Urinary human L-FABP is a potential biomarker to predict COX-inhibitor-induced renal injury.
OBJECTIVE
A strong demand exists for the development of sensitive biomarkers in the nephrology field. We propose urinary human L-type fatty acid binding protein (L-FABP) as an earlier biomarker to detect the outcome of chronic renal injury induced by cyclooxygenase (COX) inhibitors using human L-FABP transgenic mice.


METHODS
After consuming a low-sodium diet for 2 weeks, transgenic mice were administered meloxicam or celecoxib with the low-sodium diet. Mice were sacrificed 2 days and 4 weeks after starting COX inhibitors, and urine was collected 24 and 48 h and 1, 2, 3, and 4 weeks after starting COX inhibitors. Celecoxib-treated mice were divided into responders or nonresponders according to urinary L-FABP levels, and histology, urinary L-FABP and peritubular capillary blood flow were evaluated.


RESULTS
Meloxicam-treated mice showed a higher blood pressure than control mice. Urinary L-FABP was significantly increased in COX inhibitor-treated mice. Peritubular capillary blood flow in all meloxicam-treated mice and in some celecoxib-treated mice was significantly decreased. Although blood urea nitrogen was not increased, interstitial fibrosis and macrophage infiltration were revealed, especially in meloxicam-treated mice. Responders showed an increase of fibrotic areas and correlations between urinary L-FABP and peritubular capillary blood flow.


CONCLUSIONS
Urinary L-FABP is capable of revealing chronic renal injury induced by COX inhibitors.
Tanaka
Tamami
T
Department of Nephrology and Endocrinology, Tokyo University Hospital, Tokyo, Japan.
Noiri
Eisei
E
Yamamoto
Tokunori
T
Sugaya
Takeshi
T
Negishi
Kousuke
K
Maeda
Rui
R
Nakamura
Kazuo
K
Portilla
Didier
D
Goto
Momokazu
M
Fujita
Toshiro
T
D000818:Animals; D015415:Biomarkers / Q000652:urine; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000652:urine*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D011237:Predictive Value of Tests
D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins