Urinary L-type fatty acid-binding protein can reflect renal tubulointerstitial injury.

Abstract

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-beta-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.

• Authors: Tamami Tanaka, Kent Doi, Rui Maeda-Mamiya, Kousuke Negishi, Didier Portilla, Takeshi Sugaya, Toshiro Fujita, Eisei Noiri
• Journal: The American journal of pathology (Am J Pathol) Vol. 174 Issue 4 Pg. 1203-11 (Apr 2009) ISSN: 1525-2191 [Electronic] United States
• PMID: 19264908 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• 1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid
• Biomarkers
• Ccl2 protein, mouse
• Chemokine CCL2
• Enzyme Inhibitors
• Fabp1 protein, mouse
• Fatty Acid-Binding Proteins
• Pyrazoles
• Transforming Growth Factor beta1
• Allopurinol

Topics

• Allopurinol (therapeutic use)
• Animals
• Biomarkers (urine)
• Blood Urea Nitrogen
• Blotting, Western
• Chemokine CCL2 (metabolism)
• Enzyme Inhibitors (therapeutic use)
• Enzyme-Linked Immunosorbent Assay
• Fatty Acid-Binding Proteins (genetics, urine)
• Humans
• Kidney Diseases (drug therapy, urine)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Pyrazoles (therapeutic use)
• Reverse Transcriptase Polymerase Chain Reaction
• Transforming Growth Factor beta1 (metabolism)