Urinary biomarkers of kidney injury are associated with all-cause mortality in the Women's Interagency HIV Study (WIHS)

C. A. Peralta, R. Scherzer, C. Grunfeld, A. Abraham, P. C. Tien, P. Devarajan, M. Bennett, A. W. Butch, Kathryn Anastos, M. H. Cohen, M. Nowicki, Anjali Sharma, M. A. Young, M. J. Sarnak, C. R. Parikh, M. G. Shlipak

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Objectives: Chronic kidney disease (CKD) is common in HIV-infected individuals, and is associated with mortality in both the HIV-infected and general populations. Urinary markers of tubular injury have been associated with future kidney disease risk, but associations with mortality are unknown. Methods: We evaluated the associations of urinary interleukin-18 (IL-18), liver fatty acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and the albumin-to-creatinine ratio (ACR) with 10-year, all-cause death in 908 HIV-infected women. Serum cystatin C was used to estimate the glomerular filtration rate (eGFRcys). Results: There were 201 deaths during 9269 person-years of follow-up. After demographic adjustment, compared with the lowest tertile, the highest tertiles of IL-18 [hazard ratio (HR) 2.54; 95% confidence interval (CI) 1.75-3.68], KIM-1 (HR 2.04; 95% CI 1.44-2.89), NGAL (HR 1.50; 95% CI 1.05-2.14) and ACR (HR 1.63; 95% CI 1.13-2.36) were associated with higher mortality. After multivariable adjustment including adjustment for eGFRcys, only the highest tertiles of IL-18 (HR 1.88; 95% CI 1.29-2.74) and ACR (HR 1.46; 95% CI 1.01-2.12) remained independently associated with mortality. Findings for KIM-1 were borderline (HR 1.41; 95% CI 0.99-2.02). We found a J-shaped association between L-FABP and mortality. Compared with persons in the lowest tertile, the HR for the middle tertile of L-FABP was 0.67 (95% CI 0.46-0.98) after adjustment. Associations were stronger when IL-18, ACR and L-FABP were simultaneously included in models. Conclusions: Among HIV-infected women, some urinary markers of tubular injury are associated with mortality risk, independently of eGFRcys and ACR. These markers represent potential tools with which to identify early kidney injury in persons with HIV infection.

Original languageEnglish (US)
Pages (from-to)291-300
Number of pages10
JournalHIV Medicine
Volume15
Issue number5
DOIs
StatePublished - 2014

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Biomarkers
HIV
Confidence Intervals
Kidney
Fatty Acid-Binding Proteins
Interleukin-18
Mortality
Wounds and Injuries
Albumins
Creatinine
Cystatin C
Kidney Diseases
Glomerular Filtration Rate
Chronic Renal Insufficiency
HIV Infections
Cause of Death
Demography
Serum
Population

Keywords

  • HIV
  • Interleukin-18
  • Kidney injury molecule-1
  • Liver fatty acid binding protein
  • Neutrophil gelatinase-associated lipocalin
  • Urinary biomarkers

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Health Policy

Cite this

Peralta, C. A., Scherzer, R., Grunfeld, C., Abraham, A., Tien, P. C., Devarajan, P., ... Shlipak, M. G. (2014). Urinary biomarkers of kidney injury are associated with all-cause mortality in the Women's Interagency HIV Study (WIHS). HIV Medicine, 15(5), 291-300. https://doi.org/10.1111/hiv.12113

Urinary biomarkers of kidney injury are associated with all-cause mortality in the Women's Interagency HIV Study (WIHS). / Peralta, C. A.; Scherzer, R.; Grunfeld, C.; Abraham, A.; Tien, P. C.; Devarajan, P.; Bennett, M.; Butch, A. W.; Anastos, Kathryn; Cohen, M. H.; Nowicki, M.; Sharma, Anjali; Young, M. A.; Sarnak, M. J.; Parikh, C. R.; Shlipak, M. G.

In: HIV Medicine, Vol. 15, No. 5, 2014, p. 291-300.

Research output: Contribution to journalArticle

Peralta, CA, Scherzer, R, Grunfeld, C, Abraham, A, Tien, PC, Devarajan, P, Bennett, M, Butch, AW, Anastos, K, Cohen, MH, Nowicki, M, Sharma, A, Young, MA, Sarnak, MJ, Parikh, CR & Shlipak, MG 2014, 'Urinary biomarkers of kidney injury are associated with all-cause mortality in the Women's Interagency HIV Study (WIHS)', HIV Medicine, vol. 15, no. 5, pp. 291-300. https://doi.org/10.1111/hiv.12113
Peralta, C. A. ; Scherzer, R. ; Grunfeld, C. ; Abraham, A. ; Tien, P. C. ; Devarajan, P. ; Bennett, M. ; Butch, A. W. ; Anastos, Kathryn ; Cohen, M. H. ; Nowicki, M. ; Sharma, Anjali ; Young, M. A. ; Sarnak, M. J. ; Parikh, C. R. ; Shlipak, M. G. / Urinary biomarkers of kidney injury are associated with all-cause mortality in the Women's Interagency HIV Study (WIHS). In: HIV Medicine. 2014 ; Vol. 15, No. 5. pp. 291-300.
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abstract = "Objectives: Chronic kidney disease (CKD) is common in HIV-infected individuals, and is associated with mortality in both the HIV-infected and general populations. Urinary markers of tubular injury have been associated with future kidney disease risk, but associations with mortality are unknown. Methods: We evaluated the associations of urinary interleukin-18 (IL-18), liver fatty acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and the albumin-to-creatinine ratio (ACR) with 10-year, all-cause death in 908 HIV-infected women. Serum cystatin C was used to estimate the glomerular filtration rate (eGFRcys). Results: There were 201 deaths during 9269 person-years of follow-up. After demographic adjustment, compared with the lowest tertile, the highest tertiles of IL-18 [hazard ratio (HR) 2.54; 95{\%} confidence interval (CI) 1.75-3.68], KIM-1 (HR 2.04; 95{\%} CI 1.44-2.89), NGAL (HR 1.50; 95{\%} CI 1.05-2.14) and ACR (HR 1.63; 95{\%} CI 1.13-2.36) were associated with higher mortality. After multivariable adjustment including adjustment for eGFRcys, only the highest tertiles of IL-18 (HR 1.88; 95{\%} CI 1.29-2.74) and ACR (HR 1.46; 95{\%} CI 1.01-2.12) remained independently associated with mortality. Findings for KIM-1 were borderline (HR 1.41; 95{\%} CI 0.99-2.02). We found a J-shaped association between L-FABP and mortality. Compared with persons in the lowest tertile, the HR for the middle tertile of L-FABP was 0.67 (95{\%} CI 0.46-0.98) after adjustment. Associations were stronger when IL-18, ACR and L-FABP were simultaneously included in models. Conclusions: Among HIV-infected women, some urinary markers of tubular injury are associated with mortality risk, independently of eGFRcys and ACR. These markers represent potential tools with which to identify early kidney injury in persons with HIV infection.",
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author = "Peralta, {C. A.} and R. Scherzer and C. Grunfeld and A. Abraham and Tien, {P. C.} and P. Devarajan and M. Bennett and Butch, {A. W.} and Kathryn Anastos and Cohen, {M. H.} and M. Nowicki and Anjali Sharma and Young, {M. A.} and Sarnak, {M. J.} and Parikh, {C. R.} and Shlipak, {M. G.}",
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TY - JOUR

T1 - Urinary biomarkers of kidney injury are associated with all-cause mortality in the Women's Interagency HIV Study (WIHS)

AU - Peralta, C. A.

AU - Scherzer, R.

AU - Grunfeld, C.

AU - Abraham, A.

AU - Tien, P. C.

AU - Devarajan, P.

AU - Bennett, M.

AU - Butch, A. W.

AU - Anastos, Kathryn

AU - Cohen, M. H.

AU - Nowicki, M.

AU - Sharma, Anjali

AU - Young, M. A.

AU - Sarnak, M. J.

AU - Parikh, C. R.

AU - Shlipak, M. G.

PY - 2014

Y1 - 2014

N2 - Objectives: Chronic kidney disease (CKD) is common in HIV-infected individuals, and is associated with mortality in both the HIV-infected and general populations. Urinary markers of tubular injury have been associated with future kidney disease risk, but associations with mortality are unknown. Methods: We evaluated the associations of urinary interleukin-18 (IL-18), liver fatty acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and the albumin-to-creatinine ratio (ACR) with 10-year, all-cause death in 908 HIV-infected women. Serum cystatin C was used to estimate the glomerular filtration rate (eGFRcys). Results: There were 201 deaths during 9269 person-years of follow-up. After demographic adjustment, compared with the lowest tertile, the highest tertiles of IL-18 [hazard ratio (HR) 2.54; 95% confidence interval (CI) 1.75-3.68], KIM-1 (HR 2.04; 95% CI 1.44-2.89), NGAL (HR 1.50; 95% CI 1.05-2.14) and ACR (HR 1.63; 95% CI 1.13-2.36) were associated with higher mortality. After multivariable adjustment including adjustment for eGFRcys, only the highest tertiles of IL-18 (HR 1.88; 95% CI 1.29-2.74) and ACR (HR 1.46; 95% CI 1.01-2.12) remained independently associated with mortality. Findings for KIM-1 were borderline (HR 1.41; 95% CI 0.99-2.02). We found a J-shaped association between L-FABP and mortality. Compared with persons in the lowest tertile, the HR for the middle tertile of L-FABP was 0.67 (95% CI 0.46-0.98) after adjustment. Associations were stronger when IL-18, ACR and L-FABP were simultaneously included in models. Conclusions: Among HIV-infected women, some urinary markers of tubular injury are associated with mortality risk, independently of eGFRcys and ACR. These markers represent potential tools with which to identify early kidney injury in persons with HIV infection.

AB - Objectives: Chronic kidney disease (CKD) is common in HIV-infected individuals, and is associated with mortality in both the HIV-infected and general populations. Urinary markers of tubular injury have been associated with future kidney disease risk, but associations with mortality are unknown. Methods: We evaluated the associations of urinary interleukin-18 (IL-18), liver fatty acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and the albumin-to-creatinine ratio (ACR) with 10-year, all-cause death in 908 HIV-infected women. Serum cystatin C was used to estimate the glomerular filtration rate (eGFRcys). Results: There were 201 deaths during 9269 person-years of follow-up. After demographic adjustment, compared with the lowest tertile, the highest tertiles of IL-18 [hazard ratio (HR) 2.54; 95% confidence interval (CI) 1.75-3.68], KIM-1 (HR 2.04; 95% CI 1.44-2.89), NGAL (HR 1.50; 95% CI 1.05-2.14) and ACR (HR 1.63; 95% CI 1.13-2.36) were associated with higher mortality. After multivariable adjustment including adjustment for eGFRcys, only the highest tertiles of IL-18 (HR 1.88; 95% CI 1.29-2.74) and ACR (HR 1.46; 95% CI 1.01-2.12) remained independently associated with mortality. Findings for KIM-1 were borderline (HR 1.41; 95% CI 0.99-2.02). We found a J-shaped association between L-FABP and mortality. Compared with persons in the lowest tertile, the HR for the middle tertile of L-FABP was 0.67 (95% CI 0.46-0.98) after adjustment. Associations were stronger when IL-18, ACR and L-FABP were simultaneously included in models. Conclusions: Among HIV-infected women, some urinary markers of tubular injury are associated with mortality risk, independently of eGFRcys and ACR. These markers represent potential tools with which to identify early kidney injury in persons with HIV infection.

KW - HIV

KW - Interleukin-18

KW - Kidney injury molecule-1

KW - Liver fatty acid binding protein

KW - Neutrophil gelatinase-associated lipocalin

KW - Urinary biomarkers

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