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: Marios Papasotiriou, Federica Genovese, Barbara M Klinkhammer, Uta Kunter, Signe H Nielsen, Morten A Karsdal, Jürgen Floege, Peter Boor
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 30 Issue 7 Pg. 1112-21 (Jul 2015) ISSN: 1460-2385 [Electronic] England
• PMID: 25784725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Chemical References

• Biomarkers
• Collagen Type I
• Collagen Type III

Topics

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