Saida K, Kamei K, Ogura M, Matsumura S, Kano Y, Sato M, Andoh A, Ishikura K
Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan.
Department of Medicine, Shiga University of Medical Science, Shiga, Japan.
Transplant Proc. 2018 Dec;50(10):3925-3927. doi: 10.1016/j.transproceed.2018.04.039. Epub 2018 Apr 18.
Azathioprine (AZA) is the drug recommended for the continuation of immunosuppressive treatment after renal transplant in women during pregnancy.
A 37-year-old Japanese female developed agranulocytosis and severe alopecia after initiation of AZA (50 mg), used as an alternative to mycophenolate mofetil (MMF, 1000 mg) therapy in anticipation of a planned pregnancy. Within 4 days of the initiation of AZA therapy, the patient developed a high fever, leucopenia, and cranial alopecia. Genetic testing revealed a homozygous polymorphism of NUDT15 (rs116855232, NM_018283.3:c.415C>T: p.Arg139Cys), which has previously been identified as a risk factor for AZA-related complications in patients with inflammatory bowel disease.
Genetic screening for NUDT15 could contribute to the prevention of serious adverse reactions to AZA and provide the opportunity for personalized medicine. Identification of a safe alternative to MMF during pregnancy after a renal transplant is a problem to be resolved in the future.
硫唑嘌呤（AZA）是推荐用于肾移植术后女性孕期继续免疫抑制治疗的药物。
一名37岁日本女性在开始使用AZA（50毫克）后出现粒细胞缺乏症和严重脱发，AZA是在计划怀孕时作为霉酚酸酯（MMF，1000毫克）治疗的替代药物使用的。在AZA治疗开始后的4天内，患者出现高热、白细胞减少和头部脱发。基因检测显示NUDT15存在纯合多态性（rs116855232，NM_018283.3:c.415C>T:p.Arg139Cys），此前已被确定为炎症性肠病患者发生AZA相关并发症的危险因素。
对NUDT15进行基因筛查有助于预防AZA的严重不良反应，并为个性化医疗提供机会。确定肾移植术后孕期MMF的安全替代药物是未来有待解决的问题。
