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

Key Points:

1. Serotonin receptor antagonists reduce the incidence of AKI in patients receiving cisplatin as chemotherapy.

2. 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.