title: Brief Report: Cumulative Tenofovir Disoproxil Fumarate Exposure is Associated With Biomarkers of Tubular Injury and Fibrosis in HIV-Infected Men.
abstract: Tenofovir disoproxil fumarate (TDF) can cause kidney damage, but current clinical tests are insensitive for detecting toxicity. Among 884 HIV-infected men enrolled in the Multicenter AIDS Cohort Study, we measured urine biomarkers specific for tubular damage (interleukin-18, kidney injury molecule-1, procollagen type III N-terminal propeptide) and albuminuria. In adjusted analyses, each year of TDF exposure was independently associated with 3.3% higher interleukin-18 (95% CI: 0.8% to 5.8%), 3.4% higher kidney injury molecule-1 (1.1% to 5.7%), and 3.1% higher procollagen type III N-terminal propeptide (0.8% to 5.5%), but not with albuminuria (2.8%; -0.6% to 6.2%). Biomarkers of tubular damage may be more sensitive than albuminuria for detecting toxicity from TDF and other medications.
authors.affiliation: *Department of Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, CA; †Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA; ‡Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD; §Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; ‖Division of HIV Medicine, Department of Medicine, Harbor-UCLA Medical Center and the Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA; ¶Division of Infectious Diseases, Department of Medicine, Northwestern University, Chicago, IL; #Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA; **Department of Medicine, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; ††Section of Nephrology, Department of Medicine, Yale University, New Haven, CT; ‡‡Department of Medicine, Program of Applied Translational Research, Yale University, New Haven, CT; §§Division of Nephrology-Hypertension, Department of Medicine, University of California, San Diego, CA; and ‖‖Department of Medicine, Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA.
authors.forename: Vasantha
authors.initials: V
authors.lastname: Jotwani
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Estrella
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Mallory D
authors.initials: MD
authors.lastname: Witt
authors.forename: Frank
authors.initials: F
authors.lastname: Palella
authors.forename: Bernard
authors.initials: B
authors.lastname: Macatangay
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.forename: Michael
authors.initials: M
authors.lastname: Shlipak
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D005355:Fibrosis / Q000139:chemically induced*; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D000068698:Tenofovir / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D015415:Biomarkers; D000068698:Tenofovir