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Nephrotoxicity: Evidence in Patients Receiving Cisplatin Therapy

Elizabeth A. Duffy
Wendy Fitzgerald
Kelley Boyle
Radha Rohatgi
CJON 2018, 22(2), 175-183 DOI: 10.1188/18.CJON.175-183

Background: Cisplatin has been used as a chemotherapeutic agent to treat many different cancers. A well-known side effect of cisplatin is nephrotoxicity, which is the primary dose-limiting toxicity. Hydration in conjunction with appropriate diuresis can decrease the incidence of nephrotoxicity.

Objectives: This article aims to identify best practices in supportive therapy for patients receiving cisplatin therapy.

Methods: A team was assembled to review research-based evidence and summarize recommendations to address appropriate hydration regimens and forced diuresis for patients receiving cisplatin chemotherapy.

Findings: After a systematic search of the literature, only one pediatric study was found. The remaining 22 research-based studies of adults were synthesized and critically appraised. Hydration is necessary to prevent nephrotoxicity with cisplatin administration. In addition, the administration of magnesium and mannitol may assist in maintaining renal function and reducing nephrotoxicity in adults receiving cisplatin. Additional research is needed to evaluate outcomes of these interventions in the pediatric population.


Cisplatin is a platinum compound that has been used as a chemotherapeutic agent for many different cancers, including ovarian, testicular, lung, cervical, and bladder cancers (Ruggiero, Rizzo, Trombatore, Maurizi, & Riccardi, 2016; Santoso, Lucci, Coleman, Shafer, & Hannigan, 2003). The primary dose-limiting toxicity of cisplatin is nephrotoxicity, a well-known side effect (Jones, Spunt, Green, & Springate, 2008; Miller, Tadagavadi, Ramesh, & Reeves, 2010). Nephrotoxicity involves glomerular or tubular dysfunction of the kidneys after exposure to medications, other treatments, or toxins (Skinner, 2011). Nephrotoxicity associated with cisplatin is related to accumulation of metabolites in the renal proximal tubule cells of the kidneys, where about 90% of cisplatin undergoes urinary excretion (Ruggiero et al., 2016). Accumulation of these metabolites causes direct inflammation; the production of reactive oxygen species, which leads to oxidative cell damage; and cell death (Miller et al., 2010; Ruggiero et al., 2016). Many methods are available to measure kidney function and define nephrotoxicity or acute kidney injury (see Table 1).

Most patients receiving cisplatin experience acute impairment of glomerular and tubular function in varying degrees. Toxicity is dependent on individual cisplatin pharmacokinetics and is usually more severe with high total cisplatin doses and when other potential nephrotoxic medications are given concurrently (Skinner, 2011; Womer, Pritchard, & Barratt, 1985). In one study, children aged 10 years or older at treatment had a lower glomerular filtration rate 10 years after therapy compared to children aged younger than 10 years at treatment (Skinner et al., 2009).

Nephrotoxicity can be reversible, but for some individuals, it can result in permanent kidney injury, chronic progressive renal failure, or renal tubule function impairment (Skinner et al., 2009). Chronic and severe reductions of renal function have several sequelae. The immediate impact may be dose reduction or cessation of potentially lifesaving nephrotoxic chemotherapy, thereby increasing the risk of relapse or progression of the cancer. In the event of a disease relapse or progression, changes to renal function may limit enrollment in phase 1 or 2 clinical trials because of inclusion parameters related to baseline renal function.

Hydration and diuretics have been used in conjunction with cisplatin administration for decades to improve the excretion of cisplatin and reduce the incidence of nephrotoxicity. One method of promoting this excretion is through osmotic diuresis with mannitol (Morgan et al., 2014). However, the amount of hydration, the infusion time for hydration, and the use of diuretics vary among treatment protocols. The optimal hydration and diuretic regimen necessary to prevent cisplatin nephrotoxicity is unknown.

Evidence-Based Guideline Development Methods

To identify best practices, the current authors conducted a systematic review to identify optimal hydration and diuretic regimens to prevent nephrotoxicity in patients receiving cisplatin therapy. The team included a pediatric nurse practitioner as team leader, a pharmacist, two nurses, and a mentor with experience in evidence-based reviews.

The team developed the following two clinical questions that helped identify a population, intervention, and outcome (Melnyk & Fineout-Overholt, 2015) to guide the systematic review:

•  Among patients receiving cisplatin chemotherapy (including various doses and infusion duration), what is an appropriate regimen of hydration and/or forced diuresis to prevent or decrease the incidence of nephrotoxicity?

•  Among patients receiving cisplatin chemotherapy (including various doses and infusion duration), what regimen of hydration and/or forced diuresis promotes kidney function?

A systematic search of the literature was performed with guidance from a medical librarian. The search included the following databases: PubMed, CINAHL®, and the Cochrane Library. Keywords and Medical Subject Heading (MeSH) terms consisted of cisplatin, nephrotoxicity and nephrotoxicity prevention, mannitol, hydration, magnesium, diuresis, mannitol, and furosemide. Limits were set for the English language and human studies. None were set regarding patient age in an effort to find all evidence related to the topic. Research studies, meta-analyses, and guidelines were included. In addition, the team searched the websites of the American Society of Clinical Oncology, the Oncology Nursing Society, and the Association of Pediatric Hematology/Oncology Nurses, and Wolters Kluwer’s UpToDate site for guidelines related to the topic.

The initial search was conducted in March 2015 with no publication limit identified. A repeat search of the literature was performed in March 2016 using the same databases, keywords and MeSH terms, and limits. A publication date limit of March 2015 to March 2016 was applied to the repeat search and revealed six new articles. Figure 1 illustrates the literature exclusion process. Based on expert consensus of the team, articles that evaluated oral fluids as the sole source of hydration were excluded because of the improbability of patients tolerating large volumes of oral hydration during chemotherapy treatment. In addition, articles including hypertonic saline were excluded because no clinical indication suggests the use of this fluid for routine hydration (Platania, Verzoni, & Vitali, 2015). Ultimately, 23 articles were identified, which included all age ranges and which are summarized in the current evidence-based review. Only one pediatric study was discovered in the search, which is summarized. Most of this review consists of a synthesis of evidence from studies of adults. The evidence quality was graded using the Grading of Recommendations Assessment, Development, and Evaluation system (Guyatt et al., 2011).

Four clinical practice guidelines were identified from the search. One guideline (UpToDate) was not included because of its paucity of references; two guidelines from the American Society of Clinical Oncology were excluded because they did not include recommendations regarding hydration or diuresis. The remaining guideline by Launay-Vacher, Rey, Isnard-Bagnis, Deray, and Daouphars (2008) was evaluated with the Appraisal of Guidelines for Research and Evaluation II tool. Because of its low rating, the authors did not include this guideline in the body of evidence.

Evidence Review

Pediatric Review

Zareifar et al. (2013) evaluated tubular kidney function in a cohort of 20 children receiving cisplatin 50–75 mg/m2 every three weeks for treatment of neuroblastoma or germ cell tumors. Children received 3 L/m2 of hydration and mannitol every 6 hours starting 24 hours before cisplatin and continuing for one day following cisplatin. The children also received magnesium sulfate infusions every 12 hours for a total of four doses. No significant change in the mean glomerular function rate was observed before cisplatin treatment (119.81 ml/minute/1.73 m2, SD = 36.82) compared to the mean after the third cisplatin treatment (127.37 ml/minute/1.73 m2, SD = 38.99, p = 0.638).


Nephrotoxicity was described in nine studies among adults receiving cisplatin therapy by either comparing hydration regimens, short versus traditional hydration (n = 4), or evaluating renal outcomes with one specific hydration regimen (n = 5). A short hydration regimen was commonly delivered on an outpatient basis and ranged from 1,750–4,200 ml of fluid delivered on the day of cisplatin therapy, whereas a traditional hydration regimen was commonly delivered on an inpatient basis and consisted of a total of 5,500–6,300 ml of fluid delivered during multiple days (see Table 2).



No statistically significant difference in renal function or nephrotoxicity was reported among adults receiving short versus traditional hydration regimens (Al Bahrani, Moylan, Forouzesh, Della-Fiorentina, & Goldrick, 2009; Oka et al., 2014; Ouchi, Asano, Aono, Watanabe, & Kato, 2014). In two of the studies, serum creatinine (SCR) and creatinine clearance (CRCL) were stable between both groups (Al Bahrani et al., 2009; Ouchi et al., 2014); however, one study showed a significant increase in SCR among the traditional hydration group members, whereas the SCR of the short hydration group members remained stable (Sakaida et al., 2016). In addition, no significant differences were observed in renal toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, among individuals receiving traditional versus short hydration regimens (Oka et al., 2014; Ouchi et al., 2014). However, grade 2 toxicity was noted among one of the 17 adult patients receiving 2.2 L of fluid on the day of cisplatin followed with oral hydration (Oka et al., 2014).

Five studies described renal function or nephrotoxicity after patients received short hydration (from 1,400–3,000 ml) of fluid on the day of cisplatin administration. Most studies revealed that short hydration was safe in preventing renal dysfunction and toxicity (Horinouchi et al., 2013; Hotta et al., 2013; Lavolé et al., 2012; Tiseo et al., 2007; Vogl, Zaravinos, Kaplan, & Wollner, 1981). After several courses of cisplatin, only 3 of 242 patients had SCR levels greater than 2 mg/dl and 1 patient had a SCR level greater than 3 mg/dl (Vogl et al., 1981). Other evidence reported no significant change in median SCR or median CRCL among adults receiving multiple cycles of cisplatin at 75 mg/m2 or greater (Tiseo et al., 2007). After multiple cisplatin cycles, a grade 2 or higher renal toxicity according to CTCAE, version 4.0, was noted in only 0.3%–8.6% of patients receiving 1,450–2,250 ml hydration on the day of cisplatin (Horinouchi et al., 2013; Hotta et al., 2013; Lavolé et al., 2012).


Seven studies evaluated magnesium as an IV supplement, an additive to IV hydration, and/or an oral supplement. Results indicated either an increase in CRCL along with a decrease in SCR (Muraki et al., 2012) or stable CRCL and SCR (Bodnar et al., 2008; Oka et al., 2014; Willox, McAllister, Sangster, & Kaye, 1986; Yamamoto et al., 2015) when patients received magnesium supplementation before, during, or after cisplatin therapy. Among the studies reporting nephrotoxicity according to CTCAE, less nephrotoxicity was noted in patients who received magnesium supplements compared to the control groups (Kidera et al., 2014; Yoshida et al., 2014). In addition, a lower relative risk of nephrotoxicity according to the Risk, Injury, Failure, Loss, and End-Stage kidney disease classification was noted among patients receiving magnesium compared to patients who did not receive magnesium (7% versus 50% risk, p = 0.03) (Yamamoto et al., 2015). Patients who did not receive magnesium supplements had a statistically significant decrease in CRCL and statistically significant increase in SCR (Bodnar et al., 2008; Oka et al., 2014). In addition, multivariate analysis revealed that the absence of magnesium infusion was a significant independent factor for decreased CRCL (p < 0.001) (Oka et al., 2014). Bodnar et al. (2008) and Willox et al. (1986) treated patients with magnesium three times per day in between chemotherapy cycles, but no evidence suggested that this provided any additional nephroprotection to the regimen.


Three studies examined the role of furosemide in cisplatin-associated nephrotoxicity. Ostrow et al. (1981) found no significant differences in SCR, CRCL, or nephrotoxicity among patients receiving furosemide 40 mg immediately prior to cisplatin compared to mannitol 37.5 g by a six-hour infusion with cisplatin. The authors concluded that both diuretics exhibited similar effects. Other researchers retrospectively evaluated 50 patients to compare the effect of hydration with magnesium sulfate and mannitol versus hydration with furosemide 20 mg and mannitol on cisplatin-associated nephrotoxicity (Muraki et al., 2012). Hydration with magnesium and mannitol was an independent factor in the protection of patients against nephrotoxicity induced by cisplatin. Finally, mean SCR concentrations were significantly higher in patients who received furosemide 20 mg/m2 one hour prior to cisplatin versus those who did not receive furosemide prior to cisplatin, although no significant differences in CRCL were observed between groups (Dumas et al., 1989).


Seven studies evaluated the effect of mannitol on cisplatin-related nephrotoxicity. Three trials found no clear indication that mannitol is nephroprotective among adults receiving cisplatin (Leu & Baribeault, 2010; Ostrow et al., 1981; Santoso et al., 2003). In one study of 22 patients receiving cisplatin, 28% of patients who received mannitol developed nephrotoxicity compared to 19% of patients in the furosemide group, with the authors concluding that neither mannitol nor furosemide was superior in reducing the frequency of nephrotoxicity (Ostrow et al., 1981). In another study, no significant difference in CRCL was noted among patients receiving mannitol and hydration compared to hydration alone (Leu & Baribeault, 2010). Santoso et al. (2003) found mannitol dosages of 50 g to be significantly nephrotoxic and terminated the study prematurely because patients developed nephrotoxicity.

Four studies revealed that mannitol in conjunction with high-dose cisplatin has a protective effect that allows patients to tolerate cisplatin without nephrotoxicity (Al-Sarraf et al., 1982; McKibbin et al., 2016; Morgan et al., 2014; Muraki et al., 2012). Patients who received mannitol and magnesium demonstrated a significantly greater increase in CRCL (p = 0.004) and decrease in SCR (p = 0.0148) compared to patients receiving hydration with mannitol, magnesium, and furosemide (Muraki et al., 2012). Morgan et al. (2014) also found improved outcomes in patients who received mannitol, and reported a 2.6 increased likelihood of developing acute kidney injury among adults who did not receive mannitol with cisplatin (95% confidence interval [1.008, 6.944], p = 0.048). They recommended the addition of mannitol with hydration to prevent cisplatin-induced nephrotoxicity.

Quality of the Evidence

The quality of the hydration evidence was based on nine research articles. The evidence consisted of six retrospective studies and three prospective studies (one nonrandomized, single-center, phase 2 study; one feasibility study; and one cohort study). Issues related to the quality of the evidence included no report of power analysis in all studies, inconsistency issues among comparison groups in two studies, and one potential publication bias because of a long lag time from study completion to publication. The overall body of evidence for hydration was of low quality.

The magnesium evidence was based on seven research articles consisting of two randomized clinical trials, four retrospective chart reviews, and one historical prospective cohort study. Issues related to the quality of the evidence included lack of reported power analyses in all studies. The overall body of evidence for magnesium was of low quality.

The furosemide evidence is based on three research articles consisting of two randomized, prospective, controlled studies and one retrospective chart review. Issues related to the quality of the evidence included lack of reported power analyses in all studies. The overall body of evidence for furosemide was of low quality.

The mannitol evidence is based on seven research studies. The designs consisted of four retrospective studies and three prospective studies (two randomized, controlled studies and one phase 2 study). Issues related to the quality of the evidence included lack of reported power analysis in all studies. The overall body of evidence for mannitol was of low quality.

Summary of Recommendations

Hydration is necessary to prevent nephrotoxicity with cisplatin administration; however, the amount, duration, and timing of hydration for patients cannot be determined from the limited evidence. In addition, administration of magnesium and mannitol may assist in maintaining renal function and reducing nephrotoxicity in adults receiving cisplatin; however, limited evidence precludes the ability to provide recommendations for children. More research is needed to identify best practices for patients.


Limitations in the literature review include limited evidence about the variation of practice patterns in different settings. There could be differences in patient management, particularly hydration regimens and the use of diuretics, which varies depending on treatment setting. More research is needed to identify these differences.

In addition, the literature is limited because of the inclusion of diverse age groups. Only one pediatric study evaluated nephrotoxicity in children receiving cisplatin therapy, requiring more evaluation so conclusions can be determined among the pediatric population. Also, insufficient literature prevented the authors from subcategorizing the adult population by age; additional research should be conducted to evaluate the nephrotoxicity differences among young, middle-aged, and older adult patients.

Last, this literature review does not include the effects of other medications on nephrotoxicity. Researchers should consider investigating the influence of nephrotoxic medications on people receiving cisplatin therapy.

Implications for Nurses and Conclusion

Cisplatin is an integral component of chemotherapy regimens for multiple cancers, and nephrotoxicity remains the primary dose-limiting toxicity of this effective treatment. Hydration has been shown to maintain renal function and decrease nephrotoxicity in patients. In addition, magnesium supplementation has demonstrated nephroprotective effects in adults when included in hydration regimens before, during, and after cisplatin. Additional research is needed to evaluate outcomes of these interventions in the pediatric population.

Research does not currently support the administration of furosemide to prevent cisplatin-related nephrotoxicity in adults; however, mannitol may prevent nephrotoxicity. The use of mannitol in conjunction with magnesium was an independent factor in the protection of adults against nephrotoxicity induced by high-dose cisplatin (Muraki et al., 2012). Additional research is needed to evaluate these outcomes.

Nurses play a critical role in monitoring patients to prevent cisplatin-induced nephrotoxicity. The administration of hydration and the use of medications to aid in diuresis during cisplatin therapy is essential. Maintaining accurate weights and intake and outputs along with monitoring laboratory values and assessing for edema will help with early recognition of renal dysfunction. The provision of patient education focusing on nephrotoxicity prevention is an important component of the treatment regimen.

Although researchers have evaluated several supportive strategies to minimize nephrotoxicity in patients receiving cisplatin therapy, more research is needed. When more evidence is available, best nephroprotective practices can be developed and implemented. Until then, nurses should closely monitor kidney function in all patients receiving cisplatin and immediately report abnormalities to the healthcare team.

About the Author(s)

Elizabeth A. Duffy, DNP, RN, CPNP, is a clinical assistant professor in the School of Nursing at the University of Michigan in Ann Arbor; Wendy Fitzgerald, RN, MSN, PPCNP-BC, CPON®, is a pediatric nurse practitioner in the Center for Cancer and Blood Disorders at the Children’s National Medical Center in Washington, DC; Kelley Boyle, MSN, RN, PCNS-BC, is a pediatric BMT nurse coordinator at the University of California, San Francisco, Benioff Children’s Hospital; and Radha Rohatgi, PharmD, BCOP, is a hematology/oncology and bone marrow clinical pharmacy specialist at the Children’s National Medical Center. The authors take full responsibility for this content. This research was conducted by a team from the Children’s Oncology Group Nursing Evidence-Based Practice Subcommittee. The Children’s Oncology Group is supported by a National Cancer Institute/National Clinical Trials Network Group Operations Center grant (U10CA180886; principal investigator: Peter C. Adamson). Fitzgerald serves on a speakers bureau for United Therapeutics. During the writing of this article, Rohatgi served on a speakers bureau for the Pediatric Pharmacy Association. The article has been reviewed by independent peer reviewers to ensure that it is objective and free from bias. Duffy can be reached at eaduffy@med.umich.edu, with copy to CJONEditor@ons.org. (Submitted March 2017. Accepted June 19, 2017.)



Al Bahrani, B.J., Moylan, E.J., Forouzesh, B., Della-Fiorentina, S.A., & Goldrick, A.J. (2009). A short outpatient hydration schedule for cisplatin administration. Gulf Journal of Oncology, 5, 30–36.

Al-Sarraf, M., Fletcher, W., Oishi, N., Pugh, R., Hewlett, J.S., Balducci, L., . . . Padilla, F. (1982). Cisplatin hydration with and without mannitol diuresis in refractory disseminated malignant melanoma: A Southwest Oncology Group study. Cancer Treatment Reports, 66, 31–35.

Bellomo, R., Kellum, J.A., & Ronco, C. (2007). Defining and classifying acute renal failure: From advocacy to consensus and validation of the RIFLE criteria. Intensive Care Medicine, 33, 409–413. https://doi.org/10.1007/s00134-006-0478-x

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. European Journal of Cancer, 44, 2608–2614.

Dumas, M., de Gislain, C., d’Athis, P., Chadoint-Noudeau, V., Escousse, A., Guerrin, J., & Autissier, N. (1989). Evaluation of the effect of furosemide on ultrafilterable platinum kinetics in patients treated with cis-diamminedichloroplatinum. Cancer Chemotherapy and Pharmacology, 23, 37–40. https://doi.org/10.1007/BF00258455

Guyatt, G., Oxman, A.D., Akl, E.A., Kunz, R., Vist, G., Brozek, J., . . . Schünemann, H.J. (2011). GRADE guidelines: 1. Introduction—GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology, 64, 383–394. https://doi.org/10.1016/j.jclinepi.2010.04.026

Horinouchi, H., Kubota, K., Itani, H., Taniyama, T.K., Nakamichi, S., Wakui, H., . . . Tamura, I.S.T. (2013). Short hydration in chemotherapy containing cisplatin (≥ 75 mg/m2) for patients with lung cancer: A prospective study. Japanese Journal of Clinical Oncology, 43, 1105–1109.

Hotta, K., Takigawa, N., Hisamoto-Sato, A., Ichihara, E., Kudo, K., Uchida, K., . . . 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. Japanese Journal of Clinical Oncology, 43, 1115–1123.

Jones, D.P., Spunt, S.L., Green, D., & Springate, J.E. (2008). Renal late effects in patients treated for cancer in childhood: A report from the Children’s Oncology Group. Pediatric Blood and Cancer, 51, 724–731. https://doi.org/10.1002/pbc.21695

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

Launay-Vacher, V., Rey, J.-B., Isnard-Bagnis, C., Deray, G., & Daouphars, M. (2008). Prevention of cisplatin nephrotoxicity: State of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Cancer Chemotherapy and Pharmacology, 61, 903–909. https://doi.org/10.1007/s00280-008-0711-0

Lavolé, A., Danel, S., Baudrin, L., Gounant, V., Ruppert, A.M., Epaud, C., . . . Milleron, B. (2012). Routine administration of a single dose of cisplatin ≥ 75 mg/m2 after short hydration in an outpatient lung-cancer clinic. Bulletin du Cancer, 99, E43–E48.

Leu, L., & Baribeault, D. (2010). A comparison of the rates of cisplatin (cDDP)-induced nephrotoxicity associated with sodium loading or sodium loading with forced diuresis as a preventative measure. Journal of Oncology Pharmacy Practice, 16, 167–171. https://doi.org/10.1177/1078155209346071

McKibbin, T., Cheng, L.L., Kim, S., Steuer, C.E., Owonikoko, T.K., Khuri, F.R., . . . Saba, N.F. (2016). Mannitol to prevent cisplatin-induced nephrotoxicity in patients with squamous cell cancer of the head and neck (SCCHN) receiving concurrent therapy. Supportive Care in Cancer, 24, 1789–1793. https://doi.org/10.1007/s00520-015-2978-0

Melnyk, B.M., & Fineout-Overholt, E. (2015). Evidence-based practice in nursing and healthcare: A guide to best practice (3rd ed.). Philadelphia, PA: Lippincott Williams and Wilkins.

Miller, R.P., Tadagavadi, R.K., Ramesh, G., & Reeves, W.B. (2010). Mechanisms of cisplatin nephrotoxicity. Toxins, 2, 2490–2518. https://doi.org/10.3390/toxins2112490

Morgan, K.P., Snavely, A.C., Wind, L.S., Buie, L.W., Grilley-Olson, J., Walko, C.M., & Weiss, J. (2014). Rates of renal toxicity in cancer patients receiving cisplatin with and without mannitol. Annals of Pharmacotherapy, 48, 863–869. https://doi.org/10.1177/1060028014533303

Muraki, K., Koyama, R., Honma, Y., Yagishita, S., Shukuya, T., Ohashi, R., . . . Takahashi, K. (2012). Hydration with magnesium and mannitol without furosemide prevents the nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced non-small cell lung cancer. Journal of Thoracic Disease, 4, 562–568. https://doi.org/10.3978/j.issn.2072-1439.2012.10.16

Murray, A.W., Barnfield, M.C., Waller, M.L., Telford, T., & Peters, A.M. (2013). Assessment of glomerular filtration rate measurement with plasma sampling: A technical review. Journal of Nuclear Medicine Technology, 41, 67–75. https://doi.org/10.2967/jnmt.113.121004

National Cancer Institute. (2010). Common terminology criteria for adverse events [v.4.03]. Retrieved from http://bit.ly/2o2Zd4Y

Oka, T., Kimura, T., Suzumura, T., Yoshimoto, N., Nakai, T., Yamamoto, N., . . . Hirata, K. (2014). Magnesium supplementation and high volume hydration reduce the renal toxicity caused by cisplatin-based chemotherapy in patients with lung cancer: A toxicity study. BMC Pharmacology and Toxicology, 15, 70. https://doi.org/10.1186/2050-6511-15-70

Ostrow, S., Egorin, M.J., Hahn, D., Markus, S., Aisner, J., Chang, P., . . . Wiernik, P.H. (1981). High-dose cisplatin therapy using mannitol versus furosemide diuresis: Comparative pharmacokinetics and toxicity. Cancer Treatment Reports, 65, 73–78.

Ouchi, A., Asano, M., Aono, K., Watanabe, T., & Kato, T. (2014). Comparison of short and continuous hydration regimen in chemotherapy containing intermediate- to high-dose cisplatin. Journal of Oncology, 2014, 767652. https://doi.org/10.1155/2014/767652

Platania, M., Verzoni, E., & Vitali, M. (2015). Hyponatremia in cancer patients. Tumori, 101, 246–248. https://doi.org/10.5301/tj.5000257

Ruggiero, A., Rizzo, D., Trombatore, G., Maurizi, P., & Riccardi, R. (2016). The ability of mannitol to decrease cisplatin-induced nephrotoxicity in children: Real or not? Cancer Chemotherapy and Pharmacology, 77, 19–26. https://doi.org/10.1007/s00280-015-2913-6

Sakaida, E., Iwasawa, S., Kurimoto, R., Ebata, T., Imai, C., Oku, T., . . . Takiguchi, Y. (2016). Safety of a short hydration method for cisplatin administration in comparison with a conventional method—A retrospective study. Japanese Journal of Clinical Oncology, 46, 370–377. https://doi.org/10.1093/jjco/hyv203

Santoso, J.T., Lucci, J.A., 3rd, Coleman, R.L., Schafer, I., & Hannigan, E.V. (2003). Saline, mannitol, and furosemide hydration in acute cisplatin nephrotoxicity: A randomized trial. Cancer Chemotherapy and Pharmacology, 52, 13–18. https://doi.org/10.1007/s00280-003-0620-1

Skinner, R. (2011). Nephrotoxicity—What do we know and what don’t we know? Journal of Pediatric Hematology/Oncology, 33, 128–134. https://doi.org/10.1097/MPH.0b013e3181f8cac0

Skinner, R., Parry, A., Price, L., Cole, M., Craft, A.W., & Pearson, A.D.J. (2009). Persistent nephrotoxicity during 10-year follow-up after cisplatin or carboplatin treatment in childhood: Relevance of age and dose as risk factors. European Journal of Cancer, 45, 3213–3219. https://doi.org/10.1016/j.ejca.2009.06.032

Stevens, L.A., Coresh, J., Greene, T., & Levey, A.S. (2006). Assessing kidney function—Measured and estimated glomerular filtration rate. New England Journal of Medicine, 354, 2473–2483. https://doi.org/10.1056/NEJMra054415

Tiseo, M., Martelli, O., Mancuso, A., Sormani, M.P., Bruzzi, P., Di Salvia, R., . . . Ardizzoni, A. (2007). Short hydration regimen and nephrotoxicity of intermediate to high-dose cisplatin-based chemotherapy for outpatient treatment in lung cancer and mesothelioma. Tumori, 93, 138–144.

Vogl, S.E., Zaravinos, T., Kaplan, B.H., & Wollner, D. (1981). Safe and effective two-hour outpatient regimen of hydration and diuresis for the administration of cis-diamminedichloroplatinum (II). European Journal of Cancer, 17, 345–350.

Willox, J.C., McAllister, E.J., Sangster, G., & Kaye, S.B. (1986). Effects of magnesium supplementation in testicular cancer patients receiving cis-platin: A randomised trial. British Journal of Cancer, 54, 19–23.

Womer, R.B., Pritchard, J., & Barratt, T.M. (1985). Renal toxicity of cisplatin in children. Journal of Pediatrics, 106, 659–663.

Yamamoto, Y., Watanabe, K., Tsukiyama, I., Matsushita, H., Yabushita, H., Matsuura, K., & Wakatsuki, A. (2015). Nephroprotective effects of hydration with magnesium in patients with cervical cancer receiving cisplatin. Anticancer Research, 35, 2199–2204.

Yoshida, T., Niho, S., Toda, M., Goto, K., Yoh, K., Umemura, S., . . . Ohe, Y. (2014). Protective effect of magnesium preloading on cisplatin-induced nephrotoxicity: A retrospective study. Japanese Journal of Clinical Oncology, 44, 346–354. https://doi.org/10.1093/jjco/hyu004

Zareifar, S., Jafari, H., Geramizadeh, B., Basiratnia, M., Golafshan, H., Cohan, N., . . . Hamidi, R. (2013). The evaluation of cisplatin effect on tubular function in children on chemotherapy. Pediatric Hematology and Oncology, 30, 18–24. https://doi.org/10.3109/08880018.2012.737093