Department of Nephrology-Dialysis-Transplantation, Centre Hospitalier Universitaire de Nice, Nice, France.
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.
Cancer Immunol Immunother. 2021 Nov;70(11):3357-3364. doi: 10.1007/s00262-021-02983-8. Epub 2021 Jun 21.
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.
免疫检查点抑制剂(ICIs)旨在促进针对癌症的免疫反应,已被证明在几种晚期恶性肿瘤中有效,但也会引起免疫相关的不良反应,影响多个器官,尤其是肾脏。在此,对迄今为止向法国药物警戒数据库报告的所有经活检证实的免疫检查点抑制剂相关肾病病例进行了回顾性描述性分析。收集了患者特征、急性肾损伤和组织病理学特征的数据。共纳入 63 例经活检证实的病例进行分析。免疫相关性肾病在引入 ICI 后平均 105.5±98.6(标准差)天发生。肾脏疾病:改善全球预后急性肾损伤 3 期发生在 36.5%的患者中,平均峰值血清肌酐为 288µmol/L。组织病理学提示 52 例(83%)患者为急性肾小管间质性肾炎,18 例(29%)存在急性肾小管坏死,其中 5 例(8%)存在肾小球受累。25 例(39.7%)患者还记录到另一种免疫相关不良事件。88.9%的患者接受了皮质类固醇治疗。总体而言,27.0%的患者完全恢复,54.0%的患者部分恢复,12.7%的患者未恢复。19 例患者尝试再次用药,1 例患者复发。四分之三的患者使用了已知会引起急性肾小管间质性肾炎的药物。该研究的主要局限性在于药物警戒研究固有的局限性,如回顾性和数据不完整。尽管它不能得出任何病理生理学结论,但本研究描述了在一个大的严重程度不一的活检患者队列中,免疫检查点抑制剂相关肾病的临床和组织病理学特征。