Serum and urine markers of collagen degradation reflect renal fibrosis in experimental kidney diseases

Nephrol Dial Transplant. 2015 Jul;30(7):1112-21. doi: 10.1093/ndt/gfv063. Epub 2015 Mar 16.


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.

Keywords: biomarkers; interstitial fibrosis; rat models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis*
  • Collagen Type I / blood*
  • Collagen Type I / urine*
  • Collagen Type III / blood*
  • Collagen Type III / urine*
  • Disease Models, Animal
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Fibrosis / blood
  • Fibrosis / diagnosis*
  • Fibrosis / etiology
  • Fibrosis / urine
  • Immunoenzyme Techniques
  • Kidney Diseases / complications*
  • Kidney Diseases / surgery
  • Male
  • Nephrectomy / adverse effects*
  • Rats
  • Rats, Inbred F344


  • Biomarkers
  • Collagen Type I
  • Collagen Type III