Department of Respiratory Medicine, Osaka General Medical Center, Osaka, Japan.
Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka, Japan.
Nephron. 2022;146(1):58-63. doi: 10.1159/000518774. Epub 2021 Sep 17.
Tyrosine kinase inhibitors (TKIs) that target the epidermal growth factor receptor (EGFR) have shown highly favourable outcomes in patients with advanced-stage non-small-cell lung cancer (NSCLC). The adverse effects of EGFR-TKIs are generally less severe than those of conventional cytotoxic therapies. We report a patient with NSCLC who presented with acute kidney injury associated with biopsy-proven acute tubular injury during osimertinib treatment and whose renal function recovered after reducing the osimertinib dose. A 61-year-old male smoker complained of dyspnoea on exertion for 1 month before his visit to the medical centre. He was diagnosed with lung adenocarcinoma of the left lower lobe (cT4N3M1a, stage IVA) and was positive for an EGFR mutation (exon 19 deletion). Osimertinib was initiated at 80 mg/day. At treatment initiation, the patient's serum creatinine level was 0.64 mg/dL, with microscopic haematuria; by day 83, this level had increased to 1.33 mg/dL, with proteinuria. On day 83, we reduced the osimertinib dose to 40 mg/day and performed a kidney biopsy on day 98. The histological diagnosis was tubular injury with IgA deposition. Based on the clinical course and histological findings, we speculated that the kidney injury was associated with osimertinib. After dose reduction, the patient's serum creatinine level decreased to 1.07 mg/dL, and proteinuria disappeared. He maintained a partial response for >6 months after osimertinib administration. We report the first case of biopsy-proven mild IgA deposition, crescent formation, and tubular injury probably caused by osimertinib and demonstrate how reducing the osimertinib dose could strike a balance between its anti-cancer efficacy and adverse effects.
针对表皮生长因子受体 (EGFR) 的酪氨酸激酶抑制剂 (TKI) 在晚期非小细胞肺癌 (NSCLC) 患者中显示出极好的效果。EGFR-TKI 的不良反应通常比传统细胞毒性疗法的不良反应轻。我们报告了一例 NSCLC 患者，该患者在接受奥希替尼治疗期间出现活检证实的急性肾小管损伤相关的急性肾损伤，并且在减少奥希替尼剂量后肾功能恢复。一位 61 岁男性吸烟者在前往医疗中心就诊前 1 个月出现劳力性呼吸困难。他被诊断为左肺下叶肺癌（cT4N3M1a，IV 期），并存在 EGFR 突变（外显子 19 缺失）。奥希替尼以 80mg/天开始治疗。治疗开始时，患者的血清肌酐水平为 0.64mg/dL，伴有镜下血尿；第 83 天，该水平升高至 1.33mg/dL，伴有蛋白尿。第 83 天，我们将奥希替尼剂量减少至 40mg/天，并在第 98 天进行了肾活检。组织学诊断为伴有 IgA 沉积的肾小管损伤。根据临床过程和组织学发现，我们推测肾脏损伤与奥希替尼有关。减少剂量后，患者的血清肌酐水平降至 1.07mg/dL，蛋白尿消失。他在奥希替尼给药后维持了超过 6 个月的部分缓解。我们报告了首例活检证实的轻度 IgA 沉积、新月体形成和可能由奥希替尼引起的肾小管损伤的病例，并展示了如何通过减少奥希替尼剂量在其抗癌疗效和不良反应之间取得平衡。
