (2022). https://doi.org/10.1007/s00520-021-06790-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-021-06790-w

Keywords

Search

Navigation