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Urinary Human L-FABP Is a Potential Biomarker to Predict COX-Inhibitor-Induced Renal InjuryTanaka T.a · Noiri E.a, d · Yamamoto T.b · Sugaya T.c · Negishi K.a · Maeda R.d · Nakamura K.c · Portilla D.e · Goto M.b · Fujita T.a
aDepartments of Nephrology and Endocrinology and Hemodialysis and Apheresis, Tokyo University Hospital, Tokyo, bDepartment of Urology, Nagoya University Hospital, Nagoya, cCMIC Co. Ltd., Tokyo, and dCenter for NanoBio Integration, University of Tokyo, Tokyo, Japan; eDivision of Nephrology, Department of Internal Medicine, University of Arkansas for Medical Sciences and Central Veteran Healthcare System, Little Rock, Ark., USA
Background/Aim: 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. Conclusion: Urinary L-FABP is capable of revealing chronic renal injury induced by COX inhibitors.
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