title: Tenofovir clearance is reduced in HIV-positive patients with subclinical tubular impairment.
abstract: OBJECTIVE
  To assess if tenofovir (TFV) clearance is associated with urinary retinal-binding protein (RBP) in HIV-positive patients with normal estimated filtration rate.
  
  
  METHODS
  A cross-sectional diagnostic study.
  
  
  METHODS
  HIV-positive patients with estimated creatinine clearance above 60 ml/min, on tenofovir disoproxil fumarate (TDF)-containing combination since at least 6 months, taking TDF at night, and without significant comorbidities (diabetes, untreated hypertension, known renal malformations, recurrent nephrolithiasis) and nephrotoxic drugs were included. TFV plasma and urinary concentrations were measured 12 h after drug intake (C12). RBP was measured through enzyme immunoassay kit on spot urines and corrected per urinary creatinine (uRBP/uCr); normality ranges were below 130 μg/g (in patients aged <50 years) and below 172 μg/g (in patients aged ≥50 years).
  
  
  RESULTS
  Two hundred and eighty-nine patients were included (median age of 45.8 years, 71.6% male and 85.4% whites); patients were concomitantly treated with nonnucleoside reverse transcriptase inhibitors (155, 53.6%), protease inhibitors (118, 40.8%), or integrase inhibitors (16, 5.5%)-containing regimens. Estimated creatinine clearance was 89.4 ml/min (78.6-105.9). Urinary RBP (uRBP) and uRBP/uCr were 204.6 ng/ml (92-380) and 169.7 μg/g (85.8-318.3), respectively; abnormally high uRBP/uCr was observed in 157 patients (54.3%). A multivariate binary logistic regression confirmed that both ethnicity (P = 0.004, β 2.93, 95% confidence interval 1.41-6.10) and TFV urinary C12 less than 21 mg/ml (P = 0.006, β 2.04, 95% confidence interval 1.12-3.41) were significantly associated with abnormal uRBP/uCr.
  
  
  CONCLUSIONS
  HIV-positive TDF-treated patients showed a high prevalence of proximal tubular impairment: ethnicity (whites) and low urinary TFV concentrations were significantly associated with elevated uRBP. SDC VIDEO:: http://links.lww.com/QAD/A852.
authors.affiliation: aUnit of Infectious Diseases, Department of Medical Sciences, University of Torino bLaboratory of Clinical Biochemistry, AOU Città Della Salute e Della Scienza, Torino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calcagno
authors.forename: Jessica
authors.initials: J
authors.lastname: Cusato
authors.forename: Letizia
authors.initials: L
authors.lastname: Marinaro
authors.forename: Marco
authors.initials: M
authors.lastname: Simiele
authors.forename: Manuela
authors.initials: M
authors.lastname: Lucchiari
authors.forename: Chiara
authors.initials: C
authors.lastname: Alcantarini
authors.forename: Maria C
authors.initials: MC
authors.lastname: Tettoni
authors.forename: Laura
authors.initials: L
authors.lastname: Trentini
authors.forename: Giulio
authors.initials: G
authors.lastname: Mengozzi
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D058070:Asymptomatic Diseases; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D051437:Renal Insufficiency / Q000473:pathology*; D000068698:Tenofovir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014556:Urine / Q000737:chemistry
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir