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