title: Circulating endothelial progenitor cells in kidney transplant patients.
abstract: BACKGROUND
  Kidney transplantation (RTx) leads to amelioration of endothelial function in patients with advanced renal failure. Endothelial progenitor cells (EPCs) may play a key role in this repair process. The aim of this study was to determine the impact of RTx and immunosuppressive therapy on the number of circulating EPCs.
  
  
  METHODS
  We analyzed 52 RTx patients (58±13 years; 33 males, mean ± SD) and 16 age- and gender-matched subjects with normal kidney function (57±17; 10 males). RTx patients received a calcineurin inhibitor (CNI)-based (65%) or a CNI-free therapy (35%) and steroids. EPC number was determined by double positive staining for CD133/VEGFR2 and CD34/VEGFR2 by flow cytometry. Stromal cell-derived factor 1 alpha (SDF-1) levels were assessed by ELISA. Experimentally, to dissociate the impact of RTx from the impact of immunosuppressants, we used the 5/6 nephrectomy model. The animals were treated with a CNI-based or a CNI-free therapy, and EPCs (Sca+cKit+) and CD26+ cells were determined by flow cytometry.
  
  
  RESULTS
  Compared to controls, circulating number of CD34+/VEGFR2+ and CD133+/VEGFR2+ EPCs increased in RTx patients. There were no correlations between EPC levels and statin, erythropoietin or use of renin angiotensin system blockers in our study. Indeed, multivariate analysis showed that SDF-1--a cytokine responsible for EPC mobilization--is independently associated with the EPC number. 5/6 rats presented decreased EPC counts in comparison to control animals. Immunosuppressive therapy was able to restore normal EPC values in 5/6 rats. These effects on EPC number were associated with reduced number of CD26+ cells, which might be related to consequent accumulation of SDF-1.
  
  
  CONCLUSIONS
  We conclude that kidney transplantation and its associated use of immunosuppressive drugs increases the number of circulating EPCs via the manipulation of the CD26/SDF-1 axis. Increased EPC count may be associated to endothelial repair and function in these patients.
authors.affiliation: Medizinische Klinik und Poliklinik D, Universitätsklinikum Münster, Münster, Germany.
authors.forename: Giovana S
authors.initials: GS
authors.lastname: Di Marco
authors.forename: Peter
authors.initials: P
authors.lastname: Rustemeyer
authors.forename: Marcus
authors.initials: M
authors.lastname: Brand
authors.forename: Raphael
authors.initials: R
authors.lastname: Koch
authors.forename: Dominik
authors.initials: D
authors.lastname: Kentrup
authors.forename: Alexander
authors.initials: A
authors.lastname: Grabner
authors.forename: Burkhard
authors.initials: B
authors.lastname: Greve
authors.forename: Werner
authors.initials: W
authors.lastname: Wittkowski
authors.forename: Hermann
authors.initials: H
authors.lastname: Pavenstädt
authors.forename: Martin
authors.initials: M
authors.lastname: Hausberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Reuter
authors.forename: Detlef
authors.initials: D
authors.lastname: Lang
mesh_terms: D000818:Animals; D065095:Calcineurin Inhibitors; D002452:Cell Count; D042783:Endothelial Cells / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects
chemical_list: D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents