Evaluation of Cisplatin-Induced Acute Kidney Injury in Patients Coprescribed Serotonin Receptor Antagonists: A Retrospective Analysis

Abstract

Key Points Serotonin receptor antagonists reduce the incidence of AKI in patients receiving cisplatin as chemotherapy.New-generation serotonin receptors do not offer any additional advantage in terms of protection from cisplatin induced AKI. Background Cisplatin is an effective first-line therapy for a variety of cancers. Cisplatin is highly emetogenic and resulting volume depletion can contribute to AKI. Antiemetic drugs, such as 5-hydroxytryptamine type 3 receptor antagonists (5-HT3RAs), are commonly prescribed to prevent this complication. Preclinical studies suggest first-generation 5-HT3RAs may alter the renal clearance and increase cisplatin toxicity. This retrospective study evaluated whether different 5-HT3RAs modify the risk of AKI in patients receiving cisplatin. Methods Patients with cancer who received cisplatin between January 1, 2010, and December 31, 2016, were included. Patients older than 18 years with available data for baseline and post-treatment serum creatinine, cisplatin cumulative dose, and administration of 5-HT3RAs, including first-generation (ondansetron, granisetron, and ramosetron) and second-generation (palonosetron), were analyzed. AKI was defined as 1.5× increase in serum creatinine. Fisher exact and Wilcoxon rank-sum tests were used to assess univariable associations between baseline covariates and AKI and logistic regression for multivariable associations with AKI. Results Of 8703 patients identified with cisplatin exposure, 6889 were included. A total of 3881 patients (56.3%) received at least one 5-HT3RA, including palonosetron (3750, 54.4%), ondansetron (1399, 20.3%), and granisetron (11, 0.2%). AKI developed in 1666 patients (24.2%) after cisplatin therapy. Patients who received any 5-HT3RAs were less likely to experience AKI as compared with patients who did not (22.6% versus 26.2%, P = 0.001). Older age, male sex, African ethnicity, and cumulative cisplatin dose were univariably associated with higher risk of AKI (P < 0.001). After adjusting for these variables, use of any of these antiemetic drugs was protective for AKI (odds ratio, 0.84; 95% confidence interval, 0.75 to 0.94; P = 0.003) with no difference detected between type of 5-HT3RA. Conclusions Nephrotoxicity continues to be a concern after cisplatin therapy. Given its emetogenic nature, use of antiemetic drugs, such as 5-HT3RAs, can lessen emesis and lower risk of kidney injury. This retrospective analysis supports use of any 5-HT3RAs to lower risk of AKI.