RESUMO
BACKGROUND: Cisplatin is an effective first line therapy for a variety of cancers. Cisplatin is highly emetogenic and resulting volume depletion can contribute to acute kidney injury (AKI). Anti-emetic 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 over 18 years old 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 defined as 1.5x increase in serum creatinine. Fisher's 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 (56.3%) patients received at least one 5-HT3RA, including palonosetron (3750, 54.4%), ondansetron (1399, 20.3%) and granisetron (11, 0.2%). AKI developed in 1666 (24.2%) patients following cisplatin. Patients who received any 5-HT3RAs were less likely to experience AKI as compared to patients that did not (22.6% vs 26.2%, p=0.001). Older age, male gender, African ethnicity, and cumulative cisplatin dose were univariately associated with higher risk for AKI (P<0.001). After adjusting for these variables, use of any of these antiemetic drugs was protective for AKI (OR 0.84, 95% CI: 0.75, 0.94; P= 0.003) with no difference detected between type of 5-HT3RA. CONCLUSION: Nephrotoxicity continues to be a concern following 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.
