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Immune checkpoint inhibitors-induced nephropathy: a French national survey

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Abstract

Immune checkpoint inhibitors (ICIs), aiming to foster cancer-targeted immune response, proved to be effective in several advanced malignancies at the price of immune-related adverse events affecting various organs, notably the kidneys. Herein, a retrospective descriptive analysis was performed on all biopsy-confirmed cases of ICI-induced nephropathy notified to the French Pharmacovigilance database to date. Data were gathered about patients’ characteristics, acute kidney injuries and histopathological features. A total of 63 biopsy-proven cases were included for analysis. Immune-related nephropathy occurred after a mean of 105.5 ± 98.6 (standard deviation) days after the introduction of the ICI. Kidney Disease: Improving Global Outcomes acute kidney injury stage 3 occurred in 36.5% of patients, and the mean peak serum creatinine was 288 µmol/L. Histopathology suggested acute tubule-interstitial nephritis in 52 patients (83%), while signs of acute tubular necrosis were found in 18 (29%) and glomerular involvement in 5 of them (8%). Another immune-related adverse event was documented in 25 patients (39.7%). Patients were treated with corticosteroids in 88.9% of cases. All in all, 27.0% fully recovered, 54.0% partially recovered, 12.7% did not recover. Rechallenge was attempted in 19 patients and one patient relapsed. Three-quarters of patients received a medication known to cause acute tubule-interstitial nephritis. The major limits of this study are those inherent to pharmacovigilance studies, such as its retrospective nature and incomplete data. Although it cannot pretend drawing any pathophysiological conclusion, this study depicts the clinical and histopathological pictures of ICI-induced nephropathies in a large cohort of biopsied patients with all grades of severity.

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Availability of data and materials

The French Pharmacovigilance Database (PVD) has been approved by the National Data Protection Agency (CNIL). All our data originate from this database. In accordance with European regulation, this retrospective observational study of anonymous reports did not need the approval of an Institutional Review Board/Independent Ethics Committee. This research was allowed by the Pharmacovigilance network which was kept informed.

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Acknowledgements

The authors thank Elise VAN OBBERGHEN (MD) and Ellen VAN OBBERGHEN-SCHILLING (PhD), both native speakers of American English, for proofreading and useful comments. They received no compensation for this work.

Funding

The authors do declare there is no source of funding for this study.

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Author notes

  1. Marine Andreani and Audrey Fresse have contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology-Dialysis-Transplantation, Centre Hospitalier Universitaire de Nice, Nice, France

    Alexandre O. Gérard, Marine Andreani & Vincent L. M. Esnault

  2. Department of Pharmacology and Pharmacovigilance, Pasteur Hospital Center of Nice, Centre Hospitalier Universitaire de Nice, Bât J4, 30 Avenue de la Voie Romaine - CS51069, 06001, Nice Cedex 01, France

    Alexandre O. Gérard, Audrey Fresse, Nadège Parassol, Fanny Rocher & Milou-Daniel Drici

  3. Department of Allergology, Centre Hospitalier Universitaire de Nice, Nice, France

    Marine Muzzone

  4. Pharmacovigilance Center of Paris - Fernand Widal, Assistance Publique - Hôpitaux de Paris, Paris, France

    Sylvine Pinel

  5. Pharmacovigilance Center of Angers, Centre Hospitalier Universitaire d’Angers, Angers, France

    Delphine Bourneau-Martin

  6. Department of Medical Oncology, Centre Antoine Lacassagne, Université Côte d’Azur, Nice, France

    Delphine Borchiellini

Authors
  1. Alexandre O. Gérard
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  2. Marine Andreani
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  10. Vincent L. M. Esnault
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  11. Milou-Daniel Drici
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the French Network of Pharmacovigilance Centers

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All authors read and approved the final version of the manuscript.

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Correspondence to Milou-Daniel Drici.

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Précis: The various patterns of nephropathies associated with immune checkpoint inhibitors remain unclear. We analyzed the French Pharmacovigilance Database to provide insight on their clinical and histopathological characteristics.

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Gérard, A.O., Andreani, M., Fresse, A. et al. Immune checkpoint inhibitors-induced nephropathy: a French national survey. Cancer Immunol Immunother 70, 3357–3364 (2021). https://doi.org/10.1007/s00262-021-02983-8

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  • DOI: https://doi.org/10.1007/s00262-021-02983-8

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