Division of Internal Medicine, Section of Nephrology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Institute of Academic Medicine and Weill Cornell Medical College, Houston Methodist Cancer Center, Houston, Texas, USA.
J Immunother Cancer. 2020 Jul;8(2). doi: 10.1136/jitc-2020-000750.
The percentage of patients with cancer eligible for checkpoint inhibitor (CPI) therapy has increased rapidly over the past few years and approaches 45%. As a result, more cases of CPI-related nephrotoxicity, including a rare subset with vasculitis, are being reported. To elucidate the clinical presentation of CPI-associated renal vasculitis and its possible mechanisms, treatment options and prognosis, we describe cases from a comprehensive cancer center and reviewed the literature for similar cases. We retrospectively reviewed the charts of all patients with cancer from 2014 to 2020 who were diagnosed with CPI-related nephrotoxicity and underwent a kidney biopsy. We identified five cases of renal vasculitis: three patients were diagnosed with seronegative antineutrophil cytoplasm antibody (ANCA)-associated vasculitis, one case with seropositive ANCA-associated vasculitis and one case was diagnosed with IgA vasculitis. Of these cases, four patients were receiving nivolumab, and one patient was receiving tremelimumab. All patients had microscopic hematuria, four out of five patients had negative ANCA serology, one patient had concurrent lung involvement and positive ANCA serology, and all had severe acute kidney injury with creatinine >4.50 mg/dL on diagnosis. All patients were treated by discontinuing CPI and initiating corticosteroids and rituximab. Three patients received plasmapheresis; two of these required renal replacement therapy including the patient with lung involvement. All patients after rituximab had a partial or complete renal response. Two patients died within 8 months of diagnosis due to malignancy progression. None of the patients had a relapse of vasculitis. We demonstrated that CPI can be associated with different types of renal vasculitis that are predominantly ANCA negative and manifest as severe acute kidney injury. Despite the lack of strong evidence, treatment similar to treatment of primary seropositive ANCA-associated vasculitis with corticosteroids and rituximab is well tolerated with favorable renal outcomes.
在过去的几年中，适合接受检查点抑制剂 (CPI) 治疗的癌症患者比例迅速增加，接近 45%。因此，越来越多的 CPI 相关肾毒性病例被报道，包括一组罕见的血管炎病例。为了阐明 CPI 相关肾血管炎的临床表现及其可能的机制、治疗选择和预后，我们描述了来自一个综合性癌症中心的病例，并回顾了类似病例的文献。我们回顾性分析了 2014 年至 2020 年间所有被诊断为 CPI 相关肾毒性并接受肾活检的癌症患者的病历。我们确定了五例肾血管炎病例：三例患者被诊断为血清阴性抗中性粒细胞胞浆抗体 (ANCA) 相关性血管炎，一例患者为血清阳性 ANCA 相关性血管炎，一例患者被诊断为 IgA 血管炎。这些病例中，有四例患者接受了nivolumab 治疗，一例患者接受了 tremelimumab 治疗。所有患者均有镜下血尿，五例中有四例 ANCA 血清学阴性，一例患者同时伴有肺部受累和阳性 ANCA 血清学，所有患者均在诊断时出现严重急性肾损伤，血肌酐>4.50mg/dL。所有患者均通过停用 CPI 并开始使用皮质类固醇和利妥昔单抗进行治疗。三名患者接受了血浆置换；其中两名患者需要肾脏替代治疗，包括肺部受累的患者。利妥昔单抗治疗后，所有患者的肾功能均有部分或完全恢复。两名患者在诊断后 8 个月内死于恶性肿瘤进展。无患者出现血管炎复发。我们表明，CPI 可引起不同类型的肾血管炎，这些血管炎主要为 ANCA 阴性，并表现为严重急性肾损伤。尽管缺乏强有力的证据，但使用皮质类固醇和利妥昔单抗治疗类似于原发性血清阳性 ANCA 相关性血管炎的治疗方法，具有良好的耐受性和良好的肾脏预后。
