Tenofovir disoproxil fumarate initiation and changes in urinary biomarker concentrations among HIV-infected men and women
Year: 2018
Type: article
Study design: Observational Study
Abstract: OBJECTIVES: Urinary biomarkers of kidney injury may have potential to identify subclinical injury attributable to tenofovir disoproxil fumarate (TDF) toxicity. DESIGN: This observational study included 198 HIV-infected participants from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study, who initiated TDF between 2009 and 2015 and had urine samples collected at baseline before and after TDF initiation. METHODS: We used linear mixed-effects models controlling for urine creatinine and time on TDF to evaluate the effects of TDF initiation on changes in 14 urinary biomarkers. RESULTS: Within 1 year after TDF initiation, concentrations of trefoil factor 3 [+78%; 95% confidence interval (CI) +38%, +129%), alpha-1 microglobulin (α1m) (+32%; 95% CI +13%, +55%), clusterin (+21%; 95% CI +6%, +38%), uromodulin (+19%; 95% CI +4%, +36%), and kidney injury molecule-1 (KIM-1) (+13%; 95% CI +1%, +26%) significantly increased, whereas interleukin-18 (IL-18) significantly decreased (-13%, 95% CI -7%, -25%). Subsequent to the first year of TDF use, biomarker concentrations stabilized, and these changes were not statistically significant. When stratifying by baseline viremia (HIV-1 RNA < vs. ≥80 copies/ml), concentration changes for most biomarkers during the first year of TDF use were greater among aviremic vs. viremic participants, with significant differences in α1m (+80 vs. +22%), KIM-1 (+43 vs. +10%), beta-2 microglobulin (+83 vs. -10%), YKL-40 (+33 vs. -5%), and IL-18 (+20 vs. -27%). CONCLUSIONS: TDF initiation was associated with substantial changes in urinary biomarkers of kidney injury within the first year of use, particularly among aviremic participants. A urinary biomarker panel may be a clinically useful tool to detect and monitor the heterogeneous effects of TDF on the kidney.
Source: AIDS
Authors: William R. Zhang, Rebecca Scherzer, Michelle M. Estrella, Simon B. Ascher, Anthony Muiru, Vasantha Jotwani, Carl Grunfeld, Chirag R. Parikh, Deborah Gustafson, Seble Kassaye, Anjali Sharma, Mardge Cohen, Phyllis C. Tien, Derek K. Ng, Frank J. Palella, Mallory D. Witt, Ken Ho, Michael G. Shlipak
Institutions: San Francisco VA Medical Center, San Francisco VA Health Care System, University of California, Los Angeles, Johns Hopkins University, Johns Hopkins Medicine, SUNY Downstate Health Sciences University, Georgetown University Medical Center, Albert Einstein College of Medicine, Rush University, University of California, San Francisco, Northwestern University, The Lundquist Institute, Harbor–UCLA Medical Center, University of Pittsburgh
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Northwestern University, Johns Hopkins University, University of Pittsburgh, Georgia Clinical and Translational Science Alliance, National Institutes of Health, University of California, Los Angeles, University of California, San Francisco, Johns Hopkins Bloomberg School of Public Health, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, National Institute of Dental and Craniofacial Research, Office of Research on Women's Health, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Center for AIDS Research, University of North Carolina at Chapel Hill
Awards: G1089263533, G1110103167, G1111999087, G1114015694, G1166984944, G12089860, G1274611523, G1328638908, Center/Coordination, Analysis and Management/MACS, G1446261281, G1648857542, G1732606383, G1826418709, G1835874845, G196810821, G2008237588, G2072110039, G2088232294, G2127051194, G216444255, G227110230, G2277270920, G2298971178, G2334180555, G2460023850, G2583540734, G259661504, G2639424016, G2640595981, G2764864546, G2840865780, G2986904770, G3001095189, G3013054560, G3089064904, G311558797, G3130478842, G3206421427, G3219051927, G3381142117, The Connie Wofsy Women's HIV Study, G3415611610, G343705321, G3481933404, Brooklyn Women's Interagency HIV Study (WIHS) V, Miami Womens Interagency HIV Study WIHS, G3671922257, G3685536865, G3786813389, G3799046232, G3942807564, G4019075231, G403271778, Natural History of AIDS in Homosexual Men, G4166501182, G4205096527, G4230593884, G4263984760, G4333671923, G4361283536, G4371267688, WIHS Data Management and Analysis Center (WDMAC), G4500389830, G4558954805, G4584981698, G4698478974, G4763761376, G483408255, G489153995, Chicago WIHS Consortium V (CWC), G5162520385, G5411330681, G5411403494, G5502559727, Washington Women's Interagency HIV/AIDS Study, G5634615262, G5641536491, G5652173662, G5653205272, G5655542889, G5657152656, G5746236012, G5873686156, G5900455136, G592158972, G5938652292, G604406090, G6068496172, G612407757, G6270227296, G6300780520, G6341392406, G6384504179, Institute for Clinical and Translational Research, G6533371250, G6576622550, G661928818, G669420692, Multicenter AIDS Cohort Study, G6937273202, G6944561475, G6990385686, G7000745727, University of North Carolina Womens Interagency HIV Study UNC WIHS, G7140729675, G7479905529, G7512160369, G767062161, G773494495, G775892330, G7807729167, G8039576609, G8327600025, G8448522485, G8846374971, UAB-MISS WIHS Cohort, G9000009364, G9000021013, G9000029981, G9000030772, G9000031392, G9000039899, G9000052758, G9000059706, G9000070603, G9000080293, G9000081039, G9000082816, G9000084207, G9000110076, G9000122276, G9000177630, G9000204903, G9000216739, Biomarker-Based Diagnostic Algorithms To Prevent, Detect And Guide Treatment Of Kidney Disease In Persons Living With HIV, NRSA Training Core, The University of North Carolina Center for AIDS Research, Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS) - Baltimore/Wash DC Center, UCLA Clinical and Translational Science Institute, G901243891, G97119092, G986692823
OpenAlex ID: W2906253699