Fibrinogen excretion in the urine and immunoreactivity in the kidney serves as a translational biomarker for acute kidney injury

Am J Pathol. 2012 Sep;181(3):818-28. doi: 10.1016/j.ajpath.2012.06.004. Epub 2012 Jul 20.

Abstract

Fibrinogen (Fg) is significantly up-regulated in the kidney after acute kidney injury (AKI). We evaluated the performance of Fg as a biomarker for early detection of AKI. In rats and mice with kidney tubular damage induced by ischemia/reperfusion (I/R) or cisplatin administration, respectively; kidney tissue and urinary Fg increased significantly and correlated with histopathological injury, urinary kidney injury molecule-1 (KIM-1) and N-acetyl glucosaminidase (NAG) corresponding to the progression and regression of injury temporally. In a longitudinal follow-up of 31 patients who underwent surgical repair of abdominal aortic aneurysm, urinary Fg increased earlier than SCr in patients who developed postoperative AKI (AUC-ROC = 0.72). Furthermore, in a cohort of patients with biopsy-proven AKI (n = 53), Fg immunoreactivity in the tubules and interstitium increased remarkably and was able to distinguish patients with AKI from those without AKI (n = 59). These results suggest that immunoreactivity of Fg in the kidney, as well as urinary excretion of Fg, serves as a sensitive and early diagnostic translational biomarker for detection of AKI.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury / complications
  • Acute Kidney Injury / diagnosis*
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / urine*
  • Aged
  • Animals
  • Aortic Aneurysm, Abdominal / surgery
  • Aortic Aneurysm, Abdominal / urine
  • Biomarkers / urine
  • Cisplatin
  • Demography
  • Female
  • Fibrinogen / genetics
  • Fibrinogen / immunology*
  • Fibrinogen / urine*
  • Humans
  • Kidney / immunology*
  • Kidney / pathology*
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nephrosis, Lipoid / complications
  • Nephrosis, Lipoid / pathology
  • Nephrosis, Lipoid / urine
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / complications
  • Reperfusion Injury / pathology
  • Reperfusion Injury / urine
  • Translational Research, Biomedical*
  • Up-Regulation

Substances

  • Biomarkers
  • RNA, Messenger
  • Fibrinogen
  • Cisplatin