Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans

Vishal S. Vaidya, Sushrut S. Waikar, Michael A. Ferguson, Fitz B. Collings, Kelsey Sunderland, Costas Gioules, Gary Bradwin, Roland Matsouaka, Rebecca Betensky, Gary C. Curhan, Joseph V. Bonventre

Research output: Contribution to journalArticle

Abstract

Acute kidney injury (AKI) is associated with high morbidity and mortality. The lack of sensitive and specific injury biomarkers has greatly impeded the development of therapeutic strategies to improve outcomes of AKI. The unique objective of this study was to evaluate the diagnostic performance of nine urinary biomarkers of AKI-kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), interleukin-18 (IL-18), hepatocyte growth factor (HGF), cystatin C (Cys), N-acetyl-β-D-glucosaminidase (NAG), vascular endothelial growth factor (VEGF), chemokine interferon-inducible protein 10 (IP-10; CXCL10), and total protein-in a cross-sectional comparison of 204 patients with or without AKI. Median urinary concentrations of each biomarker were significantly higher in patients with AKI than in those without AKI (p < 0.001). The area under the receiver operating characteristics curve (AUC-ROC) for the combination of biomarkers using a logic regression model [risk score of 2.93*(NGAL > 5.72 and HGF > 0.17) + 2.93*(PROTEIN > 0.22) -2*(KIM < 0.58)] was greater (0.94) than individual biomarker AUC-ROCs. Age-adjusted levels of urinary KIM-1, NAG, HGF, VEGF, and total protein were significantly higher in patients who died or required renal replacement therapy (RRT) when compared to those who survived and did not require RRT. Our results demonstrate the comparative value of multiple biomarkers in the diagnosis and prognosis of AKI.

Original languageEnglish (US)
Pages (from-to)200-208
Number of pages9
JournalClinical and Translational Science
Volume1
Issue number3
DOIs
StatePublished - Dec 1 2008

Fingerprint

Biomarkers
Acute Kidney Injury
Hepatocyte Growth Factor
Hexosaminidases
Vascular Endothelial Growth Factor A
Renal Replacement Therapy
Chemokine CXCL10
Lipocalins
Cystatin C
Gelatinases
Interleukin-18
Molecules
Wounds and Injuries
Vascular Endothelial Growth Factor D
Chemokines
Kidney
Proteins
Area Under Curve
Morbidity
Mortality

Keywords

  • Acute kidney injury
  • Biomarkers
  • Hepatocyte growth factor
  • Kidney injury molecule-1
  • Neutrophil gelatinase associated lipocalin

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Vaidya, V. S., Waikar, S. S., Ferguson, M. A., Collings, F. B., Sunderland, K., Gioules, C., ... Bonventre, J. V. (2008). Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clinical and Translational Science, 1(3), 200-208. https://doi.org/10.1111/j.1752-8062.2008.00053.x

Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. / Vaidya, Vishal S.; Waikar, Sushrut S.; Ferguson, Michael A.; Collings, Fitz B.; Sunderland, Kelsey; Gioules, Costas; Bradwin, Gary; Matsouaka, Roland; Betensky, Rebecca; Curhan, Gary C.; Bonventre, Joseph V.

In: Clinical and Translational Science, Vol. 1, No. 3, 01.12.2008, p. 200-208.

Research output: Contribution to journalArticle

Vaidya, VS, Waikar, SS, Ferguson, MA, Collings, FB, Sunderland, K, Gioules, C, Bradwin, G, Matsouaka, R, Betensky, R, Curhan, GC & Bonventre, JV 2008, 'Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans', Clinical and Translational Science, vol. 1, no. 3, pp. 200-208. https://doi.org/10.1111/j.1752-8062.2008.00053.x
Vaidya, Vishal S. ; Waikar, Sushrut S. ; Ferguson, Michael A. ; Collings, Fitz B. ; Sunderland, Kelsey ; Gioules, Costas ; Bradwin, Gary ; Matsouaka, Roland ; Betensky, Rebecca ; Curhan, Gary C. ; Bonventre, Joseph V. / Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. In: Clinical and Translational Science. 2008 ; Vol. 1, No. 3. pp. 200-208.
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AB - Acute kidney injury (AKI) is associated with high morbidity and mortality. The lack of sensitive and specific injury biomarkers has greatly impeded the development of therapeutic strategies to improve outcomes of AKI. The unique objective of this study was to evaluate the diagnostic performance of nine urinary biomarkers of AKI-kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), interleukin-18 (IL-18), hepatocyte growth factor (HGF), cystatin C (Cys), N-acetyl-β-D-glucosaminidase (NAG), vascular endothelial growth factor (VEGF), chemokine interferon-inducible protein 10 (IP-10; CXCL10), and total protein-in a cross-sectional comparison of 204 patients with or without AKI. Median urinary concentrations of each biomarker were significantly higher in patients with AKI than in those without AKI (p < 0.001). The area under the receiver operating characteristics curve (AUC-ROC) for the combination of biomarkers using a logic regression model [risk score of 2.93*(NGAL > 5.72 and HGF > 0.17) + 2.93*(PROTEIN > 0.22) -2*(KIM < 0.58)] was greater (0.94) than individual biomarker AUC-ROCs. Age-adjusted levels of urinary KIM-1, NAG, HGF, VEGF, and total protein were significantly higher in patients who died or required renal replacement therapy (RRT) when compared to those who survived and did not require RRT. Our results demonstrate the comparative value of multiple biomarkers in the diagnosis and prognosis of AKI.

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