Renal tubular dysfunction during long-term adefovir or tenofovir therapy in chronic hepatitis B
Article first published online: 16 APR 2012
Published 2012. This article is a US Government work and is in the public domain in the USA.
Alimentary Pharmacology & Therapeutics
Volume 35, Issue 11, pages 1317–1325, June 2012
How to Cite
Gara, N., Zhao, X., Collins, M. T., Chong, W. H., Kleiner, D. E., Jake Liang, T., Ghany, M. G. and Hoofnagle, J. H. (2012), Renal tubular dysfunction during long-term adefovir or tenofovir therapy in chronic hepatitis B. Alimentary Pharmacology & Therapeutics, 35: 1317–1325. doi: 10.1111/j.1365-2036.2012.05093.x
- Issue published online: 1 MAY 2012
- Article first published online: 16 APR 2012
- Manuscript Accepted: 22 MAR 2012
- Manuscript Revised: 16 MAR 2012
- Manuscript Revised: 13 MAR 2012
- Manuscript Received: 21 FEB 2012
- Intramural Divisions of the National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Dental and Craniofacial Research
- National Cancer Institute of the National Institutes of Health
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).
To assess the incidence of RTD during long-term nucleotide therapy of chronic hepatitis B.
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.
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.
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.