title: Altered Underlying Renal Tubular Function in Patients With Chronic Hepatitis B Receiving Nucleos(t)ide Analogs in a Real-World Setting: The MENTE Study.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: *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.
authors.forename: Sonia
authors.initials: S
authors.lastname: Rodríguez-Nóvoa
authors.forename: Javier
authors.initials: J
authors.lastname: García-Samaniego
authors.forename: Martín
authors.initials: M
authors.lastname: Prieto
authors.forename: José L
authors.initials: JL
authors.lastname: Calleja
authors.forename: Juan M
authors.initials: JM
authors.lastname: Pascasio
authors.forename: Manuel
authors.initials: M
authors.lastname: Delgado Blanco
authors.forename: Javier
authors.initials: J
authors.lastname: Crespo
authors.forename: María
authors.initials: M
authors.lastname: Buti
authors.forename: Maria L
authors.initials: ML
authors.lastname: Bonet Vidal
authors.forename: Juan
authors.initials: J
authors.lastname: Arenas Ruiz Tapiador
authors.forename: Conrado
authors.initials: C
authors.lastname: Fernández-Rodríguez
authors.forename: Ricard
authors.initials: R
authors.lastname: Solá
authors.forename: Enrique
authors.initials: E
authors.lastname: Fraga
authors.forename: Luisa
authors.initials: L
authors.lastname: González Diéguez
authors.forename: Oscar
authors.initials: O
authors.lastname: Núñez
authors.forename: Manuel
authors.initials: M
authors.lastname: Praga
authors.forename: Javier
authors.initials: J
authors.lastname: Del Pino-Montes
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gómez
authors.forename: Rosa
authors.initials: R
authors.lastname: Morillas
authors.forename: Moisés
authors.initials: M
authors.lastname: Diago
authors.forename: Ángeles
authors.initials: Á
authors.lastname: Castro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003404:Creatinine / Q000652:urine; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000652:urine; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000009:adverse effects / Q000627:therapeutic use; D009711:Nucleotides / Q000009:adverse effects / Q000627:therapeutic use; D012177:Retinol-Binding Proteins / Q000652:urine; D012189:Retrospective Studies; D013030:Spain; D000068698:Tenofovir / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D009711:Nucleotides; D012177:Retinol-Binding Proteins; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir; D003404:Creatinine