Early kidney injury during long-term adefovir dipivoxil therapy for chronic hepatitis B

World J Gastroenterol. 2015 Mar 28;21(12):3657-62. doi: 10.3748/wjg.v21.i12.3657.

Abstract

Aim: To evaluate urine β2-microglobulin (β2-M), retinol-binding protein (RBP) excretion, and renal impairment with adefovir dipivoxil (ADV) for chronic hepatitis B.

Methods: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy (n = 90) or ADV plus lamivudine combination therapy (n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate (eGFR) at the initiation of antiviral therapy and every 6 mo for a period of five years.

Results: Urine β2-M abnormalities were observed in patients during the first (n = 3), second (n = 7), third (n = 11), fourth (n = 16), and fifth (n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first (n = 2), second (n = 8), third (n = 12), fourth (n = 15), and fifth (n = 22) year of ADV treatment. eGFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in eGFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and eGFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment.

Conclusion: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.

Keywords: Adefovir dipivoxil; Entecavir; Renal impairment; Retinol binding protein; Urine β2-microglobulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / physiopathology
  • Adenine / administration & dosage
  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects*
  • Biomarkers / blood
  • Biomarkers / urine
  • Case-Control Studies
  • Creatinine / blood
  • Drug Substitution
  • Female
  • Glomerular Filtration Rate
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Organophosphonates / administration & dosage
  • Organophosphonates / adverse effects*
  • Predictive Value of Tests
  • Prospective Studies
  • Retinol-Binding Proteins / urine
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • beta 2-Microglobulin / urine

Substances

  • Antiviral Agents
  • Biomarkers
  • Organophosphonates
  • Retinol-Binding Proteins
  • beta 2-Microglobulin
  • entecavir
  • Guanine
  • Creatinine
  • Adenine
  • adefovir dipivoxil