title: Serum and urine markers of collagen degradation reflect renal fibrosis in experimental kidney diseases.
abstract: BACKGROUND
  The extent of renal fibrosis in chronic kidney disease (CKD) is the best predictor for progression of most renal diseases. To date, no established biomarkers of renal fibrosis exist.
  
  
  METHODS
  We measured circulating and urinary-specific matrix metalloproteinase (MMP)-generated collagen type I and III degradation fragments (C1M and C3M) and an N-terminal propeptide of collagen III (Pro-C3), as markers of collagen type III production, in three rat models of CKD and fibrosis: renal mass reduction (5/6 nephrectomy), progressive glomerulonephritis (chronic anti-Thy1.1 nephritis) and adenine crystal-induced nephropathy. Healthy rats served as controls.
  
  
  RESULTS
  In all three models, the animals developed significant CKD and renal fibrosis. Compared with healthy rats, serum C1M and C3M significantly increased in rats with 5/6 nephrectomy and adenine nephropathy (2- to 3-fold), but not with chronic anti-Thy1.1 nephritis. Urinary C1M and C3M levels increased 9- to 100-fold in all three models compared with controls. Urinary degradation markers correlated closely with renal deposition of collagen type I and type III. Pro-C3 was significantly increased only in the urine of 5/6 nephrectomy rats.
  
  
  CONCLUSIONS
  In particular, urinary markers of MMP-driven collagen degradation, rather than collagen production markers, may represent a novel, specific and non-invasive diagnostic approach to assess kidney fibrosis.
authors.affiliation: Institute of Pathology, RWTH University of Aachen, Aachen, NRW, Germany Department of Nephrology, RWTH University of Aachen, Aachen, NRW, Germany Department of Nephrology, University Hospital of Patras, Patras, Greece.
authors.forename: Marios
authors.initials: M
authors.lastname: Papasotiriou
authors.affiliation: Nordic Bioscience, 2730 Herlev, Denmark.
authors.forename: Federica
authors.initials: F
authors.lastname: Genovese
authors.affiliation: Institute of Pathology, RWTH University of Aachen, Aachen, NRW, Germany.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Klinkhammer
authors.affiliation: Department of Nephrology, RWTH University of Aachen, Aachen, NRW, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Kunter
authors.affiliation: Nordic Bioscience, 2730 Herlev, Denmark.
authors.forename: Signe H
authors.initials: SH
authors.lastname: Nielsen
authors.affiliation: Nordic Bioscience, 2730 Herlev, Denmark.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Department of Nephrology, RWTH University of Aachen, Aachen, NRW, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: Institute of Pathology, RWTH University of Aachen, Aachen, NRW, Germany Department of Nephrology, RWTH University of Aachen, Aachen, NRW, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Boor
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D024042:Collagen Type I / Q000097:blood* / Q000652:urine*; D024061:Collagen Type III / Q000097:blood* / Q000652:urine*; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D007124:Immunoenzyme Techniques; D007674:Kidney Diseases / Q000150:complications* / Q000601:surgery; D008297:Male; D009392:Nephrectomy / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D024061:Collagen Type III
keywords: biomarkers; interstitial fibrosis; rat models