Related Experiment Video
Updated: Mar 19, 2026
A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
Altered Underlying Renal Tubular Function in Patients With Chronic Hepatitis B Receiving Nucleos(t)ide Analogs in a
Sonia Rodríguez-Nóvoa1, Javier García-Samaniego, Martín Prieto
1*Genetic of Metabolic Diseases Laboratory, Institute of Medical and Molecular Genetics (INGEMM), Madrid †Department of Hepatology, Hospital Universitario La Paz/Carlos III, CIBEREHD §Department of Hepatology, Hosp. Puerta de Hierro-Majadahonda, Universidad Autónoma de Madrid, CIBEREHD §§Department of Digestive Diseases, Hosp. de Alcorcón ***Department of Digestive Diseases, Hosp. Infanta Sofía †††Department of Nephrology, Hosp. 12 Octubre, Madrid ‡Digestive Medicine Service, Hospital Universitari i Politécnic La Fe, and CIBEREHD ¶¶¶Department of Digestive Diseases, Hosp. General de Valencia, Valencia ∥Department of Digestive Diseases, Hosp. Virgen del Rocío, IBIS, CIBEREHD §§§Department of Digestive Diseases, Hosp. de Valme, CIBEREHD, Sevilla ¶Departament of Digestive Disease, Hospital Universitario La Coruña ###División of Clinical Virology, INIBIC-Complejo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña, A Coruña #Gastroenterology and Hepatology Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander **Department of Hepatology, Hosp. Univ. Vall d´Hebrón, CIBEREHD ∥∥Liver Section, Hospital del Mar. IMIM. Universitat Autónoma de Barcelona, Barcelona ††Hosp. Univ. Son Espases, Palma de Mallorca ‡‡Department of Digestive Diseases, Hosp. Univ. Donostia, Donostia ¶¶Department of Digestive Diseases, Hosp. Reina Sofía, Córdoba ##Department of Hepatology, Hospital Universitario Central de Asturias, Oviedo ‡‡‡Department of Reumathology, Hosp. Univ. Salamanca, Salamanca ∥∥∥CIBEREHD and Hepatology Unit, Hospital Germans Trias i Pujol, Badalona, Spain.
Background:
Cases of renal tubular dysfunction have been reported in patients with hepatitis B and in patients with human immunodeficiency virus who are undergoing tenofovir treatment. However, little is known about the impact on tubular function in patients with chronic hepatitis B (CHB) under long-term use of entecavir (ETV) and tenofovir disoproxil fumarate (TDF). We evaluated markers of renal tubular function and bone turnover in patients with CHB treated with ETV or TDF.
Patients And Methods:
A multicenter, cross-sectional study was performed on markers of renal tubular function and bone turnover in hepatitis B virus-monoinfected patients on long-term treatment with Entecavir or Tenofovir (the MENTE study). The analyzed parameters were: retinol-binding protein/creatinine, neutrophil gelatinase-associated lipocalin/creatinine, excretion of phosphates, uric acid excretion, glomerular filtrate, protein/creatinine, albumin/creatinine, serum creatinine, phosphate, CTX, P1NP, vitamin D, and parathormone.
Results:
A total of 280 patients (ETV: 89, TDF: 69, control: 122) were included in this study. The TDF group was associated with altered levels of retinol-binding protein (RBP)/creatinine (TDF 25% vs. 7% ETV and control; P<0.001). Protein/creatinine, uric acid excretion, P1NP1, and parathormone were higher in the TDF group. The proportion of patients with serum phosphate <2.5 mg/dL was higher in both the ETV and the TDF groups compared with the control. The multivariate analysis showed that the use of TDF was independently associated with a higher risk of altered excretion of RBP/creatinine (4.4; interquartile range: 1.4 to 14; P=0.013).
Conclusions:
We found an independent association between TDF use and altered RBP excretion. This finding indicates subclinical tubular damage. Because tubular dysfunction can precede the decline of renal function, close monitoring of RBP levels in patients with CHB on nucleos(t)ide analog treatment must be performed for early detection of TDF-related renal toxicity. In this study, these differences in tubular function were not associated with concomitant changes in markers of bone turnover.
Related Concept Videos
01:22Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
01:26Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
01:11Renal Failure: Dose Adjustments
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
01:14Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug
01:25Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase