title: Relationship between renal dysfunction, nephrotoxicity and death among HIV adults on tenofovir.
abstract: OBJECTIVE
  In April 2010, the South African government added tenofovir disoproxil fumarate to its first-line antiretroviral therapy (ART) for HIV patients. We analyzed the relationship between renal dysfunction at tenofovir initiation, nephrotoxicity and mortality.
  
  
  METHODS
  Cohort analysis of HIV-infected adults who received tenofovir and had a creatinine clearance done at initiation at the Themba Lethu Clinic, Johannesburg, South Africa, between April 2004 and September 2009.
  
  
  METHODS
  We estimated the relationship between renal dysfunction, nephrotoxicity [any decline in kidney function from baseline (acute or chronic) that is secondary to a toxin (including drugs)] and mortality for patients initiated onto tenofovir-containing regimens using marginal structural models and inverse probability of treatment weights to correct estimates for lost to follow-up and confounding.
  
  
  RESULTS
  Of 890 patients initiated onto tenofovir, 573 (64.4%) had normal renal function (≥90 ml/min), 271 (30.4%) had mild renal dysfunction (60-89 ml/min) and 46 (5.2%) had moderate renal dysfunction (30-59 ml/min). A total of 2.4% experienced nephrotoxicity, 7.8% died and 9.7% were lost during 48 months of follow-up. Patients with mild [hazard ratio 4.8; 95% confidence interval (CI) 1.5-15.2] or moderate (hazard ratio 15.0; 95% CI 3.4-66.5) renal dysfunction were at greatest risk of nephrotoxicity, whereas those with mild (hazard ratio 1.2; 95% CI 0.7-2.3) or moderate (hazard ratio 3.2; 95% CI 1.3-7.8) renal dysfunction vs. normal renal function were at highest risk of death by 48 months.
  
  
  CONCLUSIONS
  Much of the incident renal dysfunction in tenofovir patients is likely related to preexisting renal disorder, which may be exacerbated by tenofovir. With expanded use of tenofovir, screening for renal dysfunction prior to initiation and dose adjustment is necessary to help improve ART outcomes.
authors.affiliation: Center for Global Health and Development, Boston University, Massachusetts, USA. abrennan@bu.edu
authors.forename: Alana
authors.initials: A
authors.lastname: Brennan
authors.forename: Denise
authors.initials: D
authors.lastname: Evans
authors.forename: Mhairi
authors.initials: M
authors.lastname: Maskew
authors.forename: Saraladevi
authors.initials: S
authors.lastname: Naicker
authors.forename: Prudence
authors.initials: P
authors.lastname: Ive
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
authors.forename: Thapelo
authors.initials: T
authors.lastname: Maotoe
authors.forename: Matthew
authors.initials: M
authors.lastname: Fox
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects*; D051437:Renal Insufficiency / Q000139:chemically induced / Q000401:mortality; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine