Urinary collagen degradation products as early markers of progressive renal fibrosis

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-beta receptor, hyaluronan (all P <0.01), iColl3, PAS, myofibroblasts, macrophages and T-cells (all P