title: Resolution of adefovir-related nephrotoxicity by adefovir dose-reduction in patients with chronic hepatitis B.
abstract: BACKGROUND
  Chronic hepatitis B patients (CHB) treated with adefovir were followed up to evaluate nephrotoxicity and its outcome.
  
  
  OBJECTIVE
  To assess the incidence of renal dysfunction during adefovir therapy in Asian patients and factors associated with it, and evaluate strategies to improve adefovir-related renal dysfunction and their impact on viral suppression.
  
  
  METHODS
  Chronic hepatitis B clinic patients from a tertiary hospital on adefovir treatment, with their clinical and laboratory parameters were extracted from the hospital electronic clinical database in an observational study design. Patients were excluded if they had liver/renal transplant, baseline renal impairment or were on dialysis. Adefovir-related renal dysfunction was defined as adefovir-related abnormal serum creatinine (ARASC) > 125 μmol/L (males), >90 μmol/L (females); adefovir-related abnormal GFR <60 mL/min; and adefovir-related increased serum creatinine >0.5 mg/dL, without other known causes of nephrotoxicity.
  
  
  RESULTS
  A total of 271/383 adefovir-treated patients were suitable for analysis and 33(12%) patients developed abnormal serum creatinine. Cumulative increase in proportion of patients with ARASC was 33.8% and GFR ≤60 mL/min was 38.3% by 6 years, while serum creatinine increase ≥0.5 mg/dL was 21.48% by 5 years. Using multivariate analysis, the only independent baseline predictor of ARASC was GFR ≤76.1 mL/min. Patients who had ARASC had similar levels of viral suppression to those who did not have ARASC. Those who had ARASC either continued adefovir (24%), switched therapy (24%) or had adefovir dose reduction (52%). ARASC resolved and GFR normalised in almost all patients after either switching therapy or reducing adefovir dose, with no difference between the two strategies (P = 0.737). Those with adefovir dose reduction had no significant increase in HBV DNA (P = 0.170).
  
  
  CONCLUSIONS
  Adefovir-related renal dysfunction occurred in a significant number of adefovir-treated patients, but reduction of the dose led to renal improvement without compromising treatment efficacy.
authors: Department of Gastroenterology and Hepatology, National University of Singapore, Singapore.
authors: J L
authors: JL
authors: Hartono
authors: M O
authors: MO
authors: Aung
authors: Y Y
authors: YY
authors: Dan
authors: M
authors: M
authors: Gowans
authors: K
authors: K
authors: Lim
authors: Y M
authors: YM
authors: Lee
authors: G H
authors: GH
authors: Lee
authors: H C
authors: HC
authors: Low
authors: P S
authors: PS
authors: Tan
authors: M A
authors: MA
authors: Thwin
authors: C
authors: C
authors: Soon
authors: L-L
authors: LL
authors: Chiu
authors: M J
authors: MJ
authors: Khoo
authors: E
authors: E
authors: Koay
authors: S G
authors: SG
authors: Lim
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D044466:Asian People; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; C053001:adefovir; D003404:Creatinine; D000225:Adenine