title: Urinary human L-FABP is a potential biomarker to predict COX-inhibitor-induced renal injury.
abstract: 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.
authors.affiliation: Department of Nephrology and Endocrinology, Tokyo University Hospital, Tokyo, Japan.
authors.forename: Tamami
authors.initials: T
authors.lastname: Tanaka
authors.forename: Eisei
authors.initials: E
authors.lastname: Noiri
authors.forename: Tokunori
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugaya
authors.forename: Kousuke
authors.initials: K
authors.lastname: Negishi
authors.forename: Rui
authors.initials: R
authors.lastname: Maeda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Didier
authors.initials: D
authors.lastname: Portilla
authors.forename: Momokazu
authors.initials: M
authors.lastname: Goto
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: 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
chemical_list: D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins