Abstract
L-type Fatty Acid Binding Protein(L-FABP), which is located in the cytoplasm of renal proximal tubular cells, responses to ischemia and oxidative stress and is excreted in urine. We have reported L-FABP is also very useful as a toxicological renal biomarker in animal models of acute kidney injury (AKI). The purpose of this research was to evaluate urinary L-FABP with other 7 urine biomarkers (Clusterin, KIM-1, NGAL, Osteopontin, NAG, β2M and Cystatin C) in adenine-induced CKD rat model. Adenine was administered orally to male Sprague-Dawley rats at doses of 0, 40, 70 or 100 mg/kg /day for 7 days, or at 0, 25, 100 or 250 mg/kg/day for 28 days. Serum and urinary biomarkers were measured on Days 1, 8, 15, 22 or 29, and the histopathological examination was performed in the kidney on Days 8, 15 or 29.
As a result, on Day 1 (next day of the first dosing), urinary L-FABP and Clusterin elevated at adenine of 70 mg/kg, but conventional renal biomarkers as blood urea nitrogen (BUN) and serum creatinine (SCr) were not changed. By Day 8, Kim-1 and NAG elevated. On Day 28, L-FABP, NGAL, Kim-1, Osteopontin, NAG and Clusterin were significantly increased in a dose-dependent manner with accompanying severe proximal tubule damages, but other urinary biomarkers were not changed. In addition, BUN and SCr elevated at more than 100 mg/kg after Day 8.
These results suggest that the urinary L-FABP is one of the most sensitive biomarker for detecting proximal tubule damage in adenine-induced CKD model rats. Furthermore, urinary L-FABP and other novel biomarkers would predict the CKD progression.
