Frequency and risk factors of renal impairment during long-term adefovir dipivoxil treatment in chronic hepatitis B patients

Background and Aim: There are insufficient data on renal safety during long-term adefovir dipivoxil (ADV) treatment. We aimed to elucidate the incidence and risk factors of renal impairment in chronic hepatitis B (CHB) patients treated with ADV. Methods: We retrospectively enrolled 687 CHB patients (51.4% with compensated cirrhosis) treated with ADV alone (18.2%) or in combination with lamivudine (81.8%) for more than 12months. Renal function was measured using the estimated glomerular filtration rate (eGFR), and renal dysfunction was defined as mild (20-30% decrease), moderate (30-50%), or severe (more than 50%). Results: During the median treatment duration of 27months, 72 patients (10.5%) developed renal impairment, which was mild in 77.8% of cases, moderate in 20.8% of cases, and severe in one patient. The cumulative incidence of renal impairment at 1, 3, and 5years was 2.6%, 14.8%, and 34.7%, respectively. Modification of the dosing interval or discontinuation of ADV was required in seven and three patients, respectively, and none of them showed a further decline in the eGFR. Although a univariate analysis revealed age, the number of exposure to radio-contrast dye, liver cirrhosis, and hepatocellular carcinoma as risk factors of renal impairment, age was the only significant risk factor identified in the multivariate analysis (odds ratio=1.048, 95% confidence interval=1.019-1.076, P=0.001). Conclusions: Renal impairment in long-term ADV users was relatively frequent, but serious renal toxicity was rare, and all cases were safely managed. Careful monitoring of renal function is required, especially in older patients.