title: Urinary active transforming growth factor β in feline chronic kidney disease.
abstract: The cytokine transforming growth factor beta 1 (TGF-β1) has been widely implicated in the development and progression of renal fibrosis in chronic kidney disease (CKD) in humans and in experimental models. The aims of this study were to assess the association between urinary active TGF-β1 and (a) development of CKD in a cross-sectional study, (b) deterioration of renal function over 1 year in a longitudinal study, and (c) renal histopathological parameters in cats. A human active TGF-β1 ELISA was validated for use in feline urine. Cross-sectional analysis revealed no significant difference in urinary active TGF-β1:creatinine ratio (aTGF-β1:UCr) between groups with differing renal function. Longitudinally, non-azotaemic cats that developed CKD demonstrated a significant (P = 0.028) increase in aTGF-β1:UCr approximately 6 months before the development of azotaemia, which remained elevated (P = 0.046) at diagnosis (approximately 12 months prior, 8.4 pg/mg; approximately 6 months prior, 22.2 pg/mg; at CKD diagnosis, 24.6 pg/mg). In the histopathology study, aTGF-β1:UCr was significantly higher in cats with moderate (P = 0.02) and diffuse (P = 0.005) renal fibrosis than in cats without fibrosis. Cats with moderate renal inflammation had significantly higher urinary active aTGF-β1 concentrations than cats with mild (P = 0.035) or no inflammatory change (P = 0.004). The parameter aTGF-β1:UCr was independently associated with Log urine protein:creatinine ratio in a multivariable analysis of clinicopathological parameters and interstitial fibrosis score in a multivariable analysis of histopathological features. These results suggest that urinary aTGF-β1 reflects the severity of renal pathology. Increases in urinary aTGF-β1 followed longitudinally in individual cats may indicate the development of CKD.
authors.affiliation: Comparative Biomedical Sciences, The Royal Veterinary College, Royal College Street, London, NW1 0TU, UK. Electronic address: Jlawson@rvc.ac.uk.
authors.forename: J S
authors.initials: JS
authors.lastname: Lawson
authors.affiliation: Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK.
authors.forename: H M
authors.initials: HM
authors.lastname: Syme
authors.affiliation: Comparative Biomedical Sciences, The Royal Veterinary College, Royal College Street, London, NW1 0TU, UK.
authors.forename: C P D
authors.initials: CP
authors.lastname: Wheeler-Jones
authors.affiliation: Comparative Biomedical Sciences, The Royal Veterinary College, Royal College Street, London, NW1 0TU, UK.
authors.forename: J
authors.initials: J
authors.lastname: Elliott
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine; D002371:Cat Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002415:Cats; D003430:Cross-Sectional Studies; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000662:veterinary*; D007668:Kidney / Q000473:pathology*; D008137:Longitudinal Studies; D008297:Male; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000662:veterinary*; D053773:Transforming Growth Factor beta1 / Q000652:urine*
chemical_list: D015415:Biomarkers; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: Cat; Cytokine; Fibrosis; Renal; Urine