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Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate

Hamzah, L; Jose, S; Booth, JW; Hegazi, A; Rayment, M; Bailey, A; Williams, DI; ... Post, FA; + view all (2017) Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate. Journal of Infection , 74 (5) pp. 492-500. 10.1016/j.jinf.2017.01.010. Green open access

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Abstract

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) is widely used in the treatment or prevention of HIV and hepatitis B infection. TDF may cause renal tubulopathy in a small proportion of recipients. We aimed to study the risk factors for developing severe renal tubulopathy. METHODS: We conducted an observational cohort study with retrospective identification of cases of treatment-limiting tubulopathy during TDF exposure. We used multivariate Poisson regression analysis to identify risk factors for tubulopathy, and mixed effects models to analyse adjusted estimated glomerular filtration rate (eGFR) slopes. RESULTS: Between October 2002 and June 2013, 60 (0.4%) of 15,983 patients who had received TDF developed tubulopathy after a median exposure of 44.1 (IQR 20.4, 64.4) months. Tubulopathy cases were predominantly male (92%), of white ethnicity (93%), and exposed to antiretroviral regimens that contained boosted protease inhibitors (PI, 90%). In multivariate analysis, age, ethnicity, CD4 cell count and use of didanosine or PI were significantly associated with tubulopathy. Tubulopathy cases experienced significantly greater eGFR decline while receiving TDF than the comparator group (−6.60 [−7.70, −5.50] vs. −0.34 [−0.43, −0.26] mL/min/1.73 m2/year, p < 0.0001). CONCLUSIONS: Older age, white ethnicity, immunodeficiency and co-administration of ddI and PI were risk factors for tubulopathy in patients who received TDF-containing antiretroviral therapy. The presence of rapid eGFR decline identified TDF recipients at increased risk of tubulopathy.

Type: Article
Title: Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jinf.2017.01.010
Publisher version: http://doi.org/10.1016/j.jinf.2017.01.010
Language: English
Additional information: © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Infectious Diseases, HIV, Tubulopathy, Fanconi, Renal, Kidney, Antiretroviral, Toxicity, Tenofovir, TDF, CHRONIC KIDNEY-DISEASE, HIV-INFECTED PATIENTS, NEPHROGENIC DIABETES-INSIPIDUS, FANCONI-SYNDROME, TUBULAR DYSFUNCTION, POSITIVE PATIENTS, MITOCHONDRIAL TOXICITY, RECEIVING TENOFOVIR, DIDANOSINE THERAPY, INITIAL TREATMENT
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health > Infection and Population Health
URI: http://discovery.ucl.ac.uk/id/eprint/10043273
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