Monitoring of urinary L-type fatty acid-binding protein predicts histological severity of acute kidney injury.
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.
Negishi
Kousuke
K
Department of Nephrology and Endocrinology, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, Japan 113-8655.
Noiri
Eisei
E
Doi
Kent
K
Maeda-Mamiya
Rui
R
Sugaya
Takeshi
T
Portilla
Didier
D
Fujita
Toshiro
T
D000818:Animals; D015415:Biomarkers / Q000652:urine; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity; D003432:Cross-Linking Reagents / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000293:injuries* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology*; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012372:ROC Curve; D015427:Reperfusion Injury
D015415:Biomarkers; D003432:Cross-Linking Reagents; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D002945:Cisplatin