• Users Online: 4420
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Browse Articles Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
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

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 Submission28-Nov-2019
Date of Acceptance27-Nov-2020
Date of Web Publication08-Feb-2022

Correspondence Address:
Mehdi Nematbakhsh
Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpvm.IJPVM_445_19

Rights and Permissions

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 Top

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 Top

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:

  1. 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.
  2. 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.
  3. 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.
  4. 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 Top

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

Click here to view

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 Top

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.


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


Conflicts of interest

There are no conflicts of interest.

  References Top

Sanchez-Gonzalez PD, Lopez-Hernandez FJ, Lopez-Novoa JM, Morales AI. An integrative view of the pathophysiological events leading to cisplatin nephrotoxicity. Crit Rev Toxicol 2011;41:803-21.  Back to cited text no. 1
de Jongh FE, van Veen RN, Veltman SJ, de Wit R, van der Burg ME, van den Bent MJ, et al. Weekly high-dose cisplatin is a feasible treatment option: Analysis on prognostic factors for toxicity in 400 patients. B J Cancer 2003;88:1199-206.  Back to cited text no. 2
Pezeshki Z, Maleki M, Talebi A, Nematbakhsh M. Age and gender related renal side effects of cisplatin in animal model. Asian Pac J Cancer Prev 2017;18:1703-5.  Back to cited text no. 3
Ali BH, Al-Moundhri M, Tageldin M, Al Husseini IS, Mansour MA, Nemmar A, et al. Ontogenic aspects of cisplatin-induced nephrotoxicity in rats. Food Chem Toxicol 2008;46:3355-9.  Back to cited text no. 4
Nematbakhsh M, Pezeshki Z, Eshraghi Jazi F, Mazaheri B, Moeini M, Safari T, et al. Cisplatin-induced nephrotoxicity; protective supplements and gender differences. Asian Pac J Cancer Prev 2017;18:295-314.  Back to cited text no. 5
Aydin I, Agilli M, Aydin FN. Gender differences influence renal injury in cisplatin-treated rats: Biochemical evaluation. Biol Trace Elem Res 2014;158:275.  Back to cited text no. 6
Nematbakhsh M, Ebrahimian S, Tooyserkani M, Eshraghi-Jazi F, Talebi A, Ashrafi F. Gender difference in Cisplatin-induced nephrotoxicity in a rat model: Greater intensity of damage in male than female. Nephrourol Mon 2013;5:818-21.  Back to cited text no. 7
Isnard-Bagnis C, Moulin B, Launay-Vacher V, Izzedine H, Tostivint I, Deray G. [Anticancer drug-induced nephrotoxicity]. Nephrol Ther 2005;1:101-14.  Back to cited text no. 8
Pezeshki Z, Nematbakhsh M, Nasri H, Talebi A, Pilehvarian AA, Safari T, et al. Evidence against protective role of sex hormone estrogen in Cisplatin-induced nephrotoxicity in ovarectomized rat model. Toxicol Int 2013;20:43-7.  Back to cited text no. 9
[PUBMED]  [Full text]  
Karimi F, Kassaei S, Baradaran A, Ashrafi F, Talebi A, Lak Z, et al. Dextrose hydration may promote cisplatin-induced nephrotoxicity in rats: Gender-related difference. Indones Biomed J 2019;11:136-44.  Back to cited text no. 10
Jones DP, Spunt SL, Green D, Springate JE, Children's Oncology G. Renal late effects in patients treated for cancer in childhood: A report from the Children's oncology group. Pediatr Blood Cancer 2008;51:724-31.  Back to cited text no. 11
Kamel KM, Abd El-Raouf OM, Metwally SA, Abd El-Latif HA, El-sayed ME. Hesperidin and rutin, antioxidant citrus flavonoids, attenuate cisplatin-induced nephrotoxicity in rats. J Biochem Mol Toxicol 2014;28:312-9.  Back to cited text no. 12
Somani SM, Husain K, Whitworth C, Trammell GL, Malafa M, Rybak LP. Dose-dependent protection by lipoic acid against cisplatin-induced nephrotoxicity in rats: Antioxidant defense system. Pharmacol Toxicol 2000;86:234-41.  Back to cited text no. 13
Nematbakhsh M, Pezeshki Z. Sex-related difference in nitric oxide metabolites levels after nephroprotectant supplementation administration against cisplatin-induced nephrotoxicity in wistar rat model: The role of vitamin E, erythropoietin, or N-Acetylcysteine. ISRN Nephrol 2013;2013:612675.  Back to cited text no. 14
Nematbakhsh M, Ashrafi F, Safari T, Talebi A, Nasri H, Mortazavi M, et al. Administration of vitamin E and losartan as prophylaxes in cisplatin-induced nephrotoxicity model in rats. J Nephrol 2012;25:410-7.  Back to cited text no. 15
Atasayar S, Gurer-Orhan H, Orhan H, Gurel B, Girgin G, Ozgunes H. Preventive effect of aminoguanidine compared to vitamin E and C on cisplatin-induced nephrotoxicity in rats. Exp Toxicol Pathol 2009;61:23-32.  Back to cited text no. 16
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;40:1539-47.  Back to cited text no. 17
Dhillon P, Amir E, Lo M, Kitchlu A, Chan C, Cochlin S, et al. A case-control study analyzing mannitol dosing for prevention of cisplatin-induced acute nephrotoxicity. J Oncol Pharm Pract 2019;25:875-83.  Back to cited text no. 18
Adam JP, Fournier MA, Letarte N. Should mannitol be reinstated in prevention of cisplatin-induced nephrotoxicity? J Oncol Pharm Pract 2018;24:239-40.  Back to cited text no. 19
Morgan KP, Buie LW, Savage SW. The role of mannitol as a nephroprotectant in patients receiving cisplatin therapy. Ann Pharmacother 2012;46:276-81.  Back to cited text no. 20
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 2017;23:422-8.  Back to cited text no. 21
Launay-Vacher V, Isnard-Bagnis C, Janus N, Karie S, Deray G. [Chemotherapy and renal toxicity]. Bull Cancer 2008;95 FMC Onco:F96-103.  Back to cited text no. 22
Zamani Z, Nematbakhsh M, Eshraghi-Jazi F, Talebi A, Jilanchi S, Navidi M, et al. Effect of enalapril in cisplatin-induced nephrotoxicity in rats; gender-related difference. Adv Biomed Res 2016;5:14.  Back to cited text no. 23
[PUBMED]  [Full text]  
Haghighi M, Nematbakhsh M, Talebi A, Nasri H, Ashrafi F, Roshanaei K, et al. The role of angiotensin II receptor 1 (AT1) blockade in cisplatin-induced nephrotoxicity in rats: Gender-related differences. Ren Fail 2012;34:1046-51.  Back to cited text no. 24
Ghasemi M, Nematbakhsh M, Pezeshki Z, Soltani N, Moeini M, Talebi A. Nephroprotective effect of estrogen and progesterone combination on cisplatin-induced nephrotoxicity in ovariectomized female rats. Indian J Nephrol 2016;26:167-75.  Back to cited text no. 25
[PUBMED]  [Full text]  
Pezeshki Z, Nematbakhsh M, Mazaheri S, Eshraghi-Jazi F, Talebi A, Nasri H, et al. Estrogen abolishes protective effect of erythropoietin against cisplatin-induced nephrotoxicity in ovariectomized rats. ISRN Oncol 2012;2012:890310.  Back to cited text no. 26
Nematbakhsh M, Pezeshki Z, Eshraghi-Jazi F, Ashrafi F, Nasri H, Talebi A, et al. Vitamin E, vitamin C, or losartan is not nephroprotectant against cisplatin-induced nephrotoxicity in presence of estrogen in ovariectomized rat model. Int J Nephrol 2012;2012:284896.  Back to cited text no. 27
Mazaheri S, Nematbakhsh M, Bahadorani M, Pezeshki Z, Talebi A, Ghannadi AR, et al. Effects of fennel essential oil on cisplatin-induced nephrotoxicity in ovariectomized rats. Toxicol Int 2013;20:138-45.  Back to cited text no. 28
[PUBMED]  [Full text]  
Loh JM, Tran AL, Ji L, Groshen S, Daneshmand S, Schuckman A, et al. Baseline glomerular filtration rate and cisplatin- induced renal toxicity in urothelial cancer patients. Clin Genitourinary Cancer 2017. doi: 10.1016/j.clgc.2017.08.016.  Back to cited text no. 29
Salek T, Vesely P, Bernatek J. Estimated glomerular filtration rate in oncology patients before cisplatin chemotherapy. Klin Onkol 2015;28:273-7.  Back to cited text no. 30
Scott LA, Madan E, Valentovic MA. Influence of streptozotocin (STZ)-induced diabetes, dextrose diuresis and acetone on cisplatin nephrotoxicity in Fischer 344 (F344) rats. Toxicology 1990;60:109-25.  Back to cited text no. 31
Fukushima K, Okada A, Oe H, Hirasaki M, Hamori M, Nishimura A, et al. Pharmacokinetic-pharmacodynamic analysis of cisplatin with hydration and mannitol diuresis: The contribution of urine cisplatin concentration to nephrotoxicity. Eur J Drug Metab Pharmacokinet 2018;43:193-203.  Back to cited text no. 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 2016;24:1789-93.  Back to cited text no. 33
Chen MF, Yang CM, Su CM, Hu ML. Vitamin C protects against cisplatin-induced nephrotoxicity and damage without reducing its effectiveness in C57BL/6 mice xenografted with Lewis lung carcinoma. NutrCancer 2014;66:1085-91.  Back to cited text no. 34
Darwish MA, Abo-Youssef AM, Khalaf MM, Abo-Saif AA, Saleh IG, Abdelghany TM. Vitamin E mitigates cisplatin-induced nephrotoxicity due to reversal of oxidative/nitrosative stress, suppression of inflammation and reduction of total renal platinum accumulation. J Biochem Mol Toxicol 2017;31:1-9.  Back to cited text no. 35
Durak I, Ozbek H, Karaayvaz M, Ozturk HS. Cisplatin induces acute renal failure by impairing antioxidant system in guinea pigs: Effects of antioxidant supplementation on the cisplatin nephrotoxicity. Drug Chem Toxicol 2002;25:1-8.  Back to cited text no. 36
Konishi H, Fujiwara H, Itoh H, Shiozaki A, Arita T, Kosuga T, et al. Influence of magnesium and parathyroid hormone on cisplatin-induced nephrotoxicity in esophageal squamous cell carcinoma. Oncol Lett 2018;15:658-64.  Back to cited text no. 37
Saito Y, Okamoto K, Kobayashi M, Narumi K, Furugen A, Yamada T, et al. Magnesium co-administration decreases cisplatin-induced nephrotoxicity in the multiple cisplatin administration. Life Sci 2017;189:18-22.  Back to cited text no. 38
Saito Y, Okamoto K, Kobayashi M, Narumi K, Yamada T, Iseki K. Magnesium attenuates cisplatin-induced nephrotoxicity by regulating the expression of renal transporters. Eur J Pharmacol 2017;811:191-8.  Back to cited text no. 39
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. 40
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:e101902.  Back to cited text no. 41
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. Japanese J Clin Oncol 2014;44:346-54.  Back to cited text no. 42
Soltani N, Nematbakhsh M, Eshraghi-Jazi F, Talebi A, Ashrafi F. Effect of oral administration of magnesium on Cisplatin-induced nephrotoxicity in normal and streptozocin-induced diabetic rats. Nephrourol Mon 2013;5:884-90.  Back to cited text no. 43
Ashrafi F, Haghshenas S, Nematbakhsh M, Nasri H, Talebi A, Eshraghi-Jazi F, et al. The role of magnesium supplementation in cisplatin-induced nephrotoxicity in a rat model: No nephroprotectant effect. Int J Prev Med 2012;3:637-43.  Back to cited text no. 44
Goren MP. Cisplatin nephrotoxicity affects magnesium and calcium metabolism. Med Pediatr Oncol 2003;41:186-9.  Back to cited text no. 45


  [Table 1]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Article Tables

 Article Access Statistics
    PDF Downloaded81    
    Comments [Add]    

Recommend this journal