| アブストラクト | Background: Immune checkpoint inhibitors (ICIs) foster anti-cancer immune responses. Their efficacy comes at the cost of immune-related adverse events (IRAEs). The latter affects various organs, including kidneys, mostly as acute tubulointerstitial nephritis, the pathophysiology of which remains unclear. We conducted a multicentre case-control study to compare the characteristics of patients with renal IRAEs (ICI-AKI) with those of patients diagnosed with other IRAEs. Methods: We queried the French pharmacovigilance database for all adverse events involving ICIs. Reports were classified as ICI-AKI or extrarenal IRAE. For each ICI-AKI report, four reports of extrarenal IRAEs were randomly included (control group, 4:1 ratio). Variables showing an association with a P < 0.05 were included as covariates in a multivariate analysis. Results: Therefore, 167 ICI-AKI reports were compared with 668 extrarenal IRAEs. At least one concomitant extrarenal IRAE was mentioned in 44.3% of ICI-AKI reports. Patients with ICI-AKI were significantly older than patients with extrarenal IRAEs (69.1 versus 64.6 years; P = 0.0135), and chronic kidney disease was significantly more prevalent (12.0% versus 3.3%; P = 0.0125). Patients with ICI-AKI were significantly more likely to be treated with fluindione [adjusted odds ratio (OR) 6.53, 95% confidence interval (95% CI) 2.21-19.31; P = 0.0007], a non-steroidal anti-inflammatory drug (NSAID, OR 3.18, 95% CI 1.07-9.4; P = 0.0368) or a proton-pump inhibitor (PPI, OR 2.18, 95% CI 1.42-3.34; P = 0.0004). Conclusion: This study is limited by a lack of data, preventing confirmation of numerous reports therefore not included in the analysis. We are unable to draw definite pathophysiological conclusions from our data. Nonetheless, we suggest that ICIs may be a 'second-hit' that precipitates acute kidney injury caused by another concomitant drug (fluindione, NSAID or PPI). |
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| ジャーナル名 | Clinical kidney journal |
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| 投稿日 | 2022/9/27 |
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| 投稿者 | Gerard, Alexandre O; Barbosa, Susana; Parassol, Nadege; Andreani, Marine; Merino, Diane; Cremoni, Marion; Laurain, Audrey; Pinel, Sylvine; Bourneau-Martin, Delphine; Rocher, Fanny; Esnault, Vincent L M; Borchiellini, Delphine; Sicard, Antoine; Drici, Milou-Daniel |
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| 組織名 | Department of Nephrology-Dialysis-Transplantation, University Hospital Centre of;Nice, Nice, France.;Department of Pharmacology and Pharmacovigilance Centre of Nice, University;Hospital Centre of Nice, Nice, France.;Institute of Molecular and Cellular Pharmacology (IPMC), UMR 7275, CNRS,;University Cote d'Azur, Valbonne, France.;Pharmacovigilance Center of Paris-Fernand Widal, Assistance Publique-Hopitaux de;Paris, Paris, France.;Pharmacovigilance Center of Angers, University Hospital Centre of Angers, Angers,;France.;Department of Medical Oncology, Centre Antoine Lacassagne, University Cote;d'Azur, Nice, France.;Laboratory of Molecular Physio Medicine (LP2M), UMR 7370, CNRS, University Cote;Clinical Research Unit of University Cote d'Azur (UR2CA), University Cote d'Azur,;Nice, France. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/36158153/ |
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