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Originally published online as doi:10.2353/ajpath.2009.080511 on March 5, 2009

Published online before print March 5, 2009
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(American Journal of Pathology. 2009;174:1203-1211.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080511

Urinary L-Type Fatty Acid-Binding Protein Can Reflect Renal Tubulointerstitial Injury

Tamami Tanaka*{dagger}, Kent Doi*{dagger}, Rui Maeda-Mamiya*{dagger}, Kousuke Negishi*{dagger}, Didier Portilla{ddagger}§, Takeshi Sugaya, Toshiro Fujita*{dagger} and Eisei Noiri*{dagger}

From the Departments of Nephrology and Endocrinology,* and Hemodialysis and Apheresis,{dagger} University Hospital, The University of Tokyo, Tokyo, Japan; the Division of Nephrology,{ddagger} the Department of Internal Medicine, University of Arkansas for Medical Science, Little Rock, Arkansas; Central Arkansas Veterans Healthcare Systems,§ Little Rock, Arkansas; and the Center for Developmental Biology, Riken, Kobe, Japan

This study aimed to elucidate the role of L-type fatty acid-binding protein (L-FABP) in renal tubulointerstitial injury using a mouse adenine-induced renal injury model. C57BL/6 mice fed excess dietary adenine for 6 weeks showed a gradual increase in levels of blood urea nitrogen (BUN). They also showed severe tubulointerstitial pathological findings, such as fibrosis and macrophage infiltration without glomerular damage, which were attenuated by treatment with either allopurinol or Y-700, a new xanthine dehydroxygenase inhibitor. Because renal expression of L-FABP is defective in C57BL/6 mice, human L-FABP transgenic mice were fed an adenine-containing diet. Transgenic mice showed lower BUN levels and lower levels of pathological injury compared with wild-type mice. On the other hand, urinary levels and renal expression of L-FABP in the adenine group was significantly increased and attenuated by treatment with either allopurinol or Y-700. Urinary L-FABP was positively correlated with BUN levels and pathological damages in the tubulointerstitium. No increases in urinary protein, albumin, or N-acetyl-β-D-glucosaminidase levels were found for 6 weeks in any group. In conclusion, we demonstrated that urinary L-FABP levels can be used to monitor both dynamics and drug responses in a mouse adenine-induced tubulointerstitial injury model.






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