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Longitudinal Assessment of Proximal Tubular Dysfunction in HIV Seropositive and Seronegative Persons: Correlates and Implications

Sheets, Kerry M. MD*; Atta, Mohamed G. MD; Fine, Derek M. MD; Zook, Katie BA; Mcfall, Allison M. MHS§; Estrella, Michelle M. MD, MHS; Schwartz, George J. MD; Lucas, Gregory M. MD, PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: May 1st, 2017 - Volume 75 - Issue 1 - p 45–51
doi: 10.1097/QAI.0000000000001302
Clinical Science

Background: Proximal tubular dysfunction (PTD) is common in HIV-positive persons and has been associated with tenofovir disoproxil fumarate (TDF). However, few studies have assessed the natural history PTD in HIV-positive and -negative individuals, or the association of PTD with the subsequent trajectory of directly measured glomerular filtration rate (mGFR).

Methods: We followed 192 HIV-positive and 100 HIV-negative, nondiabetic participants for 3 years. We measured 3 PTD markers (normoglycemic glycosuria, fractional excretion of phosphorus, and tubular proteinuria) and mGFR (by iohexol disappearance from serum) annually. We used univariate and multivariate generalized estimating equation logistic regression to identify factors associated with PTD across all visits and linear mixed effects models to assess the association between baseline PTD and mGFR slope.

Results: Compared with HIV-negative participants, HIV-positive persons that were not taking antiretroviral therapy were at increased risk of PTD (adjusted odds ratio 3.33; 95% confidence interval: 1.65 to 6.71), whereas those taking a TDF-based or a TDF-sparing regimen were not at significantly increased risk of PTD. Among HIV-positive participants, uncontrolled viremia was a strong correlate of PTD. Forty-nine of 55 (89%) participants with PTD at baseline had at least 1 subsequent visit without PTD. There was no association between baseline PTD and rate of decline in mGFR over time.

Conclusions: Poorly controlled HIV may be a stronger risk factor for PTD than TDF use. The individual-level variability of the PTD markers over time was high, potentially limiting their usefulness for routine screening in unselected patients. Baseline PTD was not associated with subsequent mGFR slope.

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*Internal Medicine Residency Training Program, Johns Hopkins Bayview Medical Center, Baltimore, MD;

Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD;

Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD;

§Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD;

Kidney Health Research Collaborative, San Francisco VA Medical Center and University of California, San Francisco, CA; and

Department of Pediatrics, University of Rochester Medical Center, Rochester, NY.

Correspondence to: Gregory M. Lucas, MD, PhD, Johns Hopkins School of Medicine, 1830 East Monument Street, Room 435A, Baltimore, MD 21287 (e-mail:

Supported by the National Institute on Drug Abuse (R01DA026770, K24DA035684). Other support was provided by the National Institute of Allergy and Infectious Diseases (T32AI102623), the National Institute of Diabetes and Digestive and Kidney Disease (U01DK082194, P01DK056492), the Johns Hopkins Institute for Clinical and Translational Research (ICTR), which is funded in part by grant number UL1-TR000424 from the National Center for Advancing Translational Sciences (NCATS), a component of the NIH, and by the Johns Hopkins Center for AIDS Research (P30AI094189). GE Healthcare provided the iohexol used for glomerular filtration rate measurements.

M.G.A. has received an institutional grant from and served as an advisor to Gilead Sciences, Inc. The remaining authors have no funding or conflicts of interest to disclose.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Received October 24, 2016

Accepted January 06, 2017

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