Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial

Yepes-Calderón, M., Sotomayor, C. G., Rasmussen, D. G. K., Hijmans, R. S., Te Velde-Keyzer, C. A., van Londen, M., van Dijk, M., Diepstra, A., Berger, S. P., Karsdal, M. A., Bemelman, F. J., de Fijter, J. W., Kers, J., Florquin, S., Genovese, F., Bakker, S. J. L., Sanders, J-S. & Van Den Born, J., Oct-2020, In : Journal of Clinical Medicine. 9, 10, 12 p., 3216.

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The PRO-C6 assay, a reflection of collagen type VI synthesis, has been proposed as a non-invasive early biomarker of kidney fibrosis. We aimed to investigate cross-sectional and longitudinal associations between plasma and urine PRO-C6 and proven histological changes after kidney transplantation. The current study is a post-hoc analysis of 94 participants of the MECANO trial, a 24-month prospective, multicenter, open-label, randomized, controlled trial aimed at comparing everolimus-based vs. cyclosporine-based immunosuppression. PRO-C6 was measured in plasma and urine samples collected 6 and 24 months post-transplantation. Fibrosis was evaluated in biopsies collected at the same time points by Banff interstitial fibrosis/tubular atrophy (IF/TA) scoring and collagen staining (Picro Sirius Red; PSR); inflammation was evaluated by the tubulo-interstitial inflammation score (ti-score). Linear regression analyses were performed. Six-month plasma PRO-C6 was cross-sectionally associated with IF/TA score (Std. beta = 0.34), and prospectively with 24-month IF/TA score and ti-score (Std. beta = 0.24 and 0.23, respectively) (p <0.05 for all). No significant associations were found between urine PRO-C6 and any of the biopsy findings. Fibrotic changes and urine PRO-C6 behaved differentially over time according to immunosuppressive therapy. These results are a first step towards non-invasive fibrosis detection after kidney transplantation by means of collagen VI synthesis measurement, and further research is required.

Original languageEnglish
Article number3216
Number of pages12
JournalJournal of Clinical Medicine
Issue number10
Publication statusPublished - Oct-2020


  • kidney transplantation, fibrosis, inflammation, extracellular matrix, collagen type VI, FIBROSIS

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