Altered underlying renal tubular function in patients with chronic hepatitis B receiving nucleos(t)ide analogs in a real-world setting the MENTE study

Sonia Rodriguez-Novoa, Javier Garcia-Samaniego, Martin Prieto, Jose L. Calleja, Juan M. Pascasio, Manuel Delgado Blanco, Javier Crespo, Maria Buti, Maria L.Bonet Vidal, Juan Arenas Ruiz Tapiador, Conrado Fernandez-Rodriguez, Ricard Sola, Enrique Fraga, Luisa Gonzalez Dieguez, Oscar Nuñez, Manuel Praga, Javier Del PinoMontes, Manuel Romero-Gomez, Rosa Morillas, Moises DiagoAngeles Castro

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Abstract

© 2016 Wolters Kluwer Health, Inc. All rights reserved. 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.
Original languageEnglish
Pages (from-to)779-789
JournalJournal of Clinical Gastroenterology
Volume50
Issue number9
DOIs
Publication statusPublished - 1 Jan 2016

Keywords

  • Entecavir
  • Hepatitis B virus
  • Retinol-binding protein
  • Tenofovir
  • Tubular renal toxicity

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