Frontiers in Transplantation · Published 2026-06-11 · DOI 10.3389/frtra.2026.1812847
Edwin O. W. Bredewold, Rudmer J. Postma, Joe Chan, My H. S. Svensson, Annette Bruchfeld, Johannes W. de Fijter, Hans Furuland, Anders Hartmann, Lars Mjornstedt, Karin Skov, Inga soveri, Soeren S. Sorensen, Bengt Fellstrom, Jacques M. Duijs, Roel Bijkerk, Joris I. Rotmans, Anton-Jan van Zonneveld
IntroductionSide effects of calcineurin inhibitors (CNI) comprise hypertension, diabetes and nephrotoxicity, and endothelial dysfunction (ED) has often been implicated. Belatacept, a co-stimulation blocker, may offer a more favourable vascular profile.MethodsWe investigated markers of endothelial function in blood samples from kidney transplant recipients (KTR) that were converted from CNI to belatacept. We assessed established markers of ED including soluble thrombomodulin, P-selectin and angiopoietin 1 and 2. In addition, we assessed expression levels of microRNAs (miRNAs), which have been identified as discriminative markers for ED, rejection and renal fibrosis in the setting of transplantation. Lastly, we used patient samples and CNI-dilution series in a validated model of ED in which changes in morphological characteristics of endothelial cells were evaluated.ResultsUnexpectedly, we found no differences in our assays between both groups. We did observe dose-related effects of CNI on endothelial cell (EC) morphology upon direct exposure of EC to tacrolimus and ciclosporin A, but a similar effect was not seen when plasma samples of KTR who were converted to belatacept were compared with samples from KTR on CNI's.DiscussionThese data suggest that CNI-side-effects bundled under the term “CNI-toxicity” are not derived from a significant clinical effect of CNI on endothelial function.
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Bredewold, E., Postma, R., Chan, J., et al. (2026). An exploration of markers of microvascular dysfunction in kidney transplant recipients randomized to belatacept: no clinical impact of CNIs on endothelial function. Frontiers in Transplantation. https://doi.org/10.3389/frtra.2026.1812847