Background: The release of surface-derived microvesicles (MV) is a common phenomenon of cellular activation and occurs specifically as a consequence of terminal complement complex assembly on cellular surfaces. Increased counts of endothelial- and platelet-derived MV have been found in patient plasma in various pathological conditions and have been implicated in disease pathogenesis promoting microvascular injury. We hypothesized that MV counts and the pattern of complement fragment deposition on plasma MV in patients after renal transplantation would be indicative of microvascular injury and identify patients undergoing allograft rejection.

Methods: Plasma from 20 patients undergoing renal transplantation was analyzed for the presence of platelet (CD41+ AnnexinV+) and endothelial (CD146+) MV as well as deposition of C3 fragments and the terminal complement complex C5b-9 on MV by flow cytometry before, immediately after reperfusion and on days 1, 7, 28 and 90 following transplantation. Protocol biopsies were obtained on days 7 and 90.

Results: Median creatinine was 133 [micro]mol/l (range 72-232 [micro]mol/l) at day 90. During the first three months following transplantation, there were four episodes of T-cell-mediated rejection (defined as BANFF 2007 classification 4.I or 4.II) and five patients with microvascular injury (ptc≥1) on renal biopsy. Compared to healthy controls, patient plasma analysis prior to transplantation revealed increased numbers of platelet and endothelial MV (median 37.5×10⁵/ml vs. 13.9×10⁵/ml and 6.5×10⁴/ml vs. 1.6×10⁴/ml, respectively) as well as an increase in C3 fragment deposition on platelet MV (mean fluorescence intensity (MFI) 1576 vs. 328). Following transplantation, neither platelet MV counts nor MFI of C3 fragment deposition were predictive or indicative of allograft rejection. However, we found increased numbers of CD146+ endothelial MV at the time of cellular rejection (median 9.1×10⁴/ml, n=3) compared to negative biopsies (3.5×10⁴/ml, n=17) that were further increased in patients displaying signs of microvascular injury (11.1×10⁴/ml, n=5, p<0.01 by Kruskal-Wallis test). Analysis of C5b-9 deposition on endothelial MV is ongoing.

Conclusion: Plasma endothelial MV counts might be indicative of allograft rejection.

CITATION INFORMATION: Zecher D, Cumpelik A, Ruhland B, Banas B, Hopfer H, Dickenmann M, Schifferli J. Plasma Endothelial Microvesicle Counts Indicate Allograft Rejection Following Kidney Transplantation. Am J Transplant. 2016;16 (suppl 3).

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