Risk Factors for Cisplatin-Induced Nephrotoxicity: A Multicenter Retrospective Study

Abstract

<b><i>Introduction:</i></b> Cisplatin (CDDP)-induced nephrotoxicity is a concern in CDDP-based chemotherapy. The goal of this multicenter retrospective study was to identify potential risk factors for CDDP nephrotoxicity. <b><i>Methods:</i></b> Clinical data were reviewed for 762 patients who underwent chemotherapy including CDDP ≥60 mg/m<sup>2</sup> per day from Spring 2014 to September 2016. CDDP nephrotoxicity was defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events for acute kidney injury. Univariate and multivariate logistic regression analyses were performed to identify risk factors for CDDP nephrotoxicity. <b><i>Results:</i></b> CDDP nephrotoxicity was observed in 165 patients (21.7%). Multivariate analysis showed a significantly higher rate of CDDP nephrotoxicity in patients with cardiac disease (odds ratio [OR]: 2.05, 95% confidence interval [CI]: 1.07–3.93, <i>p</i> = 0.03), hypertension (OR: 1.57, 95% CI: 1.06–2.32, <i>p</i> = 0.02), and high-dose CDDP therapy (OR: 2.15, 95% CI: 1.50–3.07, <i>p</i> < 0.01). Magnesium (Mg) supplementation (OR: 0.65, 95% CI: 0.45–0.93, <i>p</i> = 0.02) and diuretic use (OR: 0.22, 95% CI: 0.08–0.63, <i>p</i> < 0.01) were also independent risk factors for CDDP nephrotoxicity. <b><i>Conclusions:</i></b> Our results suggest that high-dose CDDP and comorbidities of cardiac disease and hypertension are independent risk factors for CDDP nephrotoxicity. Therefore, close monitoring of serum creatinine values during CDDP treatment is recommended for patients with these risk factors. In addition, Mg supplementation and administration of diuretics might be effective for prevention of CDDP nephrotoxicity.

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

“…The study design, including patient enrollment, data collection, and treatment, was described previously [20]. In brief, this multicenter, retrospective, observational study was conducted from spring 2014 to September 2016 in ve hospitals a liated with the National Hospital Organization in Kyushu, Japan.…”

“…Mg supplementation should be kept to a necessity minimum, as there is concern that renal dysfunction may lead to hypermagnesemia. In our previous study reporting the risk factors for CDDP-induced nephrotoxicity [20], cardiac disease, hypoalbuminemia, non-Mg supplementation, hypertension, and high dose CDDP were extracted as risk factors.…”

“…Therefore, in this study, we investigated whether 20 mEq of Mg supplementation is more effective than 8 mEq of Mg in preventing CDDP-induced nephrotoxicity, as well as the associated risk factors, in cancer patients treated with CDDP-based chemotherapy, based on a pooled dataset of our previous study [20].…”

Preloading magnesium attenuates cisplatin-associated nephrotoxicity: pilot randomized controlled trial (PRAGMATIC study)

“…A review of studies reporting on nephrotoxicity with standard high-dose cisplatin has led to clinical practice guidelines recommending that 8-20 mEq of magnesium should be administered intravenously prior to standard high-dose cisplatin administration. 1 , 3 , 17 , 18 , 19 Minzi et al. 17 reported that 8 mEq of intravenous magnesium decreased the incidence of nephrotoxicity without serious side-effects.…”

Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells

“…Cisplatin (CIS) is a common first-line chemotherapy drug in treating esophageal cancer [ 7 ]; however, its application is limited by drug resistance and dose-related side effects [ 8 , 9 ]. A higher dose, either cumulative dose or doses per treatment, result in irreversible kidney injury [ 10 ]. Therefore, combining CIS with another drug can be beneficial, such that the synergistic effects will enhance treatment efficacy, and lower CIS dosage will reduce its side effects.…”