Non-invasive quantification of collagen turnover in renal transplant recipients

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


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.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • Cohort Studies
  • Collagen / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Kidney Transplantation*
  • Male
  • Middle Aged


  • Biomarkers
  • Collagen

Grant support

This work was supported by the Danish Research Fund (Den Danske Forskningsfond) and the Netherlands Organization for Health Research and Development (ZonMw; grant number 114021010, PO). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.