title: Tenofovir use and urinary biomarkers among HIV-infected women in the Women's Interagency HIV Study (WIHS).
abstract: BACKGROUND
  Tenofovir (TDF) has been associated with renal tubular injury. Biomarkers that signal early tubular dysfunction are needed because creatinine rise lags behind TDF-associated kidney dysfunction. We examined several urinary biomarkers to determine if rises accompanying TDF initiation preceded creatinine changes.
  
  
  METHODS
  Three urinary biomarkers of tubular impairment--neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and β-2-microglobulin (β2MG)--were measured across 3 time points (one pre-TDF visit and 2 post-TDF visits) in 132 HIV-positive women from the Women's Interagency HIV Study. Women initiating highly active antiretroviral therapy (HAART) containing TDF were propensity score matched to women initiating HAART without TDF and women not on HAART.
  
  
  RESULTS
  There were no differences between groups for NGAL or NAG, but β2MG was 19 times more likely to be elevated among TDF users at the second post-TDF visit compared with non-TDF users at the pre-TDF visit (P < 0.01). History of proteinuria was associated with elevated NGAL (P < 0.01). Factors associated with elevated NAG were glomerular filtration rate <60 mL/minute, history of proteinuria, hepatitis C (P < 0.01 for all), and diabetes mellitus (P = 0.05). Factors associated with increased odds of elevated β2MG were HIV RNA >100,000 copies/mL, hepatitis C, boosted protease inhibitor use, and glomerular filtration rate <60 mL/minute (P ≤ 0.01 for all).
  
  
  CONCLUSIONS
  β2MG levels are elevated in women on TDF, indicating probable early renal dysfunction. Biomarker elevation is additionally associated with baseline chronic kidney disease, uncontrolled viremia, and boosted protease inhibitor use. Future studies are needed to explore urinary biomarker thresholds in identifying treated HIV-infected individuals at risk for renal dysfunction.
authors.affiliation: *Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD †Department of Epidemiology, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD ‡Departments of Medicine, Epidemiology and Population Health, Montefiore Medical Center, Bronx, NY §Department of Medicine, State University of New York Health Science Center, Brooklyn, NY ‖Department of Medicine, Georgetown University Medical Center, Washington, DC ¶Department of Medicine, Division of Hematology, University of Southern California, Los Angeles, CA #Department of Medicine, University of California-San Francisco, San Francisco, CA **Department of Medicine, Cook County Hospital, Chicago, IL ††Department of Pharmacovigilance, Pharmaceutical Product Development, Morrisville, NC.
authors.forename: Ikwo
authors.initials: I
authors.lastname: Oboho
authors.forename: Alison G
authors.initials: AG
authors.lastname: Abraham
authors.forename: Lorie
authors.initials: L
authors.lastname: Benning
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Anjali
authors.initials: A
authors.lastname: Sharma
authors.forename: Mary
authors.initials: M
authors.lastname: Young
authors.forename: Pamela
authors.initials: P
authors.lastname: Burian
authors.forename: Monica
authors.initials: M
authors.lastname: Gandhi
authors.forename: Mardge
authors.initials: M
authors.lastname: Cohen
authors.forename: Lynda
authors.initials: L
authors.lastname: Szczech
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine*; D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D015415:Biomarkers / Q000652:urine*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000652:urine; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D000068698:Tenofovir; D001613:beta 2-Microglobulin / Q000652:urine*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D063065:Organophosphonates; D011518:Proto-Oncogene Proteins; D018894:Reverse Transcriptase Inhibitors; D001613:beta 2-Microglobulin; D000068698:Tenofovir; D000118:Acetylglucosaminidase; D000225:Adenine