TY - JOUR
T1 - Biopsy-controlled non-invasive quantification of collagen type VI in kidney transplant recipients: A post-hoc analysis of the mecano trial
AU - Yepes-Calderón, Manuela
AU - Sotomayor, Camilo G.
AU - Rasmussen, Daniel Guldager Kring
AU - Hijmans, Ryanne S.
AU - te Velde-Keyzer, Charlotte A.
AU - van Londen, Marco
AU - van Dijk, Marja
AU - Diepstra, Arjan
AU - Berger, Stefan P.
AU - Karsdal, Morten Asser
AU - Bemelman, Frederike J.
AU - de Fijter, Johan W.
AU - Kers, Jesper
AU - Florquin, Sandrine
AU - Genovese, Federica
AU - Bakker, Stephan J. L.
AU - Sanders, Jan-Stephan
AU - van den Born, Jacob
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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. β = 0.34), and prospectively with 24-month IF/TA score and ti-score (Std. β = 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.
AB - 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. β = 0.34), and prospectively with 24-month IF/TA score and ti-score (Std. β = 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85114270463&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/33036366
U2 - https://doi.org/10.3390/jcm9103216
DO - https://doi.org/10.3390/jcm9103216
M3 - Article
C2 - 33036366
SN - 2077-0383
VL - 9
SP - 1
EP - 12
JO - Journal of clinical medicine
JF - Journal of clinical medicine
IS - 10
ER -