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. 2017 Apr 21;12(4):e0175898.
doi: 10.1371/journal.pone.0175898. eCollection 2017.

Non-invasive quantification of collagen turnover in renal transplant recipients

Elisabeth G D Stribos  1   2 , Signe Holm Nielsen  3   4 , Susanne Brix  4 , Morten Asser Karsdal  3 , Marc A Seelen  2 , Harry van Goor  5 , Stephan J L Bakker  2 , Peter Olinga  1 , Henricus A M Mutsaers  1 , Federica Genovese  3
Affiliations

Non-invasive quantification of collagen turnover in renal transplant recipients

Elisabeth G D Stribos et al. PLoS One. .

Abstract

Kidney allograft failure due to chronic injury/rejection remains the main cause of graft loss in renal transplant recipients (RTR). Here, we investigated whether specific biomarkers of extracellular matrix (ECM) turnover are associated with allograft function and chronic kidney disease (CKD) stage in RTR. Seventy-eight patients who attended the University Medical Center Groningen for a routine check-up after kidney transplantation were enrolled in the study. Plasma and/or 24h-urine samples were collected and specific matrix-metalloproteinase-generated neo-epitope fragments of collagens were measured by enzyme-linked immunosorbent assay. Our results demonstrated that urinary levels of C3M, a marker for collagen type III degradation, correlated with estimated glomerular filtration rate (eGFR; r = 0.58, p<0.0001), with lower levels detected in the urine of patients with advanced CKD. In addition, plasma levels of Pro-C6, a marker for collagen type VI formation, significantly increased with disease progression and correlated with eGFR (r = -0.72, p<0.0001). Conversely, plasma C3M and urinary Pro-C6 levels showed no correlation with renal function. We identified two neo-epitope biomarkers of tissue turnover associated with ECM remodeling and fibrosis that can stratify patients by CKD stage. This is as promising first step towards non-invasive monitoring of ECM turnover in the kidneys.

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Conflict of interest statement

Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: SHN, FG and MAK are full-time employees at Nordic Bioscience. All other authors have no competing financial interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Associations between estimated glomerular filtration rate (eGFR) and biomarkers for ECM remodeling in urine and plasma.
Correlations of creatinine-normalized urinary C3M (uC3M/creatinine) (A) and plasma C3M (pC3M) (B) with eGFR in RTR.
Fig 2
Fig 2. Associations between estimated glomerular filtration rate (eGFR) and biomarkers for ECM remodeling in urine and plasma.
Correlations of urinary uPro-C6 normalized to creatinine (uPro-C6/creatinine) (A) and plasma Pro-C6 (pPro-C6) (B) with eGFR in RTR.
Fig 3
Fig 3. Representative images of collagen type VI staining in healthy and fibrotic renal tissue.
Magnification 200x for collagen VI staining and 100x for PSR staining. PSR, Picro-Sirius Red.
See this image and copyright information in PMC

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