Published Online
on January 20, 2003

A more recent version of this article appeared on March 1, 2003

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Submitted on September 19, 2002
Revised on November 12, 2002

Circulating Endothelial Cells Are a Novel Marker of Cyclosporine-Induced Endothelial Damage

Alexander Woywodt; Maik Schroeder; Michael Mengel; Anke Schwarz; Wilfried Gwinner; Hermann Haller; and Marion Haubitz^*

From the Division of Nephrology, Institute for Pathology (M.M.), Medical School, Hannover, Germany.

^* To whom correspondence should be addressed. E-mail: Haubitz.Marion{at}MH-Hannover.de.

Abstract--Microvascular endothelial cells play a key role in transplant immunology. They are also important targets for calcineurin inhibitors. We recently demonstrated elevated numbers of circulating endothelial cells in renal transplant recipients with and without rejection in comparison with healthy controls. Because these patients received either cyclosporine or tacrolimus, we speculated that endothelial damage from calcineurin inhibitors might be responsible for these findings. In the present study, we tested the hypothesis that treatment with calcineurin inhibitors leads to an increase in circulating endothelial cells. We studied 57 renal transplant recipients: 19 on a calcineurin inhibitor-free immunosuppressive regimen and 38 patients on a standard immunosuppressive regimen, including cyclosporine, and matched them for age and serum creatinine. Endothelial cells were isolated from peripheral blood with anti-CD-146-coated immunomagnetic Dynabeads^TM and were counted by fluorescence microscopy. Patients with cyclosporine therapy had elevated numbers of circulating endothelial cells (median 26, range 12 to 82 cells/mL) compared with healthy controls (median 6, range 0 to 82 cells/mL; P<0.001). Patients without calcineurin inhibitor treatment had significantly lower cell numbers (median 12, range 0 to 32 cells/mL; P<0.003) and were not significantly different from normal, untreated controls. In conclusion, renal transplant recipients who do not receive calcineurin inhibitors have significantly lower numbers of circulating endothelial cells than their age- and creatinine-matched counterparts who receive these drugs. We suggest that elevated numbers of circulating endothelial cells indicate damage from calcineurin inhibitors in renal transplant recipients and that circulating endothelial cells are a novel marker of endothelial damage.

Key words: cyclosporine • endothelium • transplantation • vascular diseases

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