尿Netrin-1及KIM-1水平对慢性乙型肝炎患者核苷(酸)类药物相关肾损伤的预测价值

摘要/Abstract

摘要： 目的探讨尿神经导向因子(Netrin-1)及肾损伤因子(KIM-1)水平对慢性乙型肝炎(CHB)患者核苷(酸)类药物相关肾损伤的预测价值。方法选取2020年11月—2022年5月哈励逊国际和平医院收治的180例CHB患者,按是否使用核苷(酸)类抗病毒药物分为观察组(120例)与对照组(60例)。观察组按用药分为替诺福韦组(48例)、恩替卡韦组(72例);按是否发生肾损伤分为损伤组(54例)与无损伤组(66例)。比较各组年龄、性别、病程、CHB家族史、基线估算肾小球滤过率(eGFR)及尿Netrin-1、KIM-1水平;采用多因素logistic回归分析评估肾损伤的独立危险因素;绘制ROC曲线评估尿Netrin-1、KIM-1的预测效能。结果对照组与观察组(替诺福韦组、恩替卡韦组)一般临床特征比较差异无统计学意义(P>0.05);损伤组与无损伤组尿Netrin-1[(500.30±129.68)μg/L vs. (262.59±98.42)μg/L]、KIM-1[(100.04±14.43)μg/L vs. (76.24±13.40)μg/L](P<0.05)。多因素logistic回归显示,尿Netrin-1(OR=1.013,95%CI:1.008～1.018)、KIM-1(OR=1.100,95%CI:1.054～1.147)升高是CHB患者核苷(酸)类药物相关肾损伤的独立危险因素(P<0.05)。ROC曲线分析表明,Netrin-1、KIM-1单独预测的AUC分别为0.908、0.857,联合检测AUC升至0.946,预测效能优于单一指标。结论尿Netrin-1和KIM-1水平可作为早期预测CHB患者核苷(酸)类药物相关肾损伤的敏感指标,联合检测有助于提高预测准确性,为临床早期干预提供参考。

关键词: 慢性乙型肝炎, 核苷(酸)类药物, 肾损伤, Netrin-1, KIM-1, 预测价值

Abstract: Objective This study identifies the predictive performance of urinary Netrin-1 and kidney injury molecule 1 (KIM-1) for renal injury related to nucleoside/nucleotide analog therapy in patients with chronic hepatitis B. Methods A total of 180 patients with chronic hepatitis B were enrolled in Harrison International Peace Hospital between November 2020 and May 2022. Patients were divided into an observation group (120 cases) receiving nucleoside/nucleotide analogs and a control group (60 cases) without antiviral therapy. The observation group was further divided into a tenofovir group (n=48) and an entecavir group (n=72) according to medication use, and into a renal injury group (n=54) and a non-injury group (n=66) according to the occurrence of renal injury. Baseline characteristics, estimated glomerular filtration rate (eGFR), urinary Netrin-1, and kidney injury molecule-1 (KIM-1) values were compared across groups. Multivariate logistic regression analysis was performed to identify independent risk factors. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive value of Netrin-1 and KIM-1. Results Baseline clinical characteristics did not differ significantly among the control group, tenofovir group, and entecavir group (P>0.05). Urinary Netrin-1 (500.30 ± 129.68 μg/L) and KIM-1 (100.04 ± 14.43 μg/L) in the renal injury group were significantly higher than those in the non-injury group (262.59 ± 98.42 μg/L and 76.24 ± 13.40 μg/L, respectively) (P<0.05). Multivariate logistic regression demonstrated that elevated urinary Netrin-1 (OR=1.013, 95%CI: 1.008~1.018) and KIM-1 (OR=1.100, 95%CI: 1.054~1.147) were independent risk factors for nucleos(t)ide analog-associated renal injury in patients with CHB (P<0.05). The area under the ROC curve (AUC) was 0.908 for Netrin 1 and 0.857 for KIM 1. Combined detection increased the AUC to 0.946, which was superior to either marker alone. Conclusion Urinary Netrin 1 and KIM 1 serve as sensitive and reliable biomarkers for the early prediction of renal injury induced by nucleoside/nucleotide analogs in patients with chronic hepatitis B. Combined detection improves predictive accuracy and supports early clinical intervention.

Key words: Chronic hepatitis B, Nucleoside/nucleotide analogs, Renal injury, Netrin-1, KIM-1, Predictive value

李宁, 吴妍, 张霄, 曹雷, 池洪治, 李庆禄. 尿Netrin-1及KIM-1水平对慢性乙型肝炎患者核苷(酸)类药物相关肾损伤的预测价值[J]. 肝脏, 2026, 31(7): 1015-1019.

Li Ning, Wu Yan, Zhang Xiao, Cao Lei, Chi Hongzhi, Li Qinglu. Predictive value of urinary Netrin-1 and KIM-1 for renal injury induced by nucleotide analogs in patients with chronic hepatitis B[J]. Chinese Hepatolgy, 2026, 31(7): 1015-1019.

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