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Proteinuria Is Associated With Increased Risk of Fragility Fracture in Men With or at Risk of HIV Infection

Gonciulea, Anda MDa; Wang, Ruibin MSb; Althoff, Keri N. PhDb; Estrella, Michelle M. MDc; Sellmeyer, Deborah E. MDd; Palella, Frank J. MDe; Lake, Jordan E. MD, MScf; Kingsley, Lawrence A. DrPHg; Brown, Todd T. MD, PhDa

JAIDS Journal of Acquired Immune Deficiency Syndromes: July 1, 2019 - Volume 81 - Issue 3 - p e85–e91
doi: 10.1097/QAI.0000000000002039
Clinical Science
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Background: Proteinuria has been associated with bone loss and fractures in general population, but data in HIV-infected population are lacking.

Setting: Prospective, multicenter cohort study of men with or at risk of HIV infection.

Methods: Between 2006 and 2015, urine protein measurements and bone fracture histories were ascertained semiannually in 947 HIV-infected (HIV+) and 969 HIV-uninfected (HIV−) men aged 40 years or older. Proteinuria was defined as protein-to-creatinine ratio ≥200 mg/g at ≥2 consecutive visits. Outcome measures (1) all fractures (excluding fractures of skull, face, and digits) and (2) fragility fractures (fractures of vertebral column, femur, wrist, and humerus). Multivariable Cox proportional hazards models assessed the association between proteinuria and fracture after adjusting for additional risk factors.

Results: The overall period prevalence of proteinuria was higher among HIV+ than HIV− (29% vs 6%, P < 0.001). Men with proteinuria had a significantly higher risk of fragility fracture compared with men without proteinuria [adjusted hazard ratio (aHR) = 2.29 (1.12–4.66)] and did not differ by HIV serostatus (p-interaction = 0.83). The risk of all fractures was not statistically different between men with or without proteinuria [aHR = 1.31 (0.84–2.05)]. Among HIV+ men, the association between confirmed proteinuria and fragility fracture was attenuated [aHR = 2.12 (0.95–4.73)] after additional adjustment for CD4+ T-cell count/mm3, history of AIDS, the presence of detectable plasma HIV-1 RNA, and cumulative exposure to tenofovir disoproxil fumarate.

Conclusions: Proteinuria was more common in HIV+ than in HIV− men and was a strong independent risk factor for fragility fracture regardless of HIV serostatus. Proteinuria should prompt consideration of a thorough evaluation for bone disease among HIV+ persons.

aDivision of Endocrinology, Diabetes, and Metabolism, Johns Hopkins, University, Baltimore, MD;

bDepartment of Epidemiology, Johns Hopkins University, Baltimore, MD;

cKidney Health Research Collaborative, San Francisco VA Health Science Center, University of California, San Francisco, San Francisco, CA;

dDivision of Endocrinology, Gerontology, and Metabolism, Stanford University, Palo Alto, CA;

eDivision of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL;

fDivision of Infectious Diseases, McGovern Medical School, University of Texas Health Science Center, Houston, TX; and

gDepartment of Infectious Diseases and Microbiology, University of Pittsburgh School of Public Health, Pittsburgh, PA.

Correspondence to: Todd T. Brown, MD, PhD, 1830 East Monument Street, Suite 333, Baltimore, MD 21287 (e-mail: tbrown27@jhmi.edu).

J.E.L. has received funding from the National Institutes of Health, National Institute of Allergy and Infectious Diseases (K23 AI110532). T.T.B. has received funding from the National Institutes of Health, National Institute of Allergy and Infectious Diseases (K24 AI120834; R01 AI093520). A.G. received support from the Clinical Research and Epidemiology in Diabetes and Endocrinology Training Grant T32DK062707. K.N.A. has received funding from the National Institutes of Health, National Institute of Allergy and Infectious Diseases (K01AI093197) and the National Institute on Aging (R01 AG053100). Data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS). MACS (Principal Investigators): Johns Hopkins University Bloomberg School of Public Health (Joseph Margolick/Todd Brown), U01-AI35042; Northwestern University (Steven Wolinsky), U01-AI35039; University of California, Los Angeles (Roger Detels/Oto Martinez-Maza), U01-AI35040; University of Pittsburgh (Charles Rinaldo), U01-AI35041; the Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson/Gypsyamber D'Souza), UM1-AI35043. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR001079 (JHU ICTR) from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The research was also supported by the HIV Prevention Trials Network (HPTN) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and the Office of AIDS Research, of the National Institutes of Health (NIH), Dept. of Health and Human Services (DHHS) (UM1 AI068613). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH), Johns Hopkins ICTR, or NCATS. The MACS website is located at http://aidscohortstudy.org/.

Presented at the Endocrine Society Meeting; April 2, 2016; Boston, MA.

J.E.L. has served as a consultant for Gilead Sciences, Merck, and GSK. T.T.B. has served as a consultant to Gilead Sciences, ViiV Healthcare, Merck, Theratechnologies, EMD-Serono, and Bristol Myers Squibb. F.J.P. has served as a consultant and on the Speakers Bureau for Gilead Sciences Janssen Pharmaceuticals, Merck and Co and Bristol Meyers Squibb. K.N.A. has served as a consultant to Trio Health. The remaining authors have no conflicts of interest to disclose.

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Received October 22, 2018

Accepted February 13, 2019

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