HIV感染/艾滋病患者富马酸替诺福韦二吡呋酯相关范可尼综合征临床特征分析

Analysis on clinical characteristics of tenofovir disoproxil fumarate-related Fanconi syndrome in patients with HIV infection/AIDS

目的探讨HIV感染/艾滋病(HIV/AIDS)患者富马酸替诺福韦二吡呋酯(TDF)相关范可尼综合征(FS)的临床特征。方法检索医院信息系统,收集2017年12月至2021年2月在云南省传染病医院住院且采用含TDF的抗反转录病毒治疗(ART)并诊断为FS的HIV/AIDS患者的病历资料,包括性别、年龄、体重、体重指数(BMI)、ART治疗方案和时间、诊断FS时间、主要临床表现、入院及出院实验室检查结果,双能X射线骨密度检查结果以及干预和转归等信息,进行回顾性分析。结果设定时段内诊断为TDF相关FS的HIV/AIDS患者共16例,其中完全型FS 6例,不完全型FS 10例;7例合并慢性丙型肝炎、高血压病、肝癌和抑郁症等慢性疾病;16例患者接受含TDF的ART治疗时间最短20个月,最长168个月,平均68个月;FS的初始症状多为骨痛、乏力、恶心、纳差、多饮、多尿,体重下降等,从出现初始症状至确诊FS的时间最短2周,最长24周,平均7周。实验室检查结果显示,16例患者在血糖正常情况下尿葡萄糖均为阳性,14例尿蛋白阳性,低尿磷、低尿钙、低尿钾和低尿钠者分别为11、11、4和4例;低血磷、低血钾、低血钙和低血钠者分别为13、12、8和7例;11例血清肌酐升高,10例血尿酸降低,1例血尿酸增高。15例患者行双能X射线骨密度检查,其中骨密度正常、减低和骨质疏松者分别为2、2和11例。诊断为TDF相关FS后,16例患者均立即停用TDF,更换不含TDF的ART方案并对症治疗平均29 d后,上述症状程度减轻,部分实验室检查指标恢复至参考值范围,预后较好。结论TDF相关FS多在用药68个月发生,FS临床症状无特异性,实验室检查结果均为在血糖正常情况下尿葡萄糖阳性,多数出现低血磷,低尿磷,低尿钙,骨质疏松。停用TDF、更换为不含TDF的ART方案并对症治疗后预后较好。

Objective To explore the clinical characteristics of tenofovir disoproxil fumarate(TDF)-related Fanconi syndrome(FS)in patients with HIV infection/AIDS(HIV/AIDS).Methods The medical records of patients with HIV/AIDS who were hospitalized in Yunnan Provincial Hospital of Infectious Diseases from December 2017 to February 2021,treated with antiretroviral therapy(ART)containing TDF,and diagnosed as FS were collected by searching hospital information system.Information such as gender,age,body weight,body mass index(BMI),ART treatment regimen and period,time of FS diagnosis,main clinical characteristics,results of laboratory test at admission and discharge,dual energy X-ray bone mineral density(BMD)test results,and interventions and outcomes were retrospectively analyzed.Results A total of 16 HIV/AIDS patients were diagnosed with TDF-related FS in the setting period,including 6 patients with complete FS and 10 with incomplete FS.FS were accompanied with chronic hepatitis C,hypertension,liver cancer,or depression in 7 patients.Sixteen patients received ART containing TDF for a minimum of 20 months and a maximum of 168 months with an average time of 68 months.The initial symptoms of FS were bone pain,fatigue,nausea,anorexia,polydipsia,polyuria,weight loss,etc.The time from initial symptoms to diagnosis of FS was 2 weeks at least,24 weeks at most,with an average time of 7 weeks.Laboratory test results were as follows:all 16 patients had positive urine glucose under normoglycemic conditions and 14 patients had positive urine protein;11,11,4,and 4 patients had low urine phosphorus,hypocalciuria,hypokalemia,and hyponatruria,respectively;13,12,8,and 7 patients had hypophosphatemia,hypokalemia,hypocalcemia,and hyponatremia,respectively;11 patients had serum creatinine increase;10 patients had serum uric acid decrease;1 patient had serum uric acid increase.Dual energy X-ray BMD detection was performed in 15 patients,of which 2,2,and 11 patients had normal,reduced,and osteoporotic BMD,respectively.After diagnosis of TDF-related FS,16 patients stopped using TDF immediately.After replacement of ART protocol without TDF and symptomatic treatment for an average time of 29 days,the above symptoms were alleviated,and some laboratory test indicators returned to the reference value range.The prognosis was good.Conclusions TDF-related FS mostly occurs within 68 months of drug use.The clinical symptoms of FS are nonspecific.Laboratory tests show that urine glucose is positive under normal blood glucose.Most of the patients have low blood phosphorus,low urine phosphorus,hypocalciuria,and osteoporosis.The prognosis is better after discontinuing TDF,replacing therapy with ART regimen without TDF,and giving symptomatic treatments.