title: Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients.
abstract: BACKGROUND
  The efficacy of tenofovir disoproxil fumarate (TDF) as part of combination antiretroviral treatment (ART) has been demonstrated in several randomized, controlled trials. However, an increasing number of case reports suggest that TDF use may be associated with significant nephrotoxicity. Our objective was to determine the renal safety of TDF-containing ART regimens for HIV-infected individuals.
  
  
  METHODS
  MEDLINE, EMBASE, Global Health, Scopus, Biosis Previews, Cochrane Library, Web of Science, and existing systematic reviews were searched. Prospective studies comparing TDF-containing with non-TDF containing ART regimens were selected for inclusion. We extracted data on study characteristics, participant characteristics, therapeutic interventions, renal function, bone density, and fracture rates.
  
  
  RESULTS
  A total of 17 studies (including 9 randomized, controlled trials) met the selection criteria. Median sample size was 517 participants. Constituent ART regimens were diverse. There was a significantly greater loss of kidney function among the TDF recipients, compared with control subjects (mean difference in calculated creatinine clearance, 3.92 mL/min; 95% confidence interval [CI], 2.13-5.70 mL/min), as well as a greater risk of acute renal failure (risk difference, 0.7%; 95% CI, 0.2-1.2). There was no evidence that TDF use led to increased risk of severe proteinuria, hypophosphatemia, or fractures.
  
  
  CONCLUSIONS
  Although TDF use was associated with a statistically significant loss of renal function, the clinical magnitude of this effect was modest. Our findings do not support the need to restrict TDF use in jurisdictions where regular monitoring of renal function and serum phosphate levels is impractical.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Cooper
authors.forename: Natasha
authors.initials: N
authors.lastname: Wiebe
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Smith
authors.forename: Philip
authors.initials: P
authors.lastname: Keiser
authors.forename: Saraladevi
authors.initials: S
authors.lastname: Naicker
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonelli
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use*; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine