免疫检查点抑制剂致急性肾损伤的研究进展

Research progress of immune checkpoint inhibitor-induced acute kidney injury

免疫检查点抑制剂(ICPi)是一种靶向作用于表达在T细胞表面的免疫抑制分子的单克隆抗体,其作为一种新兴的免疫治疗药物,已广泛用于治疗各种实体肿瘤和血液系统肿瘤。然而,ICPi也导致了一类新的自体免疫相关不良反应的发生,一般称之为免疫治疗相关不良反应(irAEs)。急性肾损伤(AKI)为ICPi常见的irAEs之一,本文就ICPi诱发AKI的临床表现、发生率、危险因素、发生机制及相关治疗等内容进行综述。ICPi致AKI的风险明显高于化疗药物,其发生的危险因素涉及ICPi药物种类和联用质子泵抑制剂(PPIs)。ICPi所致AKI最常见的临床表现为血清肌酐升高和脓尿,典型的组织病理学特征为急性肾小管间质性肾炎(ATIN)。在使用ICPi治疗期间应密切监测肾功能,以便早期发现及干预AKI,治疗以糖皮质激素治疗为主,必要时可加用免疫抑制类药物。本研究可为我国ICPi的临床安全应用提供参考,以期改善肿瘤患者预后,使其更大程度获益。

Immune checkpoint inhibitors(ICPis),a kind of monoclonal antibodies that target inhibitory receptors expressed on T cells,represent an emerging class of immunotherapy used in treating solid organ and hematologic malignancies.Unfortunately,ICPis have also been associated with the emergence of a new subsets of autoimmune-like toxicities,known as immune-related adverse events(irAEs).Acute kidney injury(AKI)is one of the common irAEs.This paper reviews the clinical manifestations,incidence,risk factors,mechanisms and treatment of ICPi-induced AKI.The risk of ICPi-induced AKI is significantly higher than that induced by chemotherapeutic drugs,and the involved risk factors include the type of ICPi drug and the proton pump inhibitors(PPIs).The typical symptom of ICPi-induced AKI is increased serum levels of creatinine and pyuria.The typical histopathological features are acute tubulointerstitial nephritis(ATIN).During ICPi treatment,renal function should be closely monitored to detect and intervene AKI early.The main treatment is glucocorticoid therapy,and immunosuppressive drugs can be added when necessary.This study provides reference for the clinical safety application of ICPi in China with a view to improve the prognosis of cancer patients and make them more beneficial.