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Bijkerk R, Florijn BW, Khairoun M, et al. Acute Rejection After Kidney Transplantation Associates With Circulating MicroRNAs and Vascular Injury. Transplant Direct. 2017;3(7):e174doi: 10.1097/TXD.0000000000000699.
Bijkerk, R., Florijn, B. W., Khairoun, M., Duijs, J. M. G. J., Ocak, G., de Vries, A. P. J., Schaapherder, A. F., Mallat, M. J. K., de Fijter, J. W., Rabelink, T. J., van Zonneveld, A. J., & Reinders, M. E. J. (2017). Acute Rejection After Kidney Transplantation Associates With Circulating MicroRNAs and Vascular Injury. Transplantation direct, 3(7), e174. https://doi.org/10.1097/TXD.0000000000000699
Bijkerk, Roel, et al. "Acute Rejection After Kidney Transplantation Associates With Circulating MicroRNAs and Vascular Injury." Transplantation direct vol. 3,7 (2017): e174. doi: https://doi.org/10.1097/TXD.0000000000000699
Bijkerk R, Florijn BW, Khairoun M, Duijs JMGJ, Ocak G, de Vries APJ, Schaapherder AF, Mallat MJK, de Fijter JW, Rabelink TJ, van Zonneveld AJ, Reinders MEJ. Acute Rejection After Kidney Transplantation Associates With Circulating MicroRNAs and Vascular Injury. Transplant Direct. 2017 Jun 19;3(7):e174. doi: 10.1097/TXD.0000000000000699. eCollection 2017 Jul. PMID: 28706977; PMCID: PMC5498015.
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Transplant Direct. 2017 Jun 19;3(7):e174. doi: 10.1097/TXD.0000000000000699. eCollection 2017 Jul.

Acute Rejection After Kidney Transplantation Associates With Circulating MicroRNAs and Vascular Injury.

Transplantation direct

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

Affiliations

  1. Department of Internal Medicine (Nephrology), Leiden University Medical Center, The Netherlands.
  2. Einthoven Laboratory for Experimental Vascular Research, Leiden University Medical Center, The Netherlands.
  3. Department of Clinical Epidemiology, Leiden University Medical Center, The Netherlands.
  4. Department of Surgery, Leiden University Medical Center, The Netherlands.

PMID: 28706977 PMCID: PMC5498015 DOI: 10.1097/TXD.0000000000000699

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.

Conflict of interest statement

The authors declare no conflicts of interest.

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