Hanna Ramy M, Selamet Umut, Bui Patrick, Sun Shih-Fan, Shenouda Olivia, Nobakht Niloofar, Barsoum Marina, Arman Farid, Rastogi Anjay
Division of Nephrology, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, California, USA.
Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, California, USA.
Case Rep Nephrol Dial. 2018 Aug 10;8(2):171-177. doi: 10.1159/000491631. eCollection 2018 May-Aug.
Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein 1 (PD-1) antigen and induces an immune response against tumor tissues. It has been successful in inducing remission in patients with severe metastatic disease, often refractory to other chemotherapeutic agents. The risk of injury of other organ systems has been noted with reported cases of glomerular disease and endocrine disease. In addition, hypophysitis as well as dermatological and gastroenterological side effects have been reported. Renal injury with immune checkpoint inhibitors like nivolumab and pembrolizumab is usually mediated via interstitial nephritis, though glomerular disease presentations like anti-neutrophil cytoplasmic antibody-associated vasculitis, immune complex disease, and thrombotic microangiopathy have also been reported. We report a 70-year-old Caucasian male who underwent treatment with pembrolizumab for adenocarcinoma of the lung. He developed acute adrenal insufficiency and concomitant severe hypotension upon presentation. He did not require renal replacement therapy, rather his severe acute kidney injury resolved with hydration, normalization of blood pressures with vasopressors, and treatment with high-dose corticosteroids. His urinary indices (fractional excretion of urea, FEUrea) and clinical course were highly suspicious for acute tubular necrosis that resolved quickly after treating his underlying adrenalitis. The urinary sediment, proteinuria, and clinical course were not typical for the usually expected renal lesion of interstitial nephritis in patients treated with immune checkpoint inhibitors.
帕博利珠单抗是一种免疫检查点抑制剂,它靶向程序性细胞死亡蛋白1(PD-1)抗原,并诱导针对肿瘤组织的免疫反应。它已成功诱导重症转移性疾病患者缓解,这些患者通常对其他化疗药物耐药。已有报道指出,使用该药物存在导致其他器官系统损伤的风险,如肾小球疾病和内分泌疾病。此外,还报告了垂体炎以及皮肤和胃肠道副作用。像纳武利尤单抗和帕博利珠单抗这样的免疫检查点抑制剂引起的肾损伤通常是通过间质性肾炎介导的,不过也有报道出现过抗中性粒细胞胞浆抗体相关性血管炎、免疫复合物病和血栓性微血管病等肾小球疾病表现。我们报告了一名70岁的白种男性,他接受了帕博利珠单抗治疗肺癌。他就诊时出现了急性肾上腺功能不全并伴有严重低血压。他不需要肾脏替代治疗,而是通过补液、使用血管升压药使血压恢复正常以及大剂量皮质类固醇治疗,其严重的急性肾损伤得以缓解。他的尿液指标(尿素排泄分数,FEUrea)和临床病程高度怀疑为急性肾小管坏死,在治疗其潜在的肾上腺炎后迅速好转。尿液沉渣、蛋白尿和临床病程并不符合免疫检查点抑制剂治疗患者中通常预期的间质性肾炎肾脏病变特征。