title: Renal tubular dysfunction during long-term adefovir or tenofovir therapy in chronic hepatitis B.
abstract: BACKGROUND
  Adefovir and tenofovir are nucleotide analogues used as long-term therapy of chronic hepatitis B. Side effects are few, but prolonged and high-dose therapy has been associated with proximal renal tubular dysfunction (RTD).
  
  
  OBJECTIVE
  To assess the incidence of RTD during long-term nucleotide therapy of chronic hepatitis B.
  
  
  METHODS
  A total of 51 patients being treated at the Clinical Center, National Institutes of Health were studied. Diagnosis of RTD required de novo appearance of at least three of five features: hypophosphataemia, hypouricaemia, serum creatinine elevation, proteinuria or glucosuria.
  
  
  RESULTS
  Among 51 patients treated for 1-10 (mean 7.4) years with adefovir (n = 42), tenofovir (n = 4) or adefovir followed by tenofovir (n = 5), 7 (14%) developed RTD. Time to onset ranged from 22 to 94 (mean 49) months with an estimated 10-year cumulative rate of 15%. All seven had low urinary percent maximal tubular reabsorption of phosphate (<82%). Patients with RTD were older (58 vs. 44 years; P = 0.01) and had lower baseline glomerular filtration rates (82 vs. 97 cc/min; P = 0.08) compared to those without; but did not differ in other features. Six patients with RTD were switched to entecavir, all subsequently had improvements in serum phosphate (2.0-3.0 mg/dL), creatinine (1.6-1.1 mg/dL), uric acid (2.7-3.8 mg/dL) and proteinuria.
  
  
  CONCLUSIONS
  Renal tubular dysfunction develops in 15% of patients treated with adefovir or tenofovir for 2-9 years and is partially reversible with change to other antivirals. Monitoring for serum phosphate, creatinine and urinalysis is prudent during long-term adefovir and tenofovir therapy.
authors.affiliation: Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA. naveen.gara@nih.gov
authors.forename: N
authors.initials: N
authors.lastname: Gara
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: M T
authors.initials: MT
authors.lastname: Collins
authors.forename: W H
authors.initials: WH
authors.lastname: Chong
authors.forename: D E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: T
authors.initials: T
authors.lastname: Jake Liang
authors.forename: M G
authors.initials: MG
authors.lastname: Ghany
authors.forename: J H
authors.initials: JH
authors.lastname: Hoofnagle
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects*; D010710:Phosphates / Q000378:metabolism; D051437:Renal Insufficiency / Q000139:chemically induced*; D000068698:Tenofovir; D013997:Time Factors; D014527:Uric Acid / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D063065:Organophosphonates; D010710:Phosphates; D014527:Uric Acid; C053001:adefovir; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine