Tenofovir use and urinary biomarkers among HIV-infected women in the women's interagency HIV study (WIHS)

Ikwo Oboho, Alison G. Abraham, Lorie Benning, Kathryn Anastos, Anjali Sharma, Mary Young, Pamela Burian, Monica Gandhi, Mardge Cohen, Lynda Szczech

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Tenofovir (TDF) has been associated with renal tubular injury. Biomarkers that signal early tubular dysfunction are needed because creatinine rise lags behind TDF-associated kidney dysfunction. We examined several urinary biomarkers to determine if rises accompanying TDF initiation preceded creatinine changes. Methods: Three urinary biomarkers of tubular impairment-neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-b-D-glucosaminidase (NAG), and b-2-microglobulin (b2MG)-were measured across 3 time points (one pre-TDF visit and 2 post-TDF visits) in 132 HIV-positive women from the Women's Interagency HIV Study. Women initiating highly active antiretroviral therapy (HAART) containing TDF were propensity score matched to women initiating HAART without TDF and women not on HAART. Results: There were no differences between groups for NGAL or NAG, but b2MG was 19 times more likely to be elevated among TDF users at the second post-TDF visit compared with non-TDF users at the pre-TDF visit (P , 0.01). History of proteinuria was associated with elevated NGAL (P , 0.01). Factors associated with elevated NAG were glomerular filtration rate ,60 mL/minute, history of proteinuria, hepatitis C (P , 0.01 for all), and diabetes mellitus (P = 0.05). Factors associated with increased odds of elevated b2MG were HIV RNA .100,000 copies/mL, hepatitis C, boosted protease inhibitor use, and glomerular filtration rate ,60 mL/minute (P # 0.01 for all). Conclusions: b2MG levels are elevated in women on TDF, indicating probable early renal dysfunction. Biomarker elevation is additionally associated with baseline chronic kidney disease, uncontrolled viremia, and boosted protease inhibitor use. Future studies are needed to explore urinary biomarker thresholds in identifying treated HIVinfected individuals at risk for renal dysfunction.

Original languageEnglish (US)
Pages (from-to)388-395
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume62
Issue number4
DOIs
StatePublished - Apr 1 2013

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Tenofovir
Biomarkers
HIV
Hexosaminidases
Highly Active Antiretroviral Therapy
Kidney
Hepatitis C
Protease Inhibitors
Glomerular Filtration Rate
Proteinuria
Creatinine
Propensity Score
Viremia
Chronic Renal Insufficiency
Diabetes Mellitus

Keywords

  • HIV-infected women
  • Tenofovir
  • Urinary biomarkers

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Tenofovir use and urinary biomarkers among HIV-infected women in the women's interagency HIV study (WIHS). / Oboho, Ikwo; Abraham, Alison G.; Benning, Lorie; Anastos, Kathryn; Sharma, Anjali; Young, Mary; Burian, Pamela; Gandhi, Monica; Cohen, Mardge; Szczech, Lynda.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 62, No. 4, 01.04.2013, p. 388-395.

Research output: Contribution to journalArticle

Oboho, Ikwo ; Abraham, Alison G. ; Benning, Lorie ; Anastos, Kathryn ; Sharma, Anjali ; Young, Mary ; Burian, Pamela ; Gandhi, Monica ; Cohen, Mardge ; Szczech, Lynda. / Tenofovir use and urinary biomarkers among HIV-infected women in the women's interagency HIV study (WIHS). In: Journal of Acquired Immune Deficiency Syndromes. 2013 ; Vol. 62, No. 4. pp. 388-395.
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abstract = "Background: Tenofovir (TDF) has been associated with renal tubular injury. Biomarkers that signal early tubular dysfunction are needed because creatinine rise lags behind TDF-associated kidney dysfunction. We examined several urinary biomarkers to determine if rises accompanying TDF initiation preceded creatinine changes. Methods: Three urinary biomarkers of tubular impairment-neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-b-D-glucosaminidase (NAG), and b-2-microglobulin (b2MG)-were measured across 3 time points (one pre-TDF visit and 2 post-TDF visits) in 132 HIV-positive women from the Women's Interagency HIV Study. Women initiating highly active antiretroviral therapy (HAART) containing TDF were propensity score matched to women initiating HAART without TDF and women not on HAART. Results: There were no differences between groups for NGAL or NAG, but b2MG was 19 times more likely to be elevated among TDF users at the second post-TDF visit compared with non-TDF users at the pre-TDF visit (P , 0.01). History of proteinuria was associated with elevated NGAL (P , 0.01). Factors associated with elevated NAG were glomerular filtration rate ,60 mL/minute, history of proteinuria, hepatitis C (P , 0.01 for all), and diabetes mellitus (P = 0.05). Factors associated with increased odds of elevated b2MG were HIV RNA .100,000 copies/mL, hepatitis C, boosted protease inhibitor use, and glomerular filtration rate ,60 mL/minute (P # 0.01 for all). Conclusions: b2MG levels are elevated in women on TDF, indicating probable early renal dysfunction. Biomarker elevation is additionally associated with baseline chronic kidney disease, uncontrolled viremia, and boosted protease inhibitor use. Future studies are needed to explore urinary biomarker thresholds in identifying treated HIVinfected individuals at risk for renal dysfunction.",
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T1 - Tenofovir use and urinary biomarkers among HIV-infected women in the women's interagency HIV study (WIHS)

AU - Oboho, Ikwo

AU - Abraham, Alison G.

AU - Benning, Lorie

AU - Anastos, Kathryn

AU - Sharma, Anjali

AU - Young, Mary

AU - Burian, Pamela

AU - Gandhi, Monica

AU - Cohen, Mardge

AU - Szczech, Lynda

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N2 - Background: Tenofovir (TDF) has been associated with renal tubular injury. Biomarkers that signal early tubular dysfunction are needed because creatinine rise lags behind TDF-associated kidney dysfunction. We examined several urinary biomarkers to determine if rises accompanying TDF initiation preceded creatinine changes. Methods: Three urinary biomarkers of tubular impairment-neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-b-D-glucosaminidase (NAG), and b-2-microglobulin (b2MG)-were measured across 3 time points (one pre-TDF visit and 2 post-TDF visits) in 132 HIV-positive women from the Women's Interagency HIV Study. Women initiating highly active antiretroviral therapy (HAART) containing TDF were propensity score matched to women initiating HAART without TDF and women not on HAART. Results: There were no differences between groups for NGAL or NAG, but b2MG was 19 times more likely to be elevated among TDF users at the second post-TDF visit compared with non-TDF users at the pre-TDF visit (P , 0.01). History of proteinuria was associated with elevated NGAL (P , 0.01). Factors associated with elevated NAG were glomerular filtration rate ,60 mL/minute, history of proteinuria, hepatitis C (P , 0.01 for all), and diabetes mellitus (P = 0.05). Factors associated with increased odds of elevated b2MG were HIV RNA .100,000 copies/mL, hepatitis C, boosted protease inhibitor use, and glomerular filtration rate ,60 mL/minute (P # 0.01 for all). Conclusions: b2MG levels are elevated in women on TDF, indicating probable early renal dysfunction. Biomarker elevation is additionally associated with baseline chronic kidney disease, uncontrolled viremia, and boosted protease inhibitor use. Future studies are needed to explore urinary biomarker thresholds in identifying treated HIVinfected individuals at risk for renal dysfunction.

AB - Background: Tenofovir (TDF) has been associated with renal tubular injury. Biomarkers that signal early tubular dysfunction are needed because creatinine rise lags behind TDF-associated kidney dysfunction. We examined several urinary biomarkers to determine if rises accompanying TDF initiation preceded creatinine changes. Methods: Three urinary biomarkers of tubular impairment-neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-b-D-glucosaminidase (NAG), and b-2-microglobulin (b2MG)-were measured across 3 time points (one pre-TDF visit and 2 post-TDF visits) in 132 HIV-positive women from the Women's Interagency HIV Study. Women initiating highly active antiretroviral therapy (HAART) containing TDF were propensity score matched to women initiating HAART without TDF and women not on HAART. Results: There were no differences between groups for NGAL or NAG, but b2MG was 19 times more likely to be elevated among TDF users at the second post-TDF visit compared with non-TDF users at the pre-TDF visit (P , 0.01). History of proteinuria was associated with elevated NGAL (P , 0.01). Factors associated with elevated NAG were glomerular filtration rate ,60 mL/minute, history of proteinuria, hepatitis C (P , 0.01 for all), and diabetes mellitus (P = 0.05). Factors associated with increased odds of elevated b2MG were HIV RNA .100,000 copies/mL, hepatitis C, boosted protease inhibitor use, and glomerular filtration rate ,60 mL/minute (P # 0.01 for all). Conclusions: b2MG levels are elevated in women on TDF, indicating probable early renal dysfunction. Biomarker elevation is additionally associated with baseline chronic kidney disease, uncontrolled viremia, and boosted protease inhibitor use. Future studies are needed to explore urinary biomarker thresholds in identifying treated HIVinfected individuals at risk for renal dysfunction.

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KW - Urinary biomarkers

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