NDT Advance Access published online on January 22, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn755
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Circulating angiopoietin-2 is a marker and potential mediator of endothelial cell detachment in ANCA-associated vasculitis with renal involvement
1 Department of Nephrology and Hypertension, Hannover Medical School 2 Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg Strasse 1, D-30625, Hannover, Germany
Correspondence and offprint requests to: Philipp Kümpers, Department of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Tel: +49-511-532-6319; Fax: +49-511-552366; E-mail: kuempers.philipp{at}mh-hannover.de
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Abstract |
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Background. The endothelial-specific angiopoietin (Ang)-Tie ligand–receptor system has been identified as a non-redundant regulator of endothelial cell detachment in vitro. Binding of circulating angiopoietin-2 (Ang-2) to the Tie2 receptor antagonizes Tie2 signalling and leads to disassembly of cell–cell junctions. Here, we ask whether circulating Ang-2 correlates with the severity of endothelial damage in ANCA-associated vasculitis (AAV) with renal involvement.
Methods. Ang-2 was measured in sera obtained from 45 patients with AAV and 20 healthy controls by in-house ELISA. The disease activity was monitored by BVAS and the enumeration of circulating endothelial cells (CECs).
Results. Ang-2 was significantly elevated in active AAV with renal involvement compared to controls and patients in remission. In contrast, Ang-2 was normal in patients with active granulomatous disease limited to the respiratory tract. Linear regression analysis demonstrated a strong association of Ang-2 with BVAS (rs2 = 0.49 P < 0.0001) and the number of CECs (rs2 = 0.48 P < 0.001). An Ang-2 cut-off value >4.15 ng/ml for a positive result yielded 100% specificity and 65% sensitivity for active systemic vasculitis. The positive predictive value was 99% and the negative predictive value 84%.
Conclusions. Circulating Ang-2 is elevated and closely correlates with BVAS and CEC numbers in AAV with renal involvement. These data indicate that Ang-2 might be a potential mediator of endothelial cell detachment in AAV.
Keywords: ANCA-associated vasculitis; angiopoietin-2; circulating endothelial cells; disease activity; necrotizing glomerulonephritis
* These authors contributed equally to the manuscript and are both considered first authors
Received for publication: 29.10.08
Accepted in revised form: 15.12.08