title: Proteinuria is associated with neurocognitive impairment in antiretroviral therapy treated HIV-infected individuals.
abstract: BACKGROUND
  Proteinuria is a marker of vascular dysfunction that predicted increased cardiovascular mortality and is associated with neurocognitive impairment (NCI) in population-based studies. We examined associations between proteinuria and HIV-associated NCI.
  
  
  METHODS
  Multivariable logistic regression was used to examine associations between NCI at the first neurocognitive assessment (baseline) and simultaneous, clinically significant proteinuria [as random spot urine protein-to-creatinine ratios (UP/Cr) ≥200 mg/g] in a prospective multicenter observational cohort study. Generalized estimating equations were used to examine associations between baseline proteinuria and subsequent NCI among subjects without NCI at baseline. NCI was defined as a Z-score, derived from the combination of normalized scores from the Trailmaking A and B and the Wechsler Adult Intelligence Scale-Revised Digit Symbol tests.
  
  
  RESULTS
  A total of 1972 subjects were included in this analysis. Baseline proteinuria was associated with increased odds of NCI [odds ratio (OR): 1.41, 95% confidence interval (CI): 1.08 to 1.85; P = 0.01] and with subsequent NCI among subjects without NCI at baseline (OR: 1.39, 95% CI: 1.01 to 1.93; P = 0.046) in multivariable models adjusted for risk factors and potential confounders. Similar associations were evident when these analyses were limited to visits at which time study subjects maintained plasma HIV RNA levels <200 copies per milliliter.
  
  
  CONCLUSIONS
  The association between proteinuria and NCI observed in this study adds to a growing body of evidence implicating contributions by vascular disease to NCI in antiretroviral treated individuals. Studies examining interventions that improve vascular function are warranted.
authors.affiliation: *Department of Medicine, MetroHealth Medical Center; Cleveland, OH; †Geriatric Research Education and Clinical Centers, Louis Stokes Cleveland Veterans Administration, Cleveland, OH; ‡Statistical and Data Analysis Center, Harvard School of Public Health; Boston, MA; §Department of Neurology and Neurological Surgery, Washington University of St. Louis, St. Louis, MO; ‖UCLA CARE Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; and ¶Department of Epidemiology, Milken Institute School of Public Health, George Washington University, Washington, DC.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kalayjian
authors.forename: Kunling
authors.initials: K
authors.lastname: Wu
authors.forename: Scott
authors.initials: S
authors.lastname: Evans
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.forename: Muraldihar
authors.initials: M
authors.lastname: Pallaki
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
authors.forename: Marlene
authors.initials: M
authors.lastname: Smryzynski
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D060825:Cognitive Dysfunction / Q000652:urine* / Q000821:virology*; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000188:drug therapy / Q000523:psychology / Q000652:urine*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D011446:Prospective Studies; D011507:Proteinuria / Q000523:psychology / Q000821:virology*; D011795:Surveys and Questionnaires
chemical_list: D019380:Anti-HIV Agents