title: Effect of conversion from ciclosporin to tacrolimus on endothelial progenitor cells in stable long-term kidney transplant recipients.
abstract: BACKGROUND
  Endothelial progenitor cell (EPC) counts are proposed surrogate markers for vascular function and cardiovascular risk. The effect of tacrolimus (TAC) on EPC is unknown.
  
  
  METHODS
  In this randomized controlled trial, we assigned 148 stable long-term kidney transplant recipients (KTR) to maintaining ciclosporin (CSA) or to commencing TAC-based immunosuppression at a 2:1 ratio. EPC counts (CD34/KDR) after 24 months were defined as primary endpoint.
  
  
  RESULTS
  The intent-to-treat analysis included 141 KTR (estimated glomerular filtration rate, 46.7 [40.1-61.8] mL/min per 1.73 m). Median (interquartile range [IQR]) EPC counts at baseline and month 24 were 6 (2-9) and 3 (1-9) cells and 4 (2-8) and 2 (0-5) cells per 5×10 mononuclear cells in CSA and TAC, respectively. Median (IQR) circulating angiogenic cells at baseline and month 24 were 28 (10.7-57) and 44.33 (14.6-59.8) cells and 22 (10.8-41) and 21 (9.7-49.5) cells per high-power field in CSA and TAC, respectively. Median (IQR) endothelial cell colony-forming units count per well at baseline and month 24 were 10.5 (3.3-34.3) and 4.38 (1.7-26.5) in CSA and significantly declined from 9.31 (1.8-29.3) to 4.13 (1.1-9.5) in TAC (P=0.003). There were no cardiovascular events in either group.
  
  
  CONCLUSIONS
  Although late conversion from CSA to TAC appears safe in KTR, conversion to TAC has no favorable effect on EPC. Low EPC levels are associated with a higher risk of subsequent cardiovascular events and are therefore of prognostic value. Their trend to decline over time deserves further examination.
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Riegersperger
authors.forename: Max
authors.initials: M
authors.lastname: Plischke
authors.forename: Sabine
authors.initials: S
authors.lastname: Steiner
authors.forename: Daniela
authors.initials: D
authors.lastname: Seidinger
authors.forename: Guerkan
authors.initials: G
authors.lastname: Sengoelge
authors.forename: Wolfgang C
authors.initials: WC
authors.lastname: Winkelmayer
authors.forename: Gere
authors.initials: G
authors.lastname: Sunder-Plassmann
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology; D002452:Cell Count; D016572:Cyclosporine / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D013234:Stem Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D016559:Tacrolimus / Q000494:pharmacology*; D014180:Transplantation
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus