Tenofovir disoproxil fumarate initiation and changes in urinary biomarker concentrations among HIV-infected men and women

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)723-733
Number of pages11
JournalAIDS (London, England)
Volume33
Issue number4
DOIs
StatePublished - Mar 15 2019

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Tenofovir
Biomarkers
HIV
Confidence Intervals
Kidney
Wounds and Injuries
Interleukin-18
Uromodulin
Urine
Clusterin
beta 2-Microglobulin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Zhang, W. R., Scherzer, R., Estrella, M. M., Ascher, S. B., Muiru, A., Jotwani, V., ... Shlipak, M. G. (2019). Tenofovir disoproxil fumarate initiation and changes in urinary biomarker concentrations among HIV-infected men and women. AIDS (London, England), 33(4), 723-733. https://doi.org/10.1097/QAD.0000000000002114

Tenofovir disoproxil fumarate initiation and changes in urinary biomarker concentrations among HIV-infected men and women. / Zhang, William R.; Scherzer, Rebecca; Estrella, Michelle M.; Ascher, Simon B.; Muiru, Anthony; Jotwani, Vasantha; Grunfeld, Carl; Parikh, Chirag R.; Gustafson, Deborah; Kassaye, Seble; Sharma, Anjali; Cohen, Mardge; Tien, Phyllis C.; Ng, Derek K.; Palella, Frank J.; Witt, Mallory D.; Ho, Ken; Shlipak, Michael G.

In: AIDS (London, England), Vol. 33, No. 4, 15.03.2019, p. 723-733.

Research output: Contribution to journalArticle

Zhang, WR, Scherzer, R, Estrella, MM, Ascher, SB, Muiru, A, Jotwani, V, Grunfeld, C, Parikh, CR, Gustafson, D, Kassaye, S, Sharma, A, Cohen, M, Tien, PC, Ng, DK, Palella, FJ, Witt, MD, Ho, K & Shlipak, MG 2019, 'Tenofovir disoproxil fumarate initiation and changes in urinary biomarker concentrations among HIV-infected men and women', AIDS (London, England), vol. 33, no. 4, pp. 723-733. https://doi.org/10.1097/QAD.0000000000002114
Zhang, William R. ; Scherzer, Rebecca ; Estrella, Michelle M. ; Ascher, Simon B. ; Muiru, Anthony ; Jotwani, Vasantha ; Grunfeld, Carl ; Parikh, Chirag R. ; Gustafson, Deborah ; Kassaye, Seble ; Sharma, Anjali ; Cohen, Mardge ; Tien, Phyllis C. ; Ng, Derek K. ; Palella, Frank J. ; Witt, Mallory D. ; Ho, Ken ; Shlipak, Michael G. / Tenofovir disoproxil fumarate initiation and changes in urinary biomarker concentrations among HIV-infected men and women. In: AIDS (London, England). 2019 ; Vol. 33, No. 4. pp. 723-733.
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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.",
author = "Zhang, {William R.} and Rebecca Scherzer and Estrella, {Michelle M.} and Ascher, {Simon B.} and Anthony Muiru and Vasantha Jotwani and Carl Grunfeld and Parikh, {Chirag R.} and Deborah Gustafson and Seble Kassaye and Anjali Sharma and Mardge Cohen and Tien, {Phyllis C.} and Ng, {Derek K.} and Palella, {Frank J.} and Witt, {Mallory D.} and Ken Ho and Shlipak, {Michael G.}",
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T1 - Tenofovir disoproxil fumarate initiation and changes in urinary biomarker concentrations among HIV-infected men and women

AU - Zhang, William R.

AU - Scherzer, Rebecca

AU - Estrella, Michelle M.

AU - Ascher, Simon B.

AU - Muiru, Anthony

AU - Jotwani, Vasantha

AU - Grunfeld, Carl

AU - Parikh, Chirag R.

AU - Gustafson, Deborah

AU - Kassaye, Seble

AU - Sharma, Anjali

AU - Cohen, Mardge

AU - Tien, Phyllis C.

AU - Ng, Derek K.

AU - Palella, Frank J.

AU - Witt, Mallory D.

AU - Ho, Ken

AU - Shlipak, Michael G.

PY - 2019/3/15

Y1 - 2019/3/15

N2 - 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.

AB - 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.

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