Elevated numbers of circulating endothelial cells in renal transplant recipients.
BACKGROUND
Damage of microvascular endothelial cells is a salient feature of acute vascular rejection and chronic allograft nephropathy, yet specific blood markers of ongoing endothelial injury are currently unavailable. Circulating endothelial cells have recently been established as a novel marker of endothelial damage in a variety of vascular disorders.


METHODS
We studied 129 renal transplant recipients who underwent percutaneous graft biopsy. Circulating endothelial cells were isolated with immunomagnetic anti-CD146-coated Dynabeads. Cells were stained with acridine and counted. To verify their endothelial origin, staining for Ulex europaeus lectin 1 (UEA-1) was performed in parallel. Twenty-one healthy controls were also studied.


RESULTS
On biopsy, seven patients had acute vascular rejection, 15 patients had acute tubulointerstitial rejection, 14 patients had borderline rejection, and 93 patients had no rejection. Patients with acute vascular rejection had the highest cell numbers (72+/-39 cells/mL) when compared with all other patients (P<0.02). Regardless of their biopsy findings, however, all other renal transplant recipients had significantly higher numbers of circulating endothelial cells (25+/-20 cells/mL) than healthy controls (7+/-5 cells/mL, P<0.001). Finally, there was a significant correlation of cell numbers and serum cyclosporine A trough levels. By contrast, there was no correlation with serum creatinine, age, or the number of immunosuppressive drugs.


CONCLUSIONS
The number of circulating endothelial cells is a novel marker of endothelial damage in renal transplant recipients. Further studies must now evaluate the origin of these cells, corroborate the clinical significance of our findings, and delineate the influence of calcineurin inhibitors.
Woywodt
Alexander
A
Department of Medicine, Hannover Medical School, Hannover, Germany. woywodt.alexander@ mh-hannover.de.
Schroeder
Maik
M
Gwinner
Wilfried
W
Mengel
Michael
M
Jaeger
Mark
M
Schwarz
Anke
A
Haller
Hermann
H
Haubitz
Marion
M
D000208:Acute Disease; D015703:Antigens, CD / Q000097:blood; D001706:Biopsy; D001773:Blood Cells / Q000473:pathology; D003404:Creatinine / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000473:pathology* / Q000652:urine; D006801:Humans; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011507:Proteinuria; D012079:Renal Circulation
D015703:Antigens, CD; D003404:Creatinine