BACKGROUNDPatients with chronic hepatitis B (CHB) with long-term nucleos(t)ide therapy may experience renal insufficiency. Traditional renal function indicators, such as urine protein, serum urea nitrogen (BUN), and serum creatinine, are normal when early mild lesions occur. Therefore, more sensitive renal function indicators are needed.AIMTo investigate the significance of early renal injury indicators in evaluating renal injury in patients with CHB with long-term nucleos(t)ide therapy.METHODSWe collected the clinical data of 69 outpatients with CHB at Peking University First Hospital from March 2018 to January 2020 who had been treated with long-term nucleos(t)ide therapy and analyzed the results of early renal injury indicators. Continuous normal distribution data were analyzed by the t-test to determine the difference between two groups. Continuous non-normally distributed data were analyzed by the Mann-Whitney U-test between two groups. The Kruskal-Wallis H test was used to determine the differences among multiple groups. Enumeration data were analyzed by the chi-square test. The related factors of early renal injury indicators were analyzed by logistic regression analysis.RESULTSThe average treatment duration with nucleos(t)ide analogs of the 69 patients with CHB was 99.7 ± 28.7 mo. The cases of patients with elevated BUN and hypophosphatemia were 6 (8.7%) and 13 (18.8%), respectively; 31 (44.9%) patients had abnormal early renal injury indicators, including 9 patients with abnormal urine microalbumin, 7 patients with abnormal urine immunoglobulin, 6 patients with abnormal urine transferrin, and 19 patients with abnormal α1 microglobulin. There were no significant differences in the mean values of age, sex, BUN, estimated glomerular filtration rate (eGFR), serum uric acid, serum calcium, or serum phosphorus between the two groups of patients with and without early renal injury indicators. However, the mean levels of serum creatinine and urine creatinine, N-acetyl-β-D-glucosidase enzyme, α1 microglobulin, and urine immunoglobulin in the former group of patients were significantly higher than those in the latter group of patients (P < 0.05). The incidence of early renal injury in patients with eGFR ≥ 90, 60-89, and 30-59 mL/(min·1.73 m2) was 36.4% (8/22), 47.6% (20/42), and 60% (3/5), respectively. Logistic regression analysis results showed that gamma-glutamyl transpeptidase [odds ratio (OR) = 1.05 (1.008-1.093), P = 0.020], direct bilirubin [OR = 1.548 (1.111-2.159), P = 0.010], serum creatinine [OR = 1.079 (1.022-1.139), P = 0.006], and age [OR = 0.981 (0.942-1.022), P = 0.357] were independent predictors of early renal injury.CONCLUSIONPatients with CHB treated with long-term nucleos(t)ide analog therapy had a high probability of early renal injury, and early renal injury indicators were highly sensitive and could be used to monitor early renal impairment.