Urinary collagen degradation products as early markers of progressive renal fibrosis.

Autor: Hijmans RS; Division of Nephrology, Department of Medicine, University Medical Center Groningen, Groningen, The Netherlands. r.s.hijmans@umcg.nl., Rasmussen DG; Nordic Bioscience, Biomarkers & Research, Herlev, Denmark.; Institute of Molecular Medicine, Cardiovascular and Renal Research, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark., Yazdani S; Division of Nephrology, Department of Medicine, University Medical Center Groningen, Groningen, The Netherlands., Navis G; Division of Nephrology, Department of Medicine, University Medical Center Groningen, Groningen, The Netherlands., van Goor H; Division of Pathology, Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands., Karsdal MA; Nordic Bioscience, Biomarkers & Research, Herlev, Denmark., Genovese F; Nordic Bioscience, Biomarkers & Research, Herlev, Denmark., van den Born J; Division of Nephrology, Department of Medicine, University Medical Center Groningen, Groningen, The Netherlands.
Jazyk: angličtina
Zdroj: Journal of translational medicine [J Transl Med] 2017 Mar 20; Vol. 15 (1), pp. 63. Date of Electronic Publication: 2017 Mar 20.
DOI: 10.1186/s12967-017-1163-2
Abstrakt: Background: Renal fibrogenesis is associated with increased ECM remodeling and release of collagen fragments in urine in progressive renal disease. We investigated the diagnostic value of urinary collagen degradation products in a proteinuria-driven fibrosis rat model with and without anti-fibrotic S1P-receptor modulator FTY720 treatment.
Methods: Proteinuria was induced in male Wistar rats by Adriamycin (ADR) injection (n = 16). Healthy rats served as controls (n = 12). Six weeks post-injection, all underwent renal biopsy, and FTY720-treatment started in ADR-rats (n = 8) and controls (n = 6). Others remained untreated. Rats were sacrificed after 12 weeks. Collagen type I (C1M) and III (C3M) degradation fragments were measured in blood and urine using ELISA. Kidneys were stained for various inflammatory and fibrotic markers.
Results: Six weeks post-injection proteinuria increased (versus controls, P < 0.001) and although no accumulation of interstitial renal collagen type III (iColl3) was observed at this time, urinary C3M (uC3M) and C1M (uC1M) were significantly increased (both P < 0.001). At 12 weeks, uC3M (P < 0.001) and uC1M (P < 0.01) further increased in ADR-rats versus controls, just as fibronectin, PDGF-β receptor, hyaluronan (all P < 0.01), iColl3, PAS, myofibroblasts, macrophages and T-cells (all P < 0.05). FTY720-treatment reduced accumulation of immune cells, α-SMA+ myofibroblasts and PAS-score, but not iColl3 and uC3M. Correlation analyses indicated that uC3M and uC1M reflected and predicted tubulointerstitial fibrogenesis.
Conclusions: These data displayed urinary collagen breakdown products as sensitive early markers of interstitial fibrosis, preceding histological fibrotic changes, which might replace the invasive renal biopsy procedure to assess fibrosis. Anti-fibrotic FTY720 intervention reduced some fibrotic markers without affecting collagen type III metabolism.
Databáze: MEDLINE
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