Association of urinary biomarkers of kidney injury with estimated GFR decline in HIV-infected individuals following tenofovir disoproxil fumarate initiation

Simon B. Ascher, Rebecca Scherzer, Michelle M. Estrella, William R. Zhang, Anthony N. Muiru, Vasantha Jotwani, Carl Grunfeld, Chirag Parikh, Deborah Gustafson, Mary Young, Anjali Sharma, Mardge H. Cohen, Derek Ng, Frank J. Palella, Mallory D. Witt, Ken Ho, Michael G. Shlipak

Research output: Contribution to journalArticle

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. 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. Results Median eGFR before tenofovir initiation was 103 (interquartile range, 88–116) ml/min per 1.73 m2. 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 m2 and was stable afterward (decrease of 0.62; 95% confidence interval,-0.85 to 2.1 ml/min per 1.73 m2 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. Conclusions Urinary biomarkers of kidney injury measured before and after tenofovir initiation are associated with subsequent changes in eGFR in individuals with HIV.

Original languageEnglish (US)
Pages (from-to)1321-1329
Number of pages9
JournalClinical Journal of the American Society of Nephrology
Volume13
Issue number9
DOIs
StatePublished - Sep 7 2018

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Tenofovir
Biomarkers
HIV
Kidney
Wounds and Injuries
Uromodulin
Clusterin
Interleukin-18
Cystatin C
Confidence Intervals
Lipocalins
Osteopontin
Chemokine CCL2
Kidney Diseases
Epidermal Growth Factor

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

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Association of urinary biomarkers of kidney injury with estimated GFR decline in HIV-infected individuals following tenofovir disoproxil fumarate initiation. / Ascher, Simon B.; Scherzer, Rebecca; Estrella, Michelle M.; Zhang, William R.; Muiru, Anthony N.; Jotwani, Vasantha; Grunfeld, Carl; Parikh, Chirag; Gustafson, Deborah; Young, Mary; Sharma, Anjali; Cohen, Mardge H.; Ng, Derek; Palella, Frank J.; Witt, Mallory D.; Ho, Ken; Shlipak, Michael G.

In: Clinical Journal of the American Society of Nephrology, Vol. 13, No. 9, 07.09.2018, p. 1321-1329.

Research output: Contribution to journalArticle

Ascher, SB, Scherzer, R, Estrella, MM, Zhang, WR, Muiru, AN, Jotwani, V, Grunfeld, C, Parikh, C, Gustafson, D, Young, M, Sharma, A, Cohen, MH, Ng, D, Palella, FJ, Witt, MD, Ho, K & Shlipak, MG 2018, 'Association of urinary biomarkers of kidney injury with estimated GFR decline in HIV-infected individuals following tenofovir disoproxil fumarate initiation', Clinical Journal of the American Society of Nephrology, vol. 13, no. 9, pp. 1321-1329. https://doi.org/10.2215/CJN.01700218
Ascher, Simon B. ; Scherzer, Rebecca ; Estrella, Michelle M. ; Zhang, William R. ; Muiru, Anthony N. ; Jotwani, Vasantha ; Grunfeld, Carl ; Parikh, Chirag ; Gustafson, Deborah ; Young, Mary ; Sharma, Anjali ; Cohen, Mardge H. ; Ng, Derek ; Palella, Frank J. ; Witt, Mallory D. ; Ho, Ken ; Shlipak, Michael G. / Association of urinary biomarkers of kidney injury with estimated GFR decline in HIV-infected individuals following tenofovir disoproxil fumarate initiation. In: Clinical Journal of the American Society of Nephrology. 2018 ; Vol. 13, No. 9. pp. 1321-1329.
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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. 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. Results Median eGFR before tenofovir initiation was 103 (interquartile range, 88–116) ml/min per 1.73 m2. 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 m2 and was stable afterward (decrease of 0.62; 95{\%} confidence interval,-0.85 to 2.1 ml/min per 1.73 m2 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. Conclusions Urinary biomarkers of kidney injury measured before and after tenofovir initiation are associated with subsequent changes in eGFR in individuals with HIV.",
author = "Ascher, {Simon B.} and Rebecca Scherzer and Estrella, {Michelle M.} and Zhang, {William R.} and Muiru, {Anthony N.} and Vasantha Jotwani and Carl Grunfeld and Chirag Parikh and Deborah Gustafson and Mary Young and Anjali Sharma and Cohen, {Mardge H.} and Derek Ng and Palella, {Frank J.} and Witt, {Mallory D.} and Ken Ho and Shlipak, {Michael G.}",
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T1 - Association of urinary biomarkers of kidney injury with estimated GFR decline in HIV-infected individuals following tenofovir disoproxil fumarate initiation

AU - Ascher, Simon B.

AU - Scherzer, Rebecca

AU - Estrella, Michelle M.

AU - Zhang, William R.

AU - Muiru, Anthony N.

AU - Jotwani, Vasantha

AU - Grunfeld, Carl

AU - Parikh, Chirag

AU - Gustafson, Deborah

AU - Young, Mary

AU - Sharma, Anjali

AU - Cohen, Mardge H.

AU - Ng, Derek

AU - Palella, Frank J.

AU - Witt, Mallory D.

AU - Ho, Ken

AU - Shlipak, Michael G.

PY - 2018/9/7

Y1 - 2018/9/7

N2 - 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. 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. Results Median eGFR before tenofovir initiation was 103 (interquartile range, 88–116) ml/min per 1.73 m2. 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 m2 and was stable afterward (decrease of 0.62; 95% confidence interval,-0.85 to 2.1 ml/min per 1.73 m2 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. Conclusions Urinary biomarkers of kidney injury measured before and after tenofovir initiation are associated with subsequent changes in eGFR in individuals with HIV.

AB - 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. 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. Results Median eGFR before tenofovir initiation was 103 (interquartile range, 88–116) ml/min per 1.73 m2. 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 m2 and was stable afterward (decrease of 0.62; 95% confidence interval,-0.85 to 2.1 ml/min per 1.73 m2 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. Conclusions Urinary biomarkers of kidney injury measured before and after tenofovir initiation are associated with subsequent changes in eGFR in individuals with HIV.

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