Effect of HBV polymerase inhibitors on renal function in patients with chronic hepatitis B

J Hepatol. 2011 Dec;55(6):1235-40. doi: 10.1016/j.jhep.2011.03.030. Epub 2011 May 19.

Abstract

Background & aims: Therapy of chronic hepatitis B with HBV-polymerase inhibitors, in particular tenofovir or adefovir, may affect renal function. To assess renal function more accurately in the normal range, we used the recently validated, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula to calculate the estimated glomerular filtration rate (eGFR).

Methods: Patient subgroups included: patients with HBV-monoinfection treated with lamivudine (n=36), adefovir (n=32), entecavir (n=32), or tenofovir (n=37). HBsAg-positive untreated patients (n=60) served as control. For comparison HIV-monoinfected patients treated with tenofovir (n=120) or zidovudine (n=52) based antiretroviral therapy and antiretroviral naive patients (n=109) were assessed. CKD-EPI equation was used to calculate eGFR. In a more sensitive approach, we modeled the individual change in eGFR over time with linear mixed effects models (LME).

Results: Yearly predicted median changes in individual eGFR according to the LME model were: HBV untreated -2.05 ml/min, HBV lamivudine -0.92 ml/min, HBV adefovir -1.02 ml/min, HBV entecavir -1.00 ml/min, and HBV tenofovir -0.92 ml/min (p<0.01 for HBV untreated vs. HBV treated). In HIV-monoinfected patients: HIV untreated -0.62 ml/min, HIV treated with tenofovir -2.64 ml/min, HIV treated with zidovudine -1.0 ml/min (p=0.017 for tenofovir vs. no treatment, p<0.001 for tenofovir vs. zidovudine).

Conclusions: Therapy of HBV infection irrespective of medication seems to result in a milder decrease of renal function. In contrast tenofovir as part of HIV combination therapy seems to impair renal function in this Caucasian population.

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives
  • Adenine / therapeutic use
  • Adolescent
  • Adult
  • Aged
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use
  • Case-Control Studies
  • Female
  • Gene Products, pol / antagonists & inhibitors*
  • Glomerular Filtration Rate / drug effects*
  • HIV Infections / drug therapy
  • HIV Infections / physiopathology
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / physiopathology*
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Organophosphonates / adverse effects
  • Organophosphonates / therapeutic use
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Tenofovir
  • Young Adult

Substances

  • Anti-HIV Agents
  • Antiviral Agents
  • Gene Products, pol
  • Organophosphonates
  • P protein, Hepatitis B virus
  • Reverse Transcriptase Inhibitors
  • Tenofovir
  • Adenine