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

Yepes-Calderon, Manuela; Sotomayor, Camilo G.; Rasmussen, Daniel Guldager Kring; Hijmans, Ryanne S.; Velde-Keyzer, Charlotte A. Te; van Londen, Marco; van Dijk, Marja; Diepstra, Arjan; Berger, Stefan P.; Karsdal, Morten Asser; Bemelman, Frederike J.; de Fijter, Johan W.; Kers, Jesper; Florquin, Sandrine; Genovese, Federica; et. al.

Abstract

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.

Más información

Título según WOS: ID WOS:000586200600001 Not found in local WOS DB
Título de la Revista: JOURNAL OF CLINICAL MEDICINE
Volumen: 9
Número: 10
Editorial: MDPI
Fecha de publicación: 2020
DOI:

10.3390/jcm9103216

Notas: ISI