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Immune checkpoint inhibitors-induced nephropathy: a French national survey
Alexandre O Gérard1,2, Marine Andreani1, Audrey Fresse2
1Department of Nephrology-Dialysis-Transplantation, Centre Hospitalier Universitaire de Nice, Nice, France.
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.
Insights
Immune checkpoint inhibitors (ICIs) can cause kidney damage, with most cases showing acute tubule-interstitial nephritis. While corticosteroids helped many patients, a significant portion experienced partial or no recovery from ICI-induced nephropathy.
Area of Science:
- Nephrology
- Oncology
- Immunology
Background:
- Immune checkpoint inhibitors (ICIs) enhance anti-cancer immunity but can cause immune-related adverse events, including kidney damage.
- ICI-induced nephropathy presents a significant clinical challenge, necessitating a deeper understanding of its characteristics.
Purpose of the Study:
- To analyze clinical and histopathological features of biopsy-proven ICI-induced nephropathy.
- To describe patient outcomes and treatment responses in ICI-induced kidney injury.
Main Methods:
- Retrospective analysis of biopsy-confirmed ICI-induced nephropathy cases from the French Pharmacovigilance database.
- Data collection included patient demographics, acute kidney injury (AKI) severity, and histopathological findings.
Main Results:
- 63 cases of ICI-induced nephropathy were analyzed, with a mean onset of 105.5 days post-ICI initiation.
- Acute tubule-interstitial nephritis was the predominant histopathological finding (83%), with 36.5% of patients experiencing AKI stage 3.
- Corticosteroid treatment was administered in 88.9% of cases, leading to full recovery in 27.0% and partial recovery in 54.0%.
Conclusions:
- ICI-induced nephropathy is characterized mainly by acute tubule-interstitial nephritis.
- While corticosteroids are a common treatment, recovery rates vary, highlighting the need for further research into optimal management strategies.
- This study provides valuable insights into the clinical spectrum and outcomes of ICI-induced kidney injury in a large cohort.
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