长期口服抗病毒药物的慢性乙型肝炎患者肾功能指标异常的影响因素分析

宁会彬; 靳慧鸣; 李宽; 彭真; 李威; 尚佳

doi:10.3969/j.issn.1001-5256.2021.08.011

长期口服抗病毒药物的慢性乙型肝炎患者肾功能指标异常的影响因素分析

DOI: 10.3969/j.issn.1001-5256.2021.08.011

河南省人民医院感染科，郑州 450000

基金项目:

“十三五”国家科技重大专项 (2018ZX10302205-004)

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：宁会彬负责收集资料，设计撰写文章；靳慧鸣负责数据统计分析；李宽、彭真负责收集和分析资料；李威负责指导写作；尚佳负责指导写作，修改文章。

详细信息

通信作者:
尚佳，shangjia666@126.com

中图分类号: R512.62
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出版历程
- 收稿日期: 2020-12-24
- 录用日期: 2021-01-26
- 出版日期: 2021-08-20

Influencing factors for abnormal renal function markers in chronic hepatitis B patients receiving long-term oral administration of entecavir/tenofovir disoproxil fumarate

Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou 450000, China

Research funding:

National Key R&D Program of China (2018ZX10302205-004)

摘要

摘要: 目的探讨长期口服抗病毒药物的慢性乙型肝炎患者肾功能指标异常情况及影响因素。方法回顾性收集2019年1月— 2019年12月河南省人民医院就诊长期口服恩替卡韦(ETV)或富马酸替诺福韦(TDF)的681例慢性乙型肝炎患者的临床资料。所有患者均进行血液肾功能[尿素、肌酐、视黄醇结合蛋白(RBP)、血胱抑素C(Cys C)、β2微球蛋白(β2-MG)]、尿液肾功能[尿α1-微球蛋白(α1-MG)、尿Cys C、尿N-已酰-β-D-氨基葡萄糖苷酶(NAG)]及尿常规检测。分析患者肾功能指标异常发生率。计数资料组间比较采用McNemar’s检验。利用多因素logistic回归筛选慢性乙型肝炎患者尿液中肾指标异常发生的独立影响因素。结果 681例患者平均年龄(39.8±11.0)岁，平均用药1.88(0.80~3.16)年；男性417例，女性264例；肝硬化发生率27.02%(184/681)，ETV与TDF用药患者分别为442例、239例。血肾功能检测项目异常率分别为尿素6.9%(47/681)、肌酐0.15%(1/681)、RBP 0(0/681)、血Cys C 2.21%(15/681)、β2-MG 5.03%(30/681)，尿蛋白异常情况为7.29%(49/672)，尿肾功能检测项目异常率分别为α1-MG 38.62%(263/681)、NAG 37.74%(257/681)、尿Cys C 19.38%(132/681)。尿检异常率高于血检(P＜0.001)。以尿α1-MG作为因变量进行多因素logistic回归分析结果显示，性别(OR=0.293, 95%CI：0.204~0.419)、年龄(OR=1.298, 95%CI：1.108~1.521)、核苷药物种类(OR=2.100, 95%CI：1.431~3.083)为其影响因素(P值均＜0.05)。以尿NAG作为因变量进行多因素logistic回归分析结果显示, 年龄(OR=1.177, 95%CI：1.008~1.375，P=0.040)为其影响因素。结论尿肾功能检测指标(尤其是尿α1-MG和尿NAG)比血液检测指标更能早期发现慢性乙型肝炎患者肾损伤，老年男性患者及接受TDF治疗者更容易出现肾功能异常，未观察到用药时长及肝硬化增加慢性乙型肝炎患者肾损伤的发生风险。
- 乙型肝炎, 慢性 /
- 肾疾病 /
- 影响因素分析
Abstract: Objective To investigate the status of abnormal renal function markers and related influencing factors in chronic hepatitis B (CHB) patients receiving oral antiviral drugs for a long time. Methods A retrospective analysis was performed for the clinical data of 681 CHB patients who attended Henan Provincial People's Hospital from January to December 2019 and received long-term oral administration of entecavir (ETV)/tenofovir disoproxil fumarate (TDF). All patients received the measurement of blood renal function markers (urea, creatinine, retinol-binding protein [RBP], cystatin C [Cys-C], and β2-microglobulin [β2-MG]), urinary renal function markers (α1-microglobulin [α1-MG], Cys-C, and N-acetyl-β-D-glucosaminidase [NAG]), and urine routine parameters. The incidence rate of abnormal renal function markers were analyzed. The McNemar's test was used for comparison of categorical data between groups, and the multivariate logistic regression analysis was used to investigate independent influencing factors for abnormal renal markers in urine. Results The 681 patients had a mean age of 39.8±11.0 years and received medication for 1.88 (0.80-3.16) years. There were 417 male patients and 264 female patients, and the incidence rate of liver cirrhosis was 27.02% (184/681). Of all 681 patients, 442 received ETV and 239 received TDF. The measurement of blood renal function markers showed that urea, creatinine, retinol-binding protein, Cys-C, and β2-MG had an abnormal rate of 6.9% (47/681), 0.15% (1/681), 0(0/681), 2.21% (15/681), and 5.03% (30/681), respectively, and the abnormal rate of urinary protein was 7.29% (49/672). The measurement of urinary renal function markers showed that α1-MG, NAG, and Cys-C had an abnormal rate of 38.62% (263/681), 37.74% (257/681), and 19.38% (132/681), respectively. The abnormal rate of urine test was higher than that of blood test (P < 0.001). The multivariate logistic regression analysis with urinary α1-MG as the dependent variable showed that sex (odds ratio [OR]=0.293, 95% confidence interval [CI]: 0.204-0.419, P < 0.05), age (OR=1.298, 95%CI: 1.108-1.521, P < 0.05), and type of nucleoside drug (OR=2.100, 95%CI: 1.431-3.083, P < 0.05) were influencing factors. The multivariate logistic regression analysis with urinary NAG as the dependent variable showed that age (OR=1.177, 95%CI: 1.008-1.375, P=0.040) was an influencing factor. Conclusion Compared with blood renal function markers, urinary renal function markers can identify renal injury earlier in CHB patients, and the elderly patients and the patients receiving TDF are more likely to develop abnormal renal function. However, it is not observed whether the duration of medication and liver cirrhosis can increase the risk of renal injury in CHB patients.
- Hepatitis B, Chronic /
- Kidney Diseases /
- Root Cause Analysis

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表 1 血BUN检测与尿Cys C检测异常情况比较

指标		尿Cys C检测		合计
指标		异常	正常	合计
血BUN检测	异常	6	41	47
	正常	126	508	634
合计		132	549	681
注：配对McNemar’s检验，P＜0.001。

下载: 导出CSV

表 2 681例CHB患者尿α1-MG异常的多因素logistic回归分析

变量	β值	SE	Wald χ²	P值	OR(95%CI)
性别	-1.228	0.184	44.816	＜0.001	0.293(0.204~0.419)
年龄	0.261	0.081	10.381	0.001	1.298(1.108~1.521)
核苷药物种类	0.742	0.196	14.353	＜0.001	2.100(1.431~3.083)
常数项	-0.995	0.256	13.908	＜0.001	0.385

下载: 导出CSV

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