title: Pretransplantation recipient regulatory T cell suppressive function predicts delayed and slow graft function after kidney transplantation.
abstract: BACKGROUND
  Delayed graft function (DGF) and slow graft function (SGF) are a continuous spectrum of ischemia-reperfusion-related acute kidney injury (AKI) that increases the risk for acute rejection and graft loss after kidney transplantation. Regulatory T cells (Tregs) are critical in transplant tolerance and attenuate murine AKI. In this prospective observational cohort study, we evaluated whether pretransplantation peripheral blood recipient Treg frequency and suppressive function are predictors of DGF and SGF after kidney transplantation.
  
  
  METHODS
  Deceased donor kidney transplant recipients (n=53) were divided into AKI (n=37; DGF, n=10; SGF, n=27) and immediate graft function (n=16) groups. Pretransplantation peripheral blood CD4CD25FoxP3 Treg frequency was quantified by flow cytometry. Regulatory T-cell suppressive function was measured by suppression of autologous effector T-cell proliferation by Treg in co-culture.
  
  
  RESULTS
  Pretransplantation Treg suppressive function, but not frequency, was decreased in AKI recipients (P<0.01). In univariate and multivariate analyses accounting for the effects of cold ischemic time and donor age, Treg suppressive function discriminated DGF from immediate graft function recipients in multinomial logistic regression (odds ratio, 0.77; P<0.01), accurately predicted AKI in receiver operating characteristic curve (area under the curve, 0.82; P<0.01), and predicted 14-day estimated glomerular filtration rate in linear regression (P<0.01).
  
  
  CONCLUSIONS
  Our results indicate that recipient peripheral blood Treg suppressive function is a potential independent pretransplantation predictor of DGF and SGF.
authors.affiliation: 1 Multi-Organ Transplant Program, McGill University Health Centre, McGill University, Montreal, Quebec, Canada. 2 Division of General Surgery, Department of Surgery, McGill University Health Centre, McGill University, Montreal, Quebec, Canada. 3 Department of Pathology, Duff Medical Sciences Building, McGill University, Montreal, Quebec, Canada. 4 Division of Nephrology, Department of Medicine, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. 5 Division of Nephrology, Department of Medicine, McGill University Health Centre, McGill University, Montreal, Quebec, Canada. 6 Address correspondence to: Steven Paraskevas, M.D., Ph.D., McGill University Health Centre (Royal Victoria Hospital), 687 Pine Ave West, Montreal, Quebec, Canada, H3A 1A1.
authors.forename: Minh-Tri J P
authors.initials: MT
authors.lastname: Nguyen
authors.forename: Elise
authors.initials: E
authors.lastname: Fryml
authors.forename: Sossy K
authors.initials: SK
authors.lastname: Sahakian
authors.forename: Shuqing
authors.initials: S
authors.lastname: Liu
authors.forename: Rene P
authors.initials: RP
authors.lastname: Michel
authors.forename: Mark L
authors.initials: ML
authors.lastname: Lipman
authors.forename: Istvan
authors.initials: I
authors.lastname: Mucsi
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cantarovich
authors.forename: Jean I
authors.initials: JI
authors.lastname: Tchervenkov
authors.forename: Steven
authors.initials: S
authors.lastname: Paraskevas
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D051799:Delayed Graft Function / Q000276:immunology*; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011446:Prospective Studies; D012044:Regression Analysis; D051437:Renal Insufficiency / Q000150:complications / Q000601:surgery; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit