肾移植后他克莫司相关可逆性后部脑病综合征文献病例分析

Literature case analysis of tacrolimus-associated posterior reversible encephalopathy syndrome in patients after kidney transplantation

目的探讨发生在肾移植受者的他克莫司相关可逆性后部脑病综合征(PRES)的临床特征。方法检索国内外相关数据库(截至2020年8月),收集肾移植后他克莫司相关PRES的病例报告类文献,记录患者的一般情况、他克莫司应用情况(用药途径、剂量、血药浓度、联合用药方案等)以及PRES发生时间、临床表现、影像学特征、干预措施及转归等信息,进行描述性统计分析。结果纳入分析的患者共16例,男性7例,女性9例;年龄7~54岁,中位年龄26岁,<18岁者6例,≥18岁10例;静脉和口服用药各8例;13例有联合用药方案记录,联用1、2、3种免疫抑制剂者分别为3、8和2例;PRES的发生时间为肾移植术后3 d~3个月,10例(62.5%)发生在术后1个月内。发生PRES时,13例行他克莫司血药浓度检测的患者中11例血药浓度未超过治疗窗范围上限。PRES的主要症状包括抽搐/癫痫样发作(11例)、视觉异常(7例)、持续性头痛(6例)以及昏迷或意识障碍(6例)。16例患者均行头部CT和/或磁共振成像检查,15例可见脑水肿或血管源性脑水肿的影像学特征,病变部位主要在枕叶(13例)、顶叶(12例)和额叶(8例)。停用或减少他克莫司剂量和/或给予对症及支持治疗2~44 d(中位时间为9 d),16例患者症状均消失,15例患者影像学复查脑水肿或血管源性脑水肿等病变消退。结论肾移植受者他克莫司相关PRES多发生在肾移植术后3个月内,临床表现与其他原因所致PRES相似。停用他克莫司、减少药物剂量和/或给予对症治疗,症状多很快消失,影像学改变恢复正常。

Objective To explore the clinical features of tacrolimus-associated posterior reversible encephalopathy syndrome(PRES)in patients after kidney transplantation.Methods Relevant databases at home and abroad were searched as of August 2020,and case reports of tacrolimus-associated PRES after kidney transplantation were collected.Clinical information including patient′s basic characteristics,tacrolimus application(such as route of administration,dose,blood concentration,drug combination regimen,etc.),and the occurrence time,clinical manifestation,imaging characteristics,intervention measures,and outcomes of PRES were extracted and analyzed by descriptive statistical method.Results A total of 16 patients were enrolled in the study,including 7 males and 9 females,aged from 7 to 54 years with a median age of 26 years.Of them,6 patients were<18 years old and 10 patients were≥18 years old.Among the 16 patients,8 received intravenous administration and 8 oral administration.Thirteen patients had records of drug combination regimen and 1,2,and 3 immunosuppressants were combined in 3,8,and 2 patients,respectively.PRES occurred from 3 days to 3 months after renal transplantation and 10 patients(62.5%)occurred within 1 month after operation.Eleven of 13 patients who underwent tacrolimus plasma concentrations testing did not exceed the upper limit of the treatment window when PRES occurred.The main symptoms of PRES included convulsions/seizures-like seizures(in 11 patients),visual abnormalities(in 7 patients),persistent headache(in 6 patients),and coma or disturbance of consciousness(in 6 patients).CT and/or magnetic resonance imaging were performed in all 16 patients.Imaging features of cerebral edema or vasogenic cerebral edema were found in 15 patients and the lesions located mainly in occipital lobe(13 patients),parietal lobe(12 patients),and the frontal lobe(8 patients).After discontinuation or reduction of the tacrolimus dose and/or giving symptomatic and supportive treatments for 2-44 days(the median time of 9 days),symptoms subsided in all 16 patients and imaging examination showed cerebral edema,vasogenic cerebral edema,and other lesions subsided in 15 patients.Conclusions Tacrolimus-associated PRES mostly occurred within 3 months after renal transplantation,which was not related to the route of administration or blood concentration of tacrolimus.The clinical manifestations of tacrolimus-associated PRES were similar to those caused by other factors.After discontinuation of tacrolimus,reduction of drug dose and/or administration of symptomatic treatment,most of the symptoms disappeared quickly and the imaging changes returned to normal.