title: Prevalence and significance of proximal renal tubular abnormalities in HIV-infected patients receiving tenofovir.
abstract: OBJECTIVE
  Patients receiving tenofovir, disoproxil, fumarate (TDF) had an increased prevalence of proximal renal tubular dysfunction (PRTD), but contributing factors and its clinical significance remain controversial.
  
  
  METHODS
  Cross-sectional evaluation of different urinary parameters (proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria) in 200 HIV-infected patients receiving TDF, 26 following TDF discontinuation, and 22 never treated with TDF, included in a prospective cohort study. PRTD was defined as two or more tubular abnormalities.
  
  
  RESULTS
  After a median of 65 months (interquartile range, 42.7-84.7), at least one tubular alteration was found in 72% of patients, mostly proteinuria (42, 50, and 14% in current, previous and never TDF use; P=0.02) and phosphaturia (46, 42, and 14%; respectively, P < 0.01). PRTD was found in 63 patients (32%) receiving TDF, ranging from 14 to 46% according to concomitant hepatitis C virus coinfection, diabetes mellitus or hypertension arterial, in contrast with six (23%) following TDF discontinuation, and zero cases in no TDF-treated patients. The use of TDF [odds ratio (OR) 13.2; 95% confidence interval (CI) 1.4-22.7; P = 0.01], cumulative time on combination antiretroviral therapy (OR 1.011; 95% CI 1.07-1.019 per month; P = 0.01), and baseline estimated glomerular filtration rate (eGFR, OR 0.97; 95% CI 0.94-0.99 per ml/min per 1.73 m higher; P = 0.04) were associated with PRTD. The number of tubular abnormalities was linearly associated with eGFR decline since TDF initiation (β-coefficient -0.15, P = 0.02), together with age (-0.18; P = 0.01), baseline eGFR (0.49, P = 0.01), diabetes mellitus (-0.19, P = 0.02), and time on TDF (-0.23; P = 0.01).
  
  
  CONCLUSIONS
  The use of TDF leads to an increased rate of tubular dysfunction, and modulated by age, baseline eGFR, and classical factors, is associated with kidney function decline.
authors.affiliation: aDepartment of Infectious Diseases bDepartment of Biochemistry cDepartment of Nephrology, Ramon y Cajal Hospital, Madrid, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Casado
authors.forename: Sara
authors.initials: S
authors.lastname: Bañón
authors.forename: Carmen
authors.initials: C
authors.lastname: Santiuste
authors.forename: Jorge
authors.initials: J
authors.lastname: Serna
authors.forename: Paula
authors.initials: P
authors.lastname: Guzman
authors.forename: Maite
authors.initials: M
authors.lastname: Tenorio
authors.forename: Fernando
authors.initials: F
authors.lastname: Liaño
authors.forename: José M
authors.initials: JM
authors.lastname: del Rey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000453:epidemiology* / Q000473:pathology; D007677:Kidney Function Tests; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D000068698:Tenofovir / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir