title: Association of graft neutrophil sequestration with delayed graft function in clinical renal transplantation.
abstract: BACKGROUND
  The authors studied the impact of neutrophil activation, detected in experimental models, on reperfusion injury in clinical renal transplantation.
  
  
  METHODS
  Forty-five patients from a larger trial comparing three immunosuppressive protocols were recruited: perioperative antithymocyte globulin (ATG) with low initial cyclosporine A (CsA) triple therapy (group A, n=15); two-dose basiliximab with low initial CsA triple therapy (group B, n=16); and conventional triple therapy (group C, n=14). Blood samples were obtained preoperatively, before reperfusion, and at 1 and 5 min after reperfusion. During reperfusion, samples were collected from the iliac artery and the graft vein for calculation of transrenal differences (Delta) of study parameters. Leukocyte differential counts, plasma lactoferrin concentration, and neutrophil CD11b and L-selectin expressions were assessed. Graft blood flow was measured at 2 and 30 min after reperfusion.
  
  
  RESULTS
  ATG induced neutrophil activation already before reperfusion. Thus, group A was excluded, but groups B and C were pooled for analysis of reperfusion-induced neutrophil activation. At 1 min after reperfusion, lactoferrin concentration was higher in graft vein than iliac artery, yielding Delta=15 microg/L (P<0.05). Concomitantly, Delta neutrophil count correlated with both Delta L-selectin expression (R=0.49, P=0.012) and graft blood flow at 2 min (R=0.51, P=0.007). At 5 min after reperfusion, 0.17 (-1.0-0.24)x10 cells/L neutrophils were sequestered in the graft (P<0.001). This sequestration correlated with graft blood flow at 30 min (R=0.53, P=0.005) and was stronger in patients with delayed graft function (DGF) (Delta = -0.38 [-1.45 to -0.2]) than those without (Delta = -0.12 [-0.41-0.24], P<0.001). In multiple regression analysis, sequestration was the most important parameter associated with DGF.
  
  
  CONCLUSIONS
  Neutrophils are activated and sequestered in the reperfused graft during clinical renal transplantation. Neutrophil sequestration is a powerful independent factor explaining the incidence of DGF.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Hospital, Haartmanninkatu 4, 00029 HUS Helsinki, Finland.
authors.forename: Arto J
authors.initials: AJ
authors.lastname: Turunen
authors.forename: Leena
authors.initials: L
authors.lastname: Lindgren
authors.forename: Kaija T
authors.initials: KT
authors.lastname: Salmela
authors.forename: Lauri E
authors.initials: LE
authors.lastname: Kyllönen
authors.forename: Heikki
authors.initials: H
authors.lastname: Mäkisalo
authors.forename: Sanna M
authors.initials: SM
authors.lastname: Siitonen
authors.forename: Eero J
authors.initials: EJ
authors.lastname: Pesonen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000502:physiology*; D007958:Leukocyte Count; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D015424:Reperfusion; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents