title: Role of traditional risk factors and antiretroviral drugs in the incidence of chronic kidney disease, ANRS CO3 Aquitaine cohort, France, 2004-2012.
abstract: OBJECTIVE
  To examine the role of antiretroviral drugs (ART), HIV-related and traditional risk factors on the incidence of chronic kidney disease (CKD) in HIV-infected patients.
  
  
  METHODS
  Prospective hospital-based cohort of HIV-infected patients from 2004 to 2012.
  
  
  METHODS
  CKD was defined using MDRD equation as an estimated glomerular filtration rate (eGFR) less than 60 ml/mn/1.73 m(2) at 2 consecutive measurements ≥3 months apart. Poisson regression models were used to study determinants of CKD either measured at baseline or updated. ART exposure was classified as ever or never. We additionally tested the role of tenofovir (TDF), whether or not prescribed concomitantly with a Protease Inhibitor (PI), taking into account the cumulative exposure to the drug.
  
  
  RESULTS
  4,350 patients (74% men) with baseline eGFR>60 ml/mn/1.73 m(2) were followed for a median of 5.8 years. At the end of follow-up, 96% had received ART, one third of them (35%) jointly received TDF and a PI. Average incidence rate of CKD was 0.95% person-years of follow-up. Incidence of CKD was higher among women (IRR = 2.2), older patients (>60 y vs <45 y: IRR = 2.5 and 45-60 y: IRR = 1.7), those with diabetes (IRR = 1.9), high blood pressure (IRR = 1.5), hyperlipidemia (IRR = 1.5), AIDS stage (IRR = 1.4), low baseline eGFR (IRR = 15.8 for 60<eGFR<70 ml/mn/1.73 m(2) vs >90 and IRR = 7.1 for 70<eGFR<80 ml/mn/1.73 m(2)), current CD4+<200 cells/mm(3) vs >500/mm(3) (IRR = 2.5), and exposure to TDF (IRR = 2.0). Exposure to TDF was even strongly associated with CKD when co-administered with PIs (IRR = 3.1 vs 1.3 when not, p<0,001). A higher risk of CKD was found when tenofovir exposure was >12 months [IRR = 3.0 with joint PIs vs 1.3 without (p<0.001)]. A vast majority of those developing CKD (76.6%) had a baseline eGFR between 60 and 80 ml/mn/1.73 m(2).
  
  
  CONCLUSIONS
  In patients with eGFR between 60 and 80 mL/min/1.73 m(2), a thorough control of CKD risk factors is warranted. The use of TDF, especially when co-administered with PIs, should be mentioned as a relative contraindication in presence of at least one of these risk factors.
authors.affiliation: Univ. Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France. philippe.morlat@chu-bordeaux.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Morlat
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vivot
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Vandenhende
authors.forename: Frédéric-Antoine
authors.initials: FA
authors.lastname: Dauchy
authors.forename: Julien
authors.initials: J
authors.lastname: Asselineau
authors.forename: Edouard
authors.initials: E
authors.lastname: Déti
authors.forename: Yann
authors.initials: Y
authors.lastname: Gerard
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Lazaro
authors.forename: Pierre
authors.initials: P
authors.lastname: Duffau
authors.forename: Didier
authors.initials: D
authors.lastname: Neau
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bonnet
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives; D000367:Age Factors; D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D015331:Cohort Studies; D000075202:Contraindications; D005260:Female; D005602:France / Q000453:epidemiology; D005919:Glomerular Filtration Rate / Q000502:physiology; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects; D016012:Poisson Distribution; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000008:administration & dosage; D012044:Regression Analysis; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000209:etiology*; D012307:Risk Factors; D012737:Sex Factors; D000068698:Tenofovir
chemical_list: D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D011480:Protease Inhibitors; D000068698:Tenofovir; D000225:Adenine