Deficiency of Endothelial Progenitor Cells Associates with Graft Thrombosis in Patients Undergoing Endovascular Therapy of Dysfunctional Dialysis Grafts

Abstract

Background: The deficiency of endothelial progenitor cells has been demonstrated to be associated with cardiovascular events in patients undergoing dialysis. However, their correlation with dialysis graft outcomes remains unknown. The objective of this study was to investigate the relationship between circulating endothelial progenitor cells and dialysis graft outcomes.

Methods: After excluding 14 patients with acute coronary syndrome, decompensated heart failure or graft thrombosis in the prior three months, a total of 120 patients undergoing dialysis who underwent endovascular therapy of dysfunctional dialysis grafts were prospectively enrolled. Blood was sampled from study subjects in the morning of a mid-week non-dialysis day. Surface makers of CD34, KDR, and CD133 were used in combination to determine the number of circulating endothelial progenitor cells. All participants were prospectively followed until June 2013.

Results: The median follow-up duration was 13 months, within which 62 patients experienced at least one episode of graft thrombosis. Patients with graft thrombosis had lower CD34⁺KDR⁺ cell counts compared with patients without graft thrombosis (median 4.5 vs. 8 per 10⁵ mononuclear cells, p = 0.02). Kaplan-Meier analysis demonstrated thrombosis-free survival was lower in the low CD34⁺KDR⁺ cell count group (30%) than in the high CD34⁺KDR⁺ cell count group (61%; p = 0.007). Univariate analysis showed diabetes, high sensitive C-reactive protein, lesion length and CD34⁺KDR⁺ cell counts associated with graft thrombosis. Multivariate analyses confirmed an independent association between low CD34⁺KDR⁺ cell counts and graft thrombosis (hazard ratio, 2.52; confidence interval, 1.43-4.44; p = 0.001).

Conclusions: Our study demonstrated an independent association between low circulating endothelial progenitor cell counts and dialysis graft thrombosis.

Keywords: Endothelial progenitor cell; Graft; Hemodialysis; Thrombosis.

Figure 1

Representative flow cytometry analysis. Panels show mononuclear cells (MNCs) that were gated by forward/sideward scatter (FSC/SSC) in isotype controls (A), patients with graft thrombosis (B), and patients without graft thrombosis (C). The numbers of circulating endothelial progenitor cells (EPCs) were defined as CD34+, CD34+KDR+, and CD34+KDR+CD133+, respectively.

Figure 2

Receiver operator characteristic curve of baseline CD34⁺KDR⁺ cell counts for graft thrombosis. The area under receiver operator characteristic curve (AUC) was 0.70 for baseline levels of CD34⁺KDR⁺ cell counts, which was significantly different from a random distribution (dash line, p < 0.001).

Figure 3

Comparisons of the number of endothelial progenitor cells between patients with and without thrombosis.

Figure 4

Kaplan-Meier plots of the thrombosis-free survival stratified by high and low CD34⁺KDR⁺ cell count. The figure demonstrates the proportion of patients without thrombosis of dialysis grafts according to their circulating CD34⁺KDR⁺ cell counts at baseline, stratified by 5.5/10⁵ mononuclear cells into low (dash line) and high (solid line) groups.