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Cancer Chemotherapy and Pharmacology

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01-11-2020 | Acute Kidney Injury | Original Article

Assessment of acute kidney injury related to small-molecule protein kinase inhibitors using the FDA adverse event reporting system

Authors: Qianqian Fan, Jie Ma, Bo Zhang, Qiuyue Li, Fang Liu, Bin Zhao

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2020

Abstract

Purpose

Small-molecule protein kinase inhibitors (PKIs) have substantially improved clinical outcomes of various diseases. However, some studies suggested these agents might induce acute kidney injury (AKI). This study was designed to comprehensively assess the adverse events of AKI in real-world patients receiving small-molecule PKIs using the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Methods

The FAERS data between 2004 and 2019 were extracted to describe the characteristics of AKI cases after the use of small-molecule PKIs approved by the FDA. The reporting odds ratio (ROR) with 95% confidence interval (CI) for AKI was calculated for each small-molecule PKI agent. A disproportionality signal was defined when the lower limit of 95% CI > 1.

Results

Among the 462,020 adverse event reports for small-molecule PKIs, 9970 (2.16%) were identified as AKI cases. The median AKI onset time was 32 (interquartile range 11–124) days after the initiation of small-molecule PKI treatment. A total of 61.38% and 26.04% of AKI cases resulted in hospitalization and death, respectively. Based on RORs, 14 of 52 small-molecule PKIs yielded disproportionality signals for AKI, including six VEGFR inhibitors, three mTOR inhibitors and five small-molecule PKIs with other targets. The agents with the highest AKI RORs were entrectinib (ROR 6.40, 95% CI 2.23, 18.34), sirolimus (ROR 3.76, 95% CI 3.45, 4.09), and cobimetinib (ROR 3.40, 95% CI 2.69, 4.28).

Conclusion

Analysis of the FAERS data helped identify the small-molecule PKIs that were most frequently reported for AKI. Further investigations are needed to confirm these potential risks.

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Title: Assessment of acute kidney injury related to small-molecule protein kinase inhibitors using the FDA adverse event reporting system
Authors: Qianqian Fan
Jie Ma
Bo Zhang
Qiuyue Li
Fang Liu
Bin Zhao
Publication date: 01-11-2020
Publisher: Springer Berlin Heidelberg
Keywords: Acute Kidney Injury
Acute Kidney Injury
Entrectinib
mTOR-Inhibitors
Published in: Cancer Chemotherapy and Pharmacology / Issue 5/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04151-8

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