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Proteinuria is Associated With Neurocognitive Impairment in Antiretroviral Therapy Treated HIV-Infected Individuals

Kalayjian, Robert C. MD*,§; Wu, Kunling MS; Evans, Scott PhD, MS; Clifford, David B. MD; Pallaki, Muraldihar MD§; Currier, Judith S. MD, MSc; Smryzynski, Marlene PhD, MSPH†,¶

JAIDS Journal of Acquired Immune Deficiency Syndromes: September 1st, 2014 - Volume 67 - Issue 1 - p 30–35
doi: 10.1097/QAI.0000000000000237
Clinical Science

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.

*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.

Correspondence to: Robert C. Kalayjian, MD, Division of Infectious Diseases, 2500 MetroHealth Drive, Cleveland, OH 44108 (e-mail:

Supported by NIH AI 069501, AI 036219, AI 069424 and the Veterans Administration: VISN10 Geriatric Research Education and Clinical Centers, Louis Stokes Cleveland Veterans Administration Medical Center.

D.B.C. serves a consultant for Biogen, Idec, Millennium, Bristol Myers Squibb, Pfizer, Genzyme, Amgen, Quintiles, Genetech, and AstraZeneca and received honoraria for lectures from Sun Biopharma; R.C.K. is currently receiving a grant from Gilead (GS-US-292-0112). The other authors have no conflicts of interest to disclose.

Presented at the 20th Conference on Retroviruses and Opportunistic Infections, 2013, March 6, 2013. Atlanta, GA, Abstract No. 460.

Received February 12, 2014

Accepted May 01, 2014

© 2014 by Lippincott Williams & Wilkins