Neutrophil gelatinase-associated lipocalin accurately predicts renal tubular injury in patients with chronic hepatitis B treated with nucleos(t)ide analogs

Hepatol Res. 2018 Feb;48(2):144-152. doi: 10.1111/hepr.12908. Epub 2017 Jun 29.

Abstract

Aim: Little is known about the impact of long-term use of nucleos(t)ide analogs on tubular function in patients with chronic hepatitis B. Previous studies showed that neutrophil gelatinase-associated lipocalin (NGAL) elevation was associated with renal tubular injury. We evaluated renal function markers and bone mineral density in patients treated long-term with adefovir dipivoxil (ADV) or entecavir (ETV).

Methods: In this cross-sectional study, we enrolled 78 patients (ADV, 36; ETV: 42), and 21 patients matched for age, observation time, and baseline estimated glomerular filtration rate from each group.

Results: Patients treated with ADV showed a significant increase in serum creatinine and urine β2 -microglobulin, and decreased estimated glomerular filtration rate and bone mineral density. Furthermore, the median levels of NGAL in patients treated with ADV were significantly higher than those of ETV (12.5 ng/mL vs. 2.5 ng/mL, P = 0.020). The proportions of patients with proteinuria and phosphate <1 mmol/L in the ADV group were higher than those in the ETV group. Additionally, age, β2 -microglobulin, phosphate, and ADV use were associated with altered NGAL levels on multivariate analysis. Among the commonly used biomarkers, NGAL was the most useful (odds ratio = 5.72; P = 0.005) and specific (92% specificity at 18.1 ng/mL cut-off) in predicting low bone mass.

Conclusions: Patients with chronic hepatitis B treated long-term with ADV showed elevated urinary NGAL levels. Neutrophil gelatinase-associated lipocalin was more specific in predicting low bone mass during therapy compared with β2 -microglobulin, phosphate, and creatinine. In general, this analysis examined the value of NGAL as a renal tubular injury indicator, resulting from ADV use.

Keywords: adefovir dipivoxil; chronic hepatitis B; entecavir; neutrophil gelatinase-associated lipocalin; renal tubular injury.