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. 2020 Nov;86(5):655-662.
doi: 10.1007/s00280-020-04151-8. Epub 2020 Oct 1.

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

Qianqian Fan  1 , Jie Ma  2 , Bo Zhang  1 , Qiuyue Li  1 , Fang Liu  1 , Bin Zhao  3
Affiliations

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

Qianqian Fan et al. Cancer Chemother Pharmacol. 2020 Nov.

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.

Keywords: Acute kidney injury; Adverse event; FAERS; Real-world data; Reporting odds ratio; Small-molecule protein kinase inhibitors.

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References

    1. Food and Drug Administration. Drugs@FDA: FDA-Approved Drugs. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm . Accessed 22 Aug 2020
    1. Roskoski R Jr (2020) Properties of FDA-approved small molecule protein kinase inhibitors: a 2020 update. Pharmacol Res 152:104609. https://doi.org/10.1016/j.phrs.2019.104609 - DOI
    1. Porta C, Cosmai L, Gallieni M, Pedrazzoli P, Malberti F (2015) Renal effects of targeted anticancer therapies. Nat Rev Nephrol 11(6):354–370. https://doi.org/10.1038/nrneph.2015.15 - DOI
    1. Goldstein SL (2016) Medication-induced acute kidney injury. Curr Opin Crit Care 22(6):542–545. https://doi.org/10.1097/MCC.0000000000000355 - DOI
    1. Yilmaz M, Lahoti A, O'Brien S, Nogueras-Gonzalez GM, Burger J, Ferrajoli A, Borthakur G, Ravandi F, Pierce S, Jabbour E, Kantarjian H, Cortes JE (2015) Estimated glomerular filtration rate changes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. Cancer 121(21):3894–3904. https://doi.org/10.1002/cncr.29587 - DOI - PMC

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