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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).
AIM
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.

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  • Publisher Full Text
  • Authors

    Gara N, Zhao X, Collins MT, Chong WH, Kleiner DE, Jake Liang T, Ghany MG, Hoofnagle JH

    Institution

    Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA. naveen.gara@nih.gov

    Source

    Alimentary pharmacology & therapeutics 35:11 2012 Jun pg 1317-25

    MeSH

    Adenine
    Adult
    Aged
    Antiviral Agents
    Biological Markers
    Creatinine
    Female
    Glomerular Filtration Rate
    Hepatitis B, Chronic
    Humans
    Kidney Tubules
    Male
    Middle Aged
    Phosphates
    Phosphonic Acids
    Renal Insufficiency
    Time Factors
    Uric Acid

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Intramural

    Language

    eng

    PubMed ID

    22506503