Kidney Week

Abstract: PUB024

Effects of 5-HT3A Antiemetic Drugs on Cisplatin-Induced Nephrotoxicity

Session Information

• Publication Only

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Shingarev, Roman A., Memorial Sloan Kettering Cancer Center, New York, New York, United States

Roman A. Shingarev,

• Latcha, Sheron, Memorial Sloan Kettering Cancer Center, New York, New York, United States

Sheron Latcha,

• Jaimes, Edgar A., Memorial Sloan Kettering Cancer Center, New York, New York, United States

Edgar A. Jaimes,

Background

Cisplatin is an important component of chemotherapy for patients with lung, head and neck, and cervical cancer that induces cellular apoptosis by forming intrastrand DNA crosslinks that prevent DNA transcription. While desirable for malignant cells, cisplatin cytotoxicity in renal cortex leads to AKI. Tubular epithelial cell exposure to cisplatin is determined by its transport via organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1). MATE1 is inhibited by 5-hydroxytryptamine-3 receptor antagonists (5-HT3 RA) commonly used as antiemetics in oncology. Our data indicates that ondansetron use in mice results in greater GFR loss relative to other 5-HT3 RA. We sought to examine the association of 5-HT3 RA use in patients receiving cisplatin with AKI.

Methods

In retrospective chart review, we identified 7,094 patients who received cisplatin, of which 3,997 (56.3%) were treated with a 5-HT3 RA that included either granisetron, ondansetron or palonosetron. Fisher's exact test tested for univariable associations between categorical variables. Multivariable associations with AKI were analyzed using logistic regression.

Results

Ondansetron accounted for 27% of overall 5-HT3 RA use. AKI was observed in 1,737 or 24.5% of patients receiving cisplatin. 5-HT3 RA use was independently associated with lower risk of AKI (OR 0.38; 95% CI, 0.23-0.65, p< 0.001). Other significant multivariable associations with AKI are found in Table.

Conclusion

Protective effect of 5-HT3 RA use in humans, contrary to our animal model, is likely accounted for by lesser inhibition of MATE1 by the most commonly used palonosetron. Increased risk of cisplatin-induced tubular toxicity in this scenario is likely further offset by the lower risk of pre-renal AKI from vomiting and anorexia, incited by cisplatin. Effects of the individual 5-HT3 RA on renal outcomes are the subject of active investigation.