Immune checkpoint inhibitors-induced nephropathy: a French national survey

Cancer Immunol Immunother. 2021 Nov;70(11):3357-3364. doi: 10.1007/s00262-021-02983-8. Epub 2021 Jun 21.

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.

Keywords: Acute kidney injury; Histopathology; Immune checkpoint inhibitors; Immunotherapy; Nephrology; Pharmacovigilance.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / pathology*
  • Adult
  • Aged
  • Female
  • France
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Surveys and Questionnaires

Substances

  • Immune Checkpoint Inhibitors