Back to Search Start Over

Association of Urinary Biomarkers of Kidney Injury with Estimated GFR Decline in HIV-Infected Individuals following Tenofovir Disoproxil Fumarate Initiation.

Authors :
Ascher SB
Scherzer R
Estrella MM
Zhang WR
Muiru AN
Jotwani V
Grunfeld C
Parikh CR
Gustafson D
Young M
Sharma A
Cohen MH
Ng DK
Palella FJ
Witt MD
Ho K
Shlipak MG
Source :
Clinical journal of the American Society of Nephrology : CJASN [Clin J Am Soc Nephrol] 2018 Sep 07; Vol. 13 (9), pp. 1321-1329. Date of Electronic Publication: 2018 Aug 28.
Publication Year :
2018

Abstract

Background and Objectives: Tenofovir disoproxil fumarate (tenofovir) is associated with elevated concentrations of biomarkers of kidney damage and dysfunction in individuals with HIV. The relationship of these kidney biomarkers with longitudinal kidney function decline is unknown.<br />Design, Setting, Participants, & Measurements: We evaluated associations of 14 urinary biomarkers of kidney injury with changes in eGFR among 198 men and women with HIV who initiated tenofovir between 2009 and 2015 in the Multicenter AIDS Cohort Study and Women's Interagency HIV Study. Urinary biomarkers included albumin-to-creatinine ratio, α -1-microglobulin, β -2-microglobulin, cystatin C, kidney injury molecule-1 (KIM-1), IL-18, neutrophil gelatinase-associated lipocalin (NGAL), clusterin, osteopontin, uromodulin, monocyte chemoattractant protein-1, EGF, trefoil factor 3, and chitinase 3-like protein 1. We used multivariable linear mixed-effect models controlling for demographics, traditional kidney disease risk factors, and HIV-related risk factors to evaluate associations of baseline biomarkers with first-year changes in eGFR, and associations of year 1 and first-year change in biomarkers with changes in eGFR from year 1 to year 3. We used the least absolute shrinkage and selection operator method to identify a parsimonious set of biomarkers jointly associated with changes in eGFR.<br />Results: Median eGFR before tenofovir initiation was 103 (interquartile range, 88-116) ml/min per 1.73 m <superscript>2</superscript> . During the first year of tenofovir use, eGFR decreased on average by 9.2 (95% confidence interval, 6.5 to 11.9) ml/min per 1.73 m <superscript>2</superscript> and was stable afterward (decrease of 0.62; 95% confidence interval, -0.85 to 2.1 ml/min per 1.73 m <superscript>2</superscript> per year). After multivariable adjustment, higher baseline β -2-microglobulin, KIM-1, and clusterin were associated with larger first-year eGFR declines, whereas higher baseline uromodulin was associated with a smaller eGFR decline. First-year increase in urinary cystatin C and higher year 1 IL-18 were associated with larger annual eGFR declines from year 1 to year 3. The parsimonious models identified higher pre-tenofovir clusterin and KIM-1, lower pre-tenofovir uromodulin, and higher year 1 IL-18 as jointly associated with larger eGFR declines.<br />Conclusions: Urinary biomarkers of kidney injury measured before and after tenofovir initiation are associated with subsequent changes in eGFR in individuals with HIV.<br />Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_08_28_CJASNPodcast_18_9_S.mp3.<br /> (Copyright © 2018 by the American Society of Nephrology.)

Details

Language :
English
ISSN :
1555-905X
Volume :
13
Issue :
9
Database :
MEDLINE
Journal :
Clinical journal of the American Society of Nephrology : CJASN
Publication Type :
Academic Journal
Accession number :
30154221
Full Text :
https://doi.org/10.2215/CJN.01700218