Department of Pharmacy, Henry Ford Hospital, Detroit, Michigan, USA.
Pharmacotherapy. 2012 Jan;32(1):e12-6. doi: 10.1002/PHAR.1013.
Fanconi's syndrome is a serious condition characterized by type II proximal renal tubular dysfunction, with urinary loss of glucose, amino acids, phosphate, bicarbonate, and potassium. Ifosfamide-induced Fanconi's syndrome is reported in about 1.4-5% of children being treated for solid tumors, yet only a few cases have been reported in adults. We describe a 54-year-old man who came to the hospital with symptoms of neutropenic fever 4 days after his fourth cycle of ifosfamide and doxorubicin treatment for recurrent sarcoma with metastases to the lung. During admission, he was noted to have severe renal tubular dysfunction; ifosfamide-induced nephrogenic diabetes insipidus and Fanconi's syndrome were suspected. He received supportive therapy that resulted in incomplete resolution of signs and symptoms. The patient was discharged after a 5-day hospital stay when his white blood cell count increased from 0.1-2.5 × 10(3) /mm(3) and his fever had resolved. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of diabetes insipidus and Fanconi's syndrome and his use of ifosfamide. This dual diagnosis of diabetes insipidus and Fanconi's syndrome in an adult makes this case unusual, as well as therapeutically challenging. We conducted a review of the existing literature regarding ifosfamide-induced Fanconi's syndrome and describe the proposed mechanisms and therapeutic options. This case suggests that patients treated with ifosfamide should be monitored closely for renal function to identify, and perhaps prevent, these rare adverse events. Preliminary animal models show promise for adding N-acetylcysteine to ifosfamide treatment, but more research is necessary before using this drug as a therapeutic option.
范可尼综合征是一种严重的疾病，其特征为 II 型近端肾小管功能障碍，表现为尿糖、氨基酸、磷酸盐、重碳酸盐和钾丢失。异环磷酰胺治疗实体瘤时约有 1.4%-5%的儿童会发生范可尼综合征，但在成人中仅有少数病例报道。我们描述了一位 54 岁男性，他在接受第四周期异环磷酰胺和多柔比星治疗复发性肉瘤（肺转移）后第 4 天因中性粒细胞减少性发热来院就诊。住院期间，他被发现存在严重的肾小管功能障碍；考虑为异环磷酰胺引起的肾性尿崩症和范可尼综合征。他接受了支持治疗，但症状和体征未完全缓解。在白细胞计数从 0.1-2.5×10(3) /mm(3)增加、发热消退后，他在住院 5 天后出院。使用 Naranjo 药物不良反应发生概率量表评估显示，患者发生尿崩症和范可尼综合征与使用异环磷酰胺之间可能存在因果关系（评分 7）。该成人患者同时发生尿崩症和范可尼综合征较为罕见，治疗也极具挑战性。我们对异环磷酰胺引起的范可尼综合征的现有文献进行了回顾，并描述了其发病机制和治疗选择。该病例提示，接受异环磷酰胺治疗的患者应密切监测肾功能，以识别和预防这些罕见的不良反应。初步动物模型显示，在异环磷酰胺治疗中添加 N-乙酰半胱氨酸有希望，但在将该药物作为治疗选择之前，还需要进行更多的研究。
