Monitoring of Urinary L-Type Fatty Acid-Binding Protein Predicts Histological Severity of Acute Kidney Injury

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 CPinduced 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 Acute kidney injury (AKI) is still a critical problem because the mortality rate of severely ill patients complicated with AKI is much higher than non-AKI patients. 1There is no effective treatment for human AKI except for supportive renal replacement therapy such as dialysis. Novel renal biomarkers are indispensable to develop a new therapeutic strategy for AKI because it will allow us to detect AKI and start treatment early.2 In addition to early detection, renal biomarkers should be able to estimate renal injury accurately. Because acute tubular necrosis (ATN) is the common feature of most AKI, predicting histological injuries in renal tubular cells would be one of the required characteristics of renal biomarkers in AKI.We have recently demonstrated that L-type fatty acidbinding protein (L-FABP) is localized to proximal tubular cells in human kidney and projected to urinary space after ischemia reperfusion (IR) injury in living-related kidney transplantation.3 In human AKI after cardiac surgery, urinary L-FABP levels were increased at 4 hours after surgery in AKI patients at least, whereas serum creatinine started to increase 48 hours later.4 Mouse L-FABP in proximal tubules of C57BL/6 wild-type mice was virtually defective because of the silencing sequence localizing in the upstream of the promoter region. Therefore, we used human L-FABP transgenic mice, which are humanized by expressing higher protein levels of human L-FABP in

Early Biomarkers of Renal Injury

“…In L-FABP transgenic mice, urinary L-FABP levels allowed the accurate and earlier detection of both histologic and functional insults in ischemia-induced AKI. 60 In contrast, heart-type FABP (H-FABP) is localized in the distal tubules, heart, small intestine, and skeletal muscles.…”

Urinary early kidney injury molecules in children with beta-thalassemia major

“…Recent studies performed in children have shown that L-FABP is a sensitive biomarker in ischemic renal injury. 15 Few data are available regarding renal functional abnormalities in children with thalassemia. 2 There are very few studies that investigate renal dysfunction in patients with TM.…”

Reduction of Tubular Flow Rate as a Mechanism of Oliguria in the Early Phase of Endotoxemia Revealed by Intravital Imaging

“…Total GFR was measured by plasma decay kinetics of FITC-inulin. 47,48 A bolus of around 4 ml/g body wt FITC-inulin was injected into the retro-orbital plexus of either vehicle-injected mice or LPS-injected mice, and blood was collected 1, 3, 5, 10, 15, 35, 55, and 75 minutes later. Plasma fluorescence was measured using a microplate reader (SH-9000; Corona, Ibaraki, Japan).…”