Supplementary Material for: Renal immune-related adverse event difficult to diagnose during nivolumab treatment for nasopharyngeal carcinoma: Case report.

Introduction: Immune-related adverse events (irAEs) from nivolumab can affect any organ, but renal impairment is less common than effects on other organs. We encountered a case in which a renal irAE was difficult to diagnose due to mild renal dysfunction. Case Presentation: We report the case of a 65-year-old man with hypopharyngeal carcinoma treated with radiotherapy and cisplatin. Histopathological examination after reconstructive surgery showed extranodal invasion. Two months after completing treatment, computed tomography showed multiple lung metastases. We determined that the tumors were platinum-resistant and initiated treatment with nivolumab. Pyuria, worsening renal function, and elevation of C-reactive protein (CRP) to 16 mg/dL were observed 203 days after the first dose and nivolumab was discontinued. We considered the possibility of renal irAE, but did not perform renal biopsy because creatinine was not highly elevated. We administered antibiotics for urinary tract infection, but CRP rose to 20 mg/dL and his general condition gradually worsened. Arthralgia in both knees and elbows appeared around the same time and gallium scintigraphy showed polyarticular accumulations. After diagnosing irAE arthritis, 20 mg of prednisolone was administered. Arthralgia and inflammatory responses improved, along with urinary findings and tubular markers. Retrospectively, pyuria, mild renal dysfunction, and elevated CRP were considered to reflect renal irAE. Conclusion: In some cases of mild renal dysfunction, as in the present case, biopsy may not be performed and the diagnosis may be missed. Renal irAEs should be kept in mind when abnormal urinalysis results and renal dysfunction are observed.

引言：纳武利尤单抗（nivolumab）引发的免疫相关不良事件（immune-related adverse events, irAEs）可累及任何器官，但肾损害的发生率低于其他器官受累情况。我们曾遇到1例因轻度肾功能不全导致肾脏免疫相关不良事件难以确诊的病例。
病例报告：本文报告1例接受放疗联合顺铂治疗的65岁下咽癌男性患者，重建术后病理检查显示存在结外侵犯。治疗结束2个月后，计算机断层扫描提示多发肺转移，我们判断肿瘤为铂类耐药型，遂启动纳武利尤单抗治疗。首次给药后203天，患者出现脓尿、肾功能恶化，C反应蛋白（C-reactive protein, CRP）升至16mg/dL，遂停用纳武利尤单抗。我们考虑存在肾脏免疫相关不良事件的可能，但因肌酐升高幅度不显著，未行肾活检。予抗生素治疗尿路感染，但CRP升至20mg/dL，患者一般状况逐渐恶化。同期患者出现双膝及肘关节关节痛，镓闪烁显像（gallium scintigraphy）显示多关节浓聚征象。确诊为免疫相关不良事件相关性关节炎后，予20mg泼尼松龙治疗，关节痛、炎症反应、尿液检查结果及肾小管标志物均得到改善。回顾性分析认为，脓尿、轻度肾功能不全及CRP升高均符合肾脏免疫相关不良事件的表现。
结论：部分轻度肾功能不全病例（如本例）可能未行肾活检而导致漏诊。当出现尿液分析异常及肾功能不全时，应警惕肾脏免疫相关不良事件的发生可能。