Monitoring of urinary L-type fatty acid-binding protein predicts histological severity of acute kidney injury

Am J Pathol. 2009 Apr;174(4):1154-9. doi: 10.2353/ajpath.2009.080644. Epub 2009 Mar 5.

Abstract

The present study aimed to evaluate whether levels of urinary L-type fatty acid-binding protein (L-FABP) could be used to monitor histological injury in acute kidney injury (AKI) induced by cis-platinum (CP) injection and ischemia reperfusion (IR). Different degrees of AKI severity were induced by several renal insults (CP dose and ischemia time) in human L-FABP transgenic mice. Renal histological injury scores increased with both CP dose and ischemic time. In CP-induced AKI, urinary L-FABP levels increased exponentially even in the lowest dose group as early as 2 hours, whereas blood urea nitrogen (BUN) levels increased at 48 hours. In IR-induced AKI, BUN levels increased only in the 30-minute ischemia group 24 hours after reperfusion; however, urinary L-FABP levels increased more than 100-fold, even in the 5-minute ischemia group after 1 hour. In both AKI models, urinary L-FABP levels showed a better correlation with final histological injury scores and glomerular filtration rates measured by fluorescein isothiocyanate-labeled inulin injection than with levels of BUN and urinary N-acetyl-D-glucosaminidase, especially at earlier time points. Receiver operating characteristic curve analysis demonstrated that urinary L-FABP was superior to other biomarkers for the detection of significant histological injuries and functional declines. In conclusion, urinary L-FABP levels are better suited to allow the accurate and earlier detection of both histological and functional insults in ischemic and nephrotoxin-induced AKI compared with conventional renal markers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomarkers / urine
  • Cisplatin / administration & dosage
  • Cisplatin / toxicity
  • Cross-Linking Reagents / administration & dosage
  • Cross-Linking Reagents / toxicity
  • Dose-Response Relationship, Drug
  • Fatty Acid-Binding Proteins / genetics
  • Fatty Acid-Binding Proteins / urine*
  • Humans
  • Kidney / injuries*
  • Kidney / pathology
  • Kidney Diseases / chemically induced
  • Kidney Diseases / pathology*
  • Kidney Function Tests
  • Male
  • Mice
  • Mice, Transgenic
  • ROC Curve
  • Reperfusion Injury

Substances

  • Biomarkers
  • Cross-Linking Reagents
  • FABP1 protein, human
  • Fatty Acid-Binding Proteins
  • Cisplatin