The prevention of cisplatin-induced nephrotoxicity: A general consensus statement of a group of oncologist-hematologists, adult and pediatric nephrologists, radiation oncologists, clinical pathologists, clinical pharmacologists, and renal physiologists on cisplatin therapy in cancer patients

Farzaneh Ashrafi; Mojgan Mortazavi; Mehdi Nematbakhsh

doi:10.4103/ijpvm.IJPVM_445_19

ORIGINAL ARTICLE

Year : 2022 | Volume : 13 | Issue : 1 | Page : 21

The prevention of cisplatin-induced nephrotoxicity: A general consensus statement of a group of oncologist-hematologists, adult and pediatric nephrologists, radiation oncologists, clinical pathologists, clinical pharmacologists, and renal physiologists on cisplatin therapy in cancer patients

Farzaneh Ashrafi¹, Mojgan Mortazavi², Mehdi Nematbakhsh³
¹ Water and Electrolytes Research Center, Isfahan University of Medical Sciences; Department of Internal Medicine, Oncology-Hematology Section, Isfahan University of Medical Sciences, Isfahan, Iran
² Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences; Department of Internal Medicine, Nephrology Section, Isfahan University of Medical Sciences, Isfahan, Iran
³ Water and Electrolytes Research Center, Isfahan University of Medical Sciences; Department of Physiology, Isfahan University of Medical Sciences; IsfahanMN Institute of Basic and Applied Sciences Research, Isfahan, Iran

Date of Submission	28-Nov-2019
Date of Acceptance	27-Nov-2020
Date of Web Publication	08-Feb-2022

Correspondence Address:
Mehdi Nematbakhsh
Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan
Iran

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ijpvm.IJPVM_445_19

Abstract

Backgrounds: Most of the cancer patients with solid tumor are subjected to chemotherapy with cisplatin (CP) in clinic. However, the most side effect of CP is nephrotoxicity, which limits the treatment. The aim of study was to develop a general consensus statement for CP therapy in clinic to limit the drug-induced nephrotoxicity. Methods: A total of 30 oncologist-hematologists, adult and pediatric nephrologists, radiation oncologists, clinical pathologist clinical pharmacologist, and renal physiologist participated in a workshop, and in order to reduce the incidence of CP-induced nephrotoxicity, a general consensus was developed. Results: The developed general consensus was focused on some items such as age, sex, female hormone, nonsteroidal anti-inflammatory drugs (NSAID), renin–angiotensin system inhibitor drugs, glomerular filtration rate, hydration methods, contrasts, antioxidants, dextrose, and magnesium. Conclusion: The agreement between participants for CP therapy in clinic was achieved, and this general consensus was announced to be implemented in the hospitals.

Keywords: Cisplatin, consensus, nephron, toxicity

How to cite this article:
Ashrafi F, Mortazavi M, Nematbakhsh M. The prevention of cisplatin-induced nephrotoxicity: A general consensus statement of a group of oncologist-hematologists, adult and pediatric nephrologists, radiation oncologists, clinical pathologists, clinical pharmacologists, and renal physiologists on cisplatin therapy in cancer patients. Int J Prev Med 2022;13:21

How to cite this URL:
Ashrafi F, Mortazavi M, Nematbakhsh M. The prevention of cisplatin-induced nephrotoxicity: A general consensus statement of a group of oncologist-hematologists, adult and pediatric nephrologists, radiation oncologists, clinical pathologists, clinical pharmacologists, and renal physiologists on cisplatin therapy in cancer patients. Int J Prev Med [serial online] 2022 [cited 2023 Sep 28];13:21. Available from: https://www.ijpvmjournal.net/text.asp?2022/13/1/21/337393

Introduction

Cisplatin (CP) is the most frequently used drug for cancer treatment. Acute kidney injury, glomerular capillary endothelial injury, tubulointrestitial disease, and renal electrolyte disorders are the most frequent adverse effects of CP therapy, which are major causes of morbidity and mortality among cancer patients. Volume depletion, preexisting kidney disease, cardiovascular disease, diabetes, and concurrent use of nonsteroidal other nephrotoxic drugs such as nonsteroidal anti-inflammatory drugs (NSAID) are the major risk factors for CP-induced nephrotoxicity.

There are some risk factors associated with the incidence of CP-induced nephrotoxicity.^[1] In addition, many other clinical and experimental studies have explained the CP-induced nephrotoxicity risk factors, including age,^[2],[3],[4] gender,^[5],[6],[7] low glomerular filtration rate (GFR),^[8] sex hormone estrogen,^[9] dehydration,^[8] hydration process during CP therapy with dextrose,^[10] NSAID, and contrast media.^[11] Special attentions also were made to antioxidant therapy to attenuate CP-induced nephrotoxicity in the laboratory.^{[12],[13],[14],[15],[16]} Based on new findings, the general consensus will be helpful to prevent nephrotoxicity during CP therapy.

Methods

A total of 30 oncologist-hematologists, adult and pediatrics' nephrologists, radiation oncologists, clinical pathologists, clinical pharmacologist, and renal physiologists participated in a workshop to develop a general consensus to reduce the incidence of CP-induced nephrotoxicity in Isfahan, Iran hospitals. The announcement for the workshop was performed 2 months earlier, and the participants were asked to review the related materials in the literature including their experiences to obtain the general consensus questions. Based on the suggestions, four main subjects related to CP therapy were assigned for the workshop discussion as followings:

Based on the clinical evidences, to reduce the CP-induced nephrotoxicity, the CP prescribing should be accompanied by hydration of the patient. Therefore, the agreement on the hydration process seems necessary.
Based on the experimental evidences, some synthetic and herbal antioxidant supplements can reduce CP-induced nephrotoxicity, and it seems necessary to agree on this issue in the process of CP therapy.
From the clinical point of view, the patients should have favorable clinical conditions for receiving CP (e.g., the minimum level of GFR) and therefore agreeing to these issues in the CP prescribing process seems essential.
Some drugs along with CP increases the risk of nephrotoxicity and it is therefore necessary to agree on these issues in the process of CP prescribing.

The subjects with the 16 questions were submitted to the participants before the workshop day. On the day of workshop, two nephrologists and two oncologist-hematologists also were asked to summarize the literature reviewing results. During the discussion, some other questions also were created by the participants.

Therefore, all questions, one by one, were subjected to panel discussion, and based on the opinion of all, the agreement was created. Finally, three workshop members were assigned to prepare the draft of general consensus, and then the draft was finalized. This general consensus included 13 principals or important items that must be considered during CP therapy to limit CP-induced nephrotoxicity.

Results

The general consensus included four different parts.

Part one: general consideration factors include 4 items (principals 1–4)

The general consideration factors were listed in [Table 1]. Age, gender, concurrent use of renin–angiotensin system inhibitor drugs, the level of female sex hormone estrogen, and estimated GFR should be considered in the first step.

Table 1: A general consensus statement on cisplatin therapy in cancer patients: the associated items and factors and principals

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Part two: prohibition items include 6 items (principals 5–10)

To avoid CP-induced nephrotoxicity, some items are forbidden during CP therapy, including GFR <50 ml/min/1.73 m² body surface, hydration with dextrose, NSAID prescribing, given contrast media during 2 weeks post-CP administration, and prescribing antioxidant without enough clinical evidences [Table 1]. Due to existence of positive and negative results for mannitol prescribing,^{[17],[18],[19],[20],[21]} special care is recommended when mannitol administration is applied.

Part three: requirement and permission items include 2 items (principals 11–12)

There are two major requirements and a major license. Before and after administration of CP, hydration should be performed with normal saline plus potassium chloride (KCl). Administration of intravenous magnesium with hydration is recommended only when the serum level of magnesium is lower than normal [Table 1].[45]

Part four: Others include 1 item (principal 13)

There are many other pathological conditions such as diabetes, kidney transplantation, acidosis, hypokalemia, hyperuricemia infection, etc. that need to be considered on a case-by-case basis.

Conclusion

We suggested several new points that need to be considered during CP administration. Female sex hormone estrogen,^{[9],[25],[26],[27],[28]} hydration with dextrose,^[10],[31] and concurrent use of renin–angiotensin system inhibitor drugs^{[5],[23],[24]} are the subjects that included in this general consensus. In order to obtain a more complete general consensus or guideline for CP therapy, more clinical trial researches are needed.

Author contribution

All the authors (FA, MM, and MN) were contributed to design the workshop, to search the main literature review, to manage the workshop, and to wright the article draft. The article was finalized by MN.

Acknowledgements

Special thanks to the entire workshop participants for their thoughtful reviewing and discussing; Dr Fariborz Mokarian, Dr Shahrzad Shahidi, Dr Mohammad Matinfar, Dr Shahram Taheri, Dr Abdolamir Atapoor, Dr Hamid Nasri, Dr Valiollah Mahrzad, Dr Alaleh Gheisari, Dr Shiva Seirafian, Dr Mehdi Mahmoodzadeh, Dr Firoozeh Moeinzadeh, Dr Mehran Sharifi, Dr Alireza Sadeghi, Dr Nooshin Hashemi, Dr Maryam Mirpoorian, Dr Padideh Oghab, Dr Reihaneh Motamedifard, Dr Ali Akhavan, Dr Farhad Ghadiri, Dr Ali Derakhshandeh, Dr Yaser Salehi, Dr Mohammad-Reza Khosravi, Dr Shirinsadat Badri, Dr Ziba Farajzadeghan, Dr Ardeshir Talebi, Dr Yousef Gheisari, and Dr Aliraza Andalib. Additional thanks to Dr Fariborz Mokarian, Dr Shahrzad Shahidi, Dr Mohammad Matinfar for their lectures in the workshop.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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