Rao Ullur Avinash, Côté Gabrielle, Pelletier Karyne, Kitchlu Abhijat
Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Canada.
Division of Nephrology, Department of Medicine, CHU de Québec, Université Laval, Quebec City, Canada.
Clin Kidney J. 2023 Jan 28;16(6):939-951. doi: 10.1093/ckj/sfad014. eCollection 2023 Jun.
Immune checkpoint inhibitors (ICI) are now widely used in the treatment of many cancers, and currently represent the standard of care for multiple malignancies. These agents enhance the T cell immune response to target cancer tissues, and have demonstrated considerable benefits for cancer outcomes. However, despite these improved outcomes, there are important kidney immune-related adverse events (iRAEs) associated with ICI. Acute tubulo-interstitial nephritis remains the most frequent kidney iRAE, however glomerular lesions and electrolytes disturbances are increasingly being recognized and reported. In this review, we summarize clinical features and identify risk factors for kidney iRAEs, and discuss the current understanding of pathophysiologic mechanisms. We highlight the evidence basis for guideline-recommended management of ICI-related kidney injury as well as gaps in current knowledge. We advocate for judicious use of kidney biopsy to identify ICI-associated kidney injury, and early use of corticosteroid treatment where appropriate. Selected patients may also be candidates for re-challenge with ICI therapy after a kidney iRAE, in view of current data on recurrent rates of kidney injury. Risk of benefits of re-challenge must be considered on an individual considering patient preferences and prognosis. Lastly, we review current knowledge of ICI use in the setting of patients with end-stage kidney disease, including kidney transplant recipients and those receiving dialysis, which suggest that these patients should not be summarily excluded from the potential benefits of these cancer therapies.
免疫检查点抑制剂（ICI）目前广泛应用于多种癌症的治疗，是多种恶性肿瘤的标准治疗方法。这些药物可增强T细胞对靶癌组织的免疫反应，并已证明对癌症治疗效果有显著益处。然而，尽管治疗效果有所改善，但ICI仍会引发重要的肾脏免疫相关不良事件（iRAE）。急性肾小管间质性肾炎仍然是最常见的肾脏iRAE，不过肾小球病变和电解质紊乱也越来越多地被认识和报道。在本综述中，我们总结了肾脏iRAE的临床特征，确定了其危险因素，并讨论了目前对病理生理机制的认识。我们强调了指南推荐的ICI相关肾损伤管理的证据基础以及当前知识的空白。我们主张谨慎使用肾活检来识别ICI相关的肾损伤，并在适当情况下尽早使用皮质类固醇治疗。鉴于目前关于肾损伤复发率的数据，部分患者在发生肾脏iRAE后也可能适合重新接受ICI治疗。在考虑患者偏好和预后的情况下，必须对重新挑战的风险和益处进行个体化评估。最后，我们回顾了目前关于终末期肾病患者（包括肾移植受者和接受透析的患者）使用ICI的知识，这表明不应将这些患者一概排除在这些癌症治疗的潜在益处之外。
