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A systematic review for prevention of cisplatin-induced nephrotoxicity using different hydration protocols and meta-analysis for magnesium hydrate supplementation

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Abstract

Background

Nephrotoxicity remains the most serious side effect of cisplatin therapy. Cisplatin-induced nephrotoxicity (CIN) limits the use of this drug and affects up to 20% of patients. Several possible interventions such as magnesium supplementation may prevent CIN. This study aimed to review different types of hydration protocols and we conducted a meta-analysis of magnesium supplementation to understand its effect in protecting against CIN.

Methods

A search of the PubMed, Embase, and Cochrane databases was performed. Trials were eligible if they enrolled patients who received cisplatin and different hydration protocols to prevent CIN. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the efficacy of different protocols.

Results

We initially identified 1113 different studies and included 33 of them which met the selection criteria. A meta-analysis of 11 retrospective studies that examined magnesium supplementation during hydration showed that this treatment provided significant protection against CIN (OR = 0.22, 95% CI = 0.14 to 0.35).

Conclusion

There has been uncertainty regarding the best method to prevent CIN. Our results highlight the potentially protective effect of magnesium supplementation during hydration. This study is registered in PROSPERO, CRD42020212682.

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Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Kellum JA, Lameire N. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit care (Lond, Engl). 2013;17(1):204. https://doi.org/10.1186/cc11454.

    Article  Google Scholar 

  2. Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet (Lond, Engl). 2019;394(10212):1949–64. https://doi.org/10.1016/s0140-6736(19)32563-2.

    Article  CAS  Google Scholar 

  3. Holditch SJ, Brown CN, Lombardi AM, Nguyen KN, Edelstein CL. Recent advances in models, mechanisms, biomarkers, and interventions in cisplatin-induced acute kidney injury. Int J Mol Sci. 2019;20(12):3011. https://doi.org/10.3390/ijms20123011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hayati F, Hossainzadeh M, Shayanpour S, Abedi-Gheshlaghi Z, Beladi Mousavi SS. Prevention of cisplatin nephrotoxicity. J Nephropharmacol. 2016;5(1):57–60.

    CAS  PubMed  Google Scholar 

  5. Pabla N, Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 2008;73(9):994–1007. https://doi.org/10.1038/sj.ki.5002786.

    Article  CAS  PubMed  Google Scholar 

  6. Crona DJ, Faso A, Nishijima TF, McGraw KA, Galsky MD, Milowsky MI. A systematic review of strategies to prevent cisplatin-induced nephrotoxicity. Oncologist. 2017;22(5):609–19. https://doi.org/10.1634/theoncologist.2016-0319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Amirshahrokhi K, Khalili AR. Thalidomide ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in an experimental model. Inflammation. 2015;38(2):476–84. https://doi.org/10.1007/s10753-014-9953-7.

    Article  CAS  PubMed  Google Scholar 

  8. Higuchi K, Yanagawa T. Evaluating dose of cisplatin responsible for causing nephrotoxicity. PLoS ONE. 2019;14(4): e0215757. https://doi.org/10.1371/journal.pone.0215757.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of cisplatin nephrotoxicity. Toxins. 2010;2(11):2490–518. https://doi.org/10.3390/toxins2112490.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Latcha S, Jaimes EA, Patil S, Glezerman IG, Mehta S, Flombaum CD. Long-term renal outcomes after cisplatin treatment. Clin J Am Soc Nephrol CJASN. 2016;11(7):1173–9. https://doi.org/10.2215/cjn.08070715.

    Article  CAS  PubMed  Google Scholar 

  11. Faig J, Haughton M, Taylor RC, D’Agostino RB Jr, Whelen MJ, Porosnicu Rodriguez KA, et al. Retrospective analysis of cisplatin nephrotoxicity in patients with head and neck cancer receiving outpatient treatment with concurrent high-dose cisplatin and radiotherapy. Am J Clin Oncol. 2018;41(5):432–40. https://doi.org/10.1097/coc.0000000000000301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Horinouchi H, Kubota K, Miyanaga A, Nakamichi S, Seike M, Gemma A, et al. Oral rehydration solution (OS-1) as a substitute of intravenous hydration after cisplatin administration in patients with lung cancer: a prospective multicenter trial. ESMO Open. 2018;3(1): e000288. https://doi.org/10.1136/esmoopen-2017-000288.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: a review. Res Synth Methods. 2019;10(4):486–96. https://doi.org/10.1002/jrsm.1346.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Nahm FS. What the P values really tell us. Korean J Pain. 2017;30(4):241–2. https://doi.org/10.3344/kjp.2017.30.4.241.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Aoyama T, Tsunoda T, Kato H, Hagino A, Furutani R, Ito K, et al. Comparison of cisplatin-induced nephrotoxicity when using conventional versus short hydration in gastric cancer-a retrospective study. J Chemother (Florence, Italy). 2020;32(3):144–50. https://doi.org/10.1080/1120009x.2020.1713507.

    Article  CAS  Google Scholar 

  16. Ashrafi F, Ebrahimi Z, Nematbakhsh M. Effect of short hydration on cisplatin-induced nephrotoxicity in cancer patients: a retrospective study. Int J Hematol Oncol Stem Cell Res. 2017;11(4):262–7.

    PubMed  PubMed Central  Google Scholar 

  17. Ashrafi F, Erfani M, Mousavi S. The effect of hydration therapy with and without magnesium sulfate on prevention of cisplatin-induced nephrotoxicity. Iran J Blood Cancer. 2019;11(1):13–7.

    Google Scholar 

  18. Azuma T, Matayoshi Y, Sato Y, Sato Y, Nagase Y, Oshi M. The safety and effect of chemotherapy with short hydration for urothelial cancer on patients’ quality of life. Jpn J Clin Oncol. 2016;46(10):958–63. https://doi.org/10.1093/jjco/hyw097.

    Article  PubMed  Google Scholar 

  19. Bodnar L, Wcislo G, Gasowska-Bodnar A, Synowiec A, Szarlej-Wcisło K, Szczylik C. 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 (Oxf, Engl: 1990). 2008;44(17):2608–14. https://doi.org/10.1016/j.ejca.2008.08.005.

  20. El Hamamsy M, Kamal N, Bazan NS, El Haddad M. Evaluation of the effect of acetazolamide versus mannitol on cisplatin-induced nephrotoxicity, a pilot study. Int J Clin Pharm. 2018;40(6):1539–47. https://doi.org/10.1007/s11096-018-0677-x.

    Article  CAS  PubMed  Google Scholar 

  21. Hotta K, Takigawa N, Hisamoto-Sato A, Ichihara E, Kudo K, Uchida K, et al. 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. 2013;43(11):1115–23. https://doi.org/10.1093/jjco/hyt128.

    Article  PubMed  Google Scholar 

  22. Kidera Y, Kawakami H, Sakiyama T, Okamoto K, Tanaka K, Takeda M, et al. Risk factors for cisplatin-induced nephrotoxicity and potential of magnesium supplementation for renal protection. PLoS ONE. 2014;9(7): e101902. https://doi.org/10.1371/journal.pone.0101902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 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(1):10. https://doi.org/10.1186/s40463-018-0261-3.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Puisset F, Bigay-Game L, Paludetto MN, Martel A, Perriat S, Rabeau A, et al. Safety of oral hydration after cisplatin infusion in an outpatient lung cancer unit. Support Care Cancer Off J Multinatl Assoc Support Care Cancer. 2019;27(5):1679–86. https://doi.org/10.1007/s00520-018-4415-7.

    Article  Google Scholar 

  25. Tiseo M, Martelli O, Mancuso A, Sormani MP, Bruzzi P, Di Salvia R, et al. Short hydration regimen and nephrotoxicity of intermediate to high-dose cisplatin-based chemotherapy for outpatient treatment in lung cancer and mesothelioma. Tumori. 2007;93(2):138–44.

    Article  CAS  PubMed  Google Scholar 

  26. Lavolé A, Danel S, Baudrin L, Gounant V, Ruppert AM, Epaud C, et al. Routine administration of a single dose of cisplatin ≥ 75 mg/m2 after short hydration in an outpatient lung-cancer clinic. Bull Cancer. 2012;99(4):E43–8. https://doi.org/10.1684/bdc.2012.1555.

    Article  PubMed  Google Scholar 

  27. Ouchi A, Asano M, Aono K, Watanabe T, Kato T. Comparison of short and continuous hydration regimen in chemotherapy containing intermediate- to high-dose cisplatin. J Oncol. 2014;2014: 767652. https://doi.org/10.1155/2014/767652.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sakaida E, Iwasawa S, Kurimoto R, Ebata T, Imai C, Oku T, et al. Safety of a short hydration method for cisplatin administration in comparison with a conventional method-a retrospective study. Jpn J Clin Oncol. 2016;46(4):370–7. https://doi.org/10.1093/jjco/hyv203.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Tanaka M, Horinouchi H, Goto Y, Kanda S, Fujiwara Y, Nokihara H, et al. Reduction in nephrotoxicities using short hydration for chemotherapy containing cisplatin: a consecutive analysis of 467 patients with thoracic malignancies. ESMO Open. 2018;3(4): e000342. https://doi.org/10.1136/esmoopen-2018-000342.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Santoso JT, Lucci JA 3rd, Coleman RL, Schafer I, Hannigan EV. Saline, mannitol, and furosemide hydration in acute cisplatin nephrotoxicity: a randomized trial. Cancer Chemother Pharmacol. 2003;52(1):13–8. https://doi.org/10.1007/s00280-003-0620-1.

    Article  CAS  PubMed  Google Scholar 

  31. Muraki K, Koyama R, Honma Y, Yagishita S, Shukuya T, Ohashi R, et al. Hydration with magnesium and mannitol without furosemide prevents the nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced non-small cell lung cancer. J Thorac Dis. 2012;4(6):562–8. https://doi.org/10.3978/j.issn.2072-1439.2012.10.16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. McKibbin T, Cheng LL, Kim S, Steuer CE, Owonikoko TK, Khuri FR, et al. Mannitol to prevent cisplatin-induced nephrotoxicity in patients with squamous cell cancer of the head and neck (SCCHN) receiving concurrent therapy. Support Care Cancer Off J Multinatl Assoc Support Care Cancer. 2016;24(4):1789–93. https://doi.org/10.1007/s00520-015-2978-0.

    Article  Google Scholar 

  33. Mach CM, Kha C, Nguyen D, Shumway J, Meaders KM, Ludwig M, et al. A retrospective evaluation of furosemide and mannitol for prevention of cisplatin-induced nephrotoxicity. J Clin Pharm Ther. 2017;42(3):286–91. https://doi.org/10.1111/jcpt.12509.

    Article  CAS  PubMed  Google Scholar 

  34. Ninomiya K, Hotta K, Hisamoto-Sato A, Ichihara E, Gotoda H, Morichika D, et al. Short-term low-volume hydration in cisplatin-based chemotherapy for patients with lung cancer: the second prospective feasibility study in the Okayama Lung Cancer Study Group Trial 1201. Int J Clin Oncol. 2016;21(1):81–7. https://doi.org/10.1007/s10147-015-0860-1.

    Article  CAS  PubMed  Google Scholar 

  35. Oka T, Kimura T, Suzumura T, Yoshimoto N, Nakai T, Yamamoto N, et al. Magnesium supplementation and high volume hydration reduce the renal toxicity caused by cisplatin-based chemotherapy in patients with lung cancer: a toxicity study. BMC Pharmacol Toxicol. 2014;15:70. https://doi.org/10.1186/2050-6511-15-70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 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 Off J Multinatl Assoc Support Care Cancer. 2017;25(2):481–7. https://doi.org/10.1007/s00520-016-3426-5.

    Article  Google Scholar 

  37. 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(5):379–81. https://doi.org/10.1097/mph.0000000000001159.

    Article  CAS  PubMed  Google Scholar 

  38. Minzi OMS, Lyimo TE, Furia FF, Marealle AI, Kilonzi M, Bwire GM, et al. Electrolytes supplementation can decrease the risk of nephrotoxicity in patients with solid tumors undergoing chemotherapy with cisplatin. BMC Pharmacol Toxicol. 2020;21(1):69. https://doi.org/10.1186/s40360-020-00448-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Vogl SE, Zaravinos T, Kaplan BH, Wollner D. Safe and effective two-hour outpatient regimen of hydration and diuresis for the administration of cis-diamminedichloroplatinum (II). Eur J Cancer (Oxf, Engl: 1990). 1981;17(3):345–50. https://doi.org/10.1016/0014-2964(81)90126-2.

    Article  CAS  Google Scholar 

  40. Williams RP Jr, Ferlas BW, Morales PC, Kurtzweil AJ. Mannitol for the prevention of cisplatin-induced nephrotoxicity: a retrospective comparison of hydration plus mannitol versus hydration alone in inpatient and outpatient regimens at a large academic medical center. J Oncol Pharm Pract Off Publ Int Soc Oncol Pharm Practition. 2017;23(6):422–8. https://doi.org/10.1177/1078155216656927.

    Article  CAS  Google Scholar 

  41. Willox JC, McAllister EJ, Sangster G, Kaye SB. Effects of magnesium supplementation in testicular cancer patients receiving cis-platin: a randomised trial. Br J Cancer. 1986;54(1):19–23. https://doi.org/10.1038/bjc.1986.147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Yoshida T, Niho S, Toda M, Goto K, Yoh K, Umemura S, et al. Protective effect of magnesium preloading on cisplatin-induced nephrotoxicity: a retrospective study. Jpn J Clin Oncol. 2014;44(4):346–54. https://doi.org/10.1093/jjco/hyu004.

    Article  PubMed  Google Scholar 

  43. Yamamoto Y, Watanabe K, Tsukiyama I, Matsushita H, Yabushita H, Matsuura K, et al. Nephroprotective effects of hydration with magnesium in patients with cervical cancer receiving cisplatin. Anticancer Res. 2015;35(4):2199–204.

    CAS  PubMed  Google Scholar 

  44. Yamamoto Y, Watanabe K, Tsukiyama I, Yabushita H, Matsuura K, Wakatsuki A. Hydration with 15 mEq magnesium is effective at reducing the risk for cisplatin-induced nephrotoxicity in patients receiving cisplatin (≥50 mg/m2) combination chemotherapy. Anticancer Res. 2016;36(4):1873–7.

    CAS  PubMed  Google Scholar 

  45. 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 Off J Multinatl Assoc Support Care Cancer. 2017;25(4):1215–20. https://doi.org/10.1007/s00520-016-3512-8.

    Article  Google Scholar 

  46. Horinouchi H, Kubota K, Itani H, Taniyama TK, Nakamichi S, Wakui H, et al. Short hydration in chemotherapy containing cisplatin (≥75 mg/m2) for patients with lung cancer: a prospective study. Jpn J Clin Oncol. 2013;43(11):1105–9. https://doi.org/10.1093/jjco/hyt122.

    Article  PubMed  Google Scholar 

  47. Launay-Vacher V, Rey JB, Isnard-Bagnis C, Deray G, Daouphars M. Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Cancer Chemother Pharmacol. 2008;61(6):903–9. https://doi.org/10.1007/s00280-008-0711-0.

    Article  CAS  PubMed  Google Scholar 

  48. Hamroun A, Lenain R, Bigna JJ, Speyer E, Bui L, Chamley P, et al. Prevention of cisplatin-induced acute kidney injury: a systematic review and meta-analysis. Drugs. 2019;79(14):1567–82. https://doi.org/10.1007/s40265-019-01182-1.

    Article  PubMed  Google Scholar 

  49. Tong GM, Rude RK. Magnesium deficiency in critical illness. J Intensive Care Med. 2005;20(1):3–17. https://doi.org/10.1177/0885066604271539.

    Article  PubMed  Google Scholar 

  50. Chintala V, Prabhu VM, Boyanagari M, Bhat AN. Role of hypomagnesaemia in acute kidney injury. J Clin Diagn Res. 2018. https://doi.org/10.7860/JCDR/2018/28073.11329.

    Article  Google Scholar 

  51. Kumar G, Solanki MH, Xue X, Mintz R, Madankumar S, Chatterjee PK, et al. Magnesium improves cisplatin-mediated tumor killing while protecting against cisplatin-induced nephrotoxicity. Am J Physiol Renal Physiol. 2017;313(2):F339–50. https://doi.org/10.1152/ajprenal.00688.2016.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by Grant 81670627 from the National Natural Science Foundation of China, LGY2020035 from the High-level Health Personnel “Six One Project” Talent Project of Jiangsu Provence.

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  1. Juanjuan Li and Yu Wu contributed equally to this work.

Authors and Affiliations

  1. Division of Nephrology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, 68 Gehu Road, Hutang Town, Wujin District, Changzhou, Jiangsu, China

    Juanjuan Li, Yu Wu, Cheng Chen, Wanfen Zhang, Lili Yue & Tongqiang Liu

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  1. Juanjuan Li
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Correspondence to Lili Yue or Tongqiang Liu.

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Li, J., Wu, Y., Chen, C. et al. A systematic review for prevention of cisplatin-induced nephrotoxicity using different hydration protocols and meta-analysis for magnesium hydrate supplementation. Clin Exp Nephrol 28, 1–12 (2024). https://doi.org/10.1007/s10157-023-02386-2

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