一项中国慢性乙型肝炎门诊核苷(酸)类药物经治患者肾脏功能损害的横断面研究

A cross-sectional study of renal dysfunction in chronic hepatitis B outpatients treated with nucleos(t)ide drugs in China

目的通过比较门诊慢性乙型肝炎(CHB)患者肾功能指标异常比例,探讨核苷(酸)类药物(NAs)抗病毒治疗史与肾功能指标异常的相关性。方法采用横断面设计,进行肾功能筛查,收集基线特征、抗病毒治疗史、肾功能指标,包括估算的肾小球滤过率(eGFR)、血尿素氮、血肌酐、血尿酸、尿β2-微球蛋白、α1-微球蛋白和尿蛋白。按肾功能指标异常定义和标准,进行慢性肾脏病(CKD)-1/2及相关风险因素分析,肾小管指标与风险因素相关性分析,以及抗病毒治疗时长与肾小管风险的相关性。对数据进行单因素和多因素回归分析。结果共纳入全国47家医院门诊2703例患者,男性70.7%;平均年龄47.5岁;15.5%的患者合并高血压,14.6%的患者合并慢性肾病,11.3%的患者合并糖尿病。CKD 1/2期共占15.4%。视黄醇结合蛋白、尿β2-微球蛋白或尿α1-微球蛋白提示肾小管损伤率分别为10.4%,27.1%和18.4%。肾小管损伤风险可能与抗病毒治疗时长有关(OR=1.06,95%CI=1.028~1.093)。多因素分析结果显示:eGFR<90 ml/min相关风险因素为年龄40~60岁或>60岁、高病毒载量、高血压控制不佳、使用肾毒性药物、肝纤维化状态、乙型肝炎家族史;eGFR<60 ml/min相关风险因素为女性、失代偿期肝硬化、糖尿病控制不佳、乙型肝炎家族史。结论门诊CHB经治患者存在较高比例慢性肾损害,包括肾小管早期损害。提示使用NAs前需评估基线肾功能,治疗过程中应密切监测,定期监测肾小管损伤指标较估算的eGFR能更早地发现肾损伤风险。

Objective To compare the proportion of abnormal renal function indexes in outpatients with chronic hepatitis B(CHB),and to further explore the correlation between the history of nucleos(t)ide analogues(NA)antiviral therapy and abnormal renal function indexes.Methods A cross-sectional design was adopted for renal function screening.Baseline characteristics,history of antiviral treatment,and renal function indexes were collected,including glomerular filtration rate(eGFR),blood urea nitrogen,blood creatinine,blood uric acid,and urine β2-microglobulinα1-microglobulin and urinary protein.According to the definition and standard of abnormal renal function indexes,the correlation between chronic kidney disease(CKD)-1/2 and related risk factors,renal tubular indicators and risk factors,and the correlation between antiviral treatment duration and renal tubular risk were analyzed.The data were analyzed by single and multi-factor regression.Results 2703 outpatients from 47 hospitals across the country were enrolled.70.7%were males with an average age of 47.5 years.15.5%of cases had hypertension,14.6%cases had chronic kidney disease,11.3%cases had diabetes,and 15.4%had CKD 1/2.Retinol-binding protein,urinaryβ2-microglobulin or urinaryα1-microglobulin showed renal tubular damage rates of 10.4%,27.1%and 18.4%,respectively.Renal tubular damage risk was related to the antiviral treatment duration(OR=1.06,95%CI=1.028~1.093).Multivariate analysis results showed that the risk factors related to eGFR<90 ml/min in male were 40-60 or>60 years old,high viral load,poorly controlled hypertension,use of nephrotoxic drugs,liver fibrosis status,family history of hepatitis B;while the risk factors related to eGFR<60 ml/min in female were decompensated cirrhosis,poorly controlled diabetes,and family history of hepatitis B.Conclusion CHB outpatients have a high proportion of chronic kidney damage,including early renal tubular damage,which suggests that baseline renal function should be assessed before NA use and closely monitored during the treatment.Regular monitoring of the renal tubular damage index can detect the risk of kidney damage earlier than the estimated eGFR.