Acute Rejection after Kidney Transplantation Associates with Circulating MicroRNAs and Vascular Injury

Roel Bijkerk*, Barend W. Florijn, Meriem Khairoun, Jacques M.G.J. Duijs, Gurbey Ocak, Aiko P.J. de Vries, Alexander F. Schaapherder, Marko J.K. Mallat, Johan W. de Fijter, Ton J. Rabelink, Anton Jan van Zonneveld, Marlies E.J. Reinders

*Corresponding author for this work

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Abstract

Background. Acute rejection (AR) of kidney transplants is associated with the loss of endothelial integrity, microvascular rarefaction and, ultimately, graft dysfunction. Circulating angiogenic microRNAs (miRNAs) may serve as markers for microvascular injury. Here, we investigated the short- and long-term effects of AR after kidney transplantation on systemic vascular injury and the associated circulating miRNA profile. Methods. Systemic vascular injury was determined by measuring capillary tortuosity and density within the oral mucosa as well as by assessing circulating levels of angiopoietin-2/angiopoietin-1 ratio, vascular endothelial growth factor and soluble thrombomodulin. After a pilot study, we selected 48 miRNAs to assess the AR- and microvascular injury associated circulating miRNAs. Results. In stable transplant recipients (n = 25) and patients with AR (n = 13), which were also studied longitudinally (1, 6, and 12 months post-AR), we found an AR-associated increase in markers of systemic vascular injury, of which vascular endothelial growth factor and soluble thrombomodulin normalized within 1 year after AR. Of the 48 selected miRNAs, 8 were either decreased (miR-135a, miR-199a-3p, and miR-15a) or increased (miR-17, miR-140-3p, miR-130b, miR-122 and miR-192) in AR. Of these, miR-130b, miR-199a, and miR-192 associated with markers of vascular injury, whereas miR-140-3p, miR-130b, miR-122, and miR-192 normalized within 1 year after AR. Conclusions. AR after kidney transplantation is characterized by systemic microvascular injury and associates with specific circulating miRNA levels.

Original languageEnglish
Pages (from-to)E174
JournalTransplantation Direct
Volume3
Issue number7
DOIs
Publication statusPublished - 1 Jul 2017
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by a Veni grant from ZonMW (01086089) to M.E.J. Reinders and grants from the Dutch Heart Foundation (Queen of Hearts: Improving diagnosis of CVD in women; 2013T084), the Dutch kidney foundation (NSN 14OI13) and the European Foundation for the study of Diabetes to A.J. van Zonneveld and R. Bijkerk.


Publisher Copyright:
Copyright © 2017 The Author(s).

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