Characterizing the Real-World Risks of Kidney Injuries Associated with Chimeric Antigen Receptor T Cell Therapies—Evidence and Safety

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Abstract
Background: Recently, several cutting-edge experimental studies have directed chimeric antigen receptor (CAR)-T therapies toward specific renal diseases, revealing substantial renal benefits. Prior to widespread implementation of these animal experiments and potentially clinical trials, it is crucial to assess the renal safety of CAR-T therapies using real-world safety evidence. Methods: Our focus was on utilizing 4 algorithms, including disproportionality analysis, based on the US Food and Drug Administration Adverse Event Reporting System database, to filter positive signals of acute and chronic renal injury associated with 6 CAR-T therapies. Further determination of causality was achieved through Mendelian randomization (MR) for drugs associated with renal injury events showing a correlation. Results: Six therapies were evaluated involving a total of 9,770 patients, with only acute kidney injury (AKI) identified as associated with idecabtagene vicleucel treatment using 4 algorithmic thresholds, including disproportionality analysis. Subsequently, MR revealed no causal relationship between the idecabtagene vicleucel target B cell maturation antigen and the risk of AKI ( P = 0.576), a finding validated in another independent dataset ( P = 0.734). Conclusion: CAR-T therapies do not directly cause renal damage and necessitate controlling adverse renal risks during or after treatment, such as cytokine release syndrome. Future research efforts should rigorously optimize these aspects to better cater to nephrologists’ requirements.
Funding Information
  • National Natural Science Foundation of China (82470736, 22321005)
  • National Natural Science Foundation of China (82170711, 82070733)
  • National Aerospace Science Foundation of China (824B2015)

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