title: Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Kings College Hospital NHS Foundation Trust, London, UK; King's College London, London, UK. Electronic address: lisa.hamzah@kcl.ac.uk.
authors.forename: L
authors.initials: L
authors.lastname: Hamzah
authors.affiliation: University College London, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Jose
authors.affiliation: Royal Free Hospital NHS Foundation Trust, London, UK.
authors.forename: J W
authors.initials: JW
authors.lastname: Booth
authors.affiliation: St George's Healthcare NHS Trust, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Hegazi
authors.affiliation: Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Rayment
authors.affiliation: Imperial College Healthcare NHS Trust, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Bailey
authors.affiliation: Brighton and Sussex University Hospitals, Brighton, UK.
authors.forename: D I
authors.initials: DI
authors.lastname: Williams
authors.affiliation: King's College London, London, UK.
authors.forename: B M
authors.initials: BM
authors.lastname: Hendry
authors.affiliation: St George's Healthcare NHS Trust, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Hay
authors.affiliation: Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Jones
authors.affiliation: Imperial College Healthcare NHS Trust, London, UK.
authors.forename: J B
authors.initials: JB
authors.lastname: Levy
authors.affiliation: South Tees Hospital NHS Foundation Trust, Middlesbrough, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Chadwick
authors.affiliation: Royal Free Hospital NHS Foundation Trust, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Johnson
authors.affiliation: University College London, London, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Sabin
authors.affiliation: Kings College Hospital NHS Foundation Trust, London, UK.
authors.forename: F A
authors.initials: FA
authors.lastname: Post
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D000068698:Tenofovir / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir
keywords: Antiretroviral; Fanconi; HIV; Kidney; Renal; TDF; Tenofovir; Toxicity; Tubulopathy