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

Manuela Yepes-Calderón, Camilo G Sotomayor*, Daniel Guldager Kring Rasmussen, Ryanne S Hijmans, Charlotte A Te Velde-Keyzer, Marco van Londen, Marja van Dijk, Arjan Diepstra, Stefan P Berger, Morten Asser Karsdal, Frederike J Bemelman, Johan W de Fijter, Jesper Kers, Sandrine Florquin, Federica Genovese, Stephan J L Bakker, Jan-Stephan Sanders, Jacob Van Den Born

*Bijbehorende auteur voor dit werk

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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.

Originele taal-2English
Aantal pagina's12
TijdschriftJournal of Clinical Medicine
Nummer van het tijdschrift10
StatusPublished - okt-2020

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