title: Increased soluble Flt-1 correlates with delayed graft function and early loss of peritubular capillaries in the kidney graft.
abstract: BACKGROUND
  Ischemia-reperfusion induces tubular and endothelial damage in the renal graft and leads to delayed graft function (DGF) and to an early loss of peritubular capillaries (PTC). Few, if any, clinical studies have assessed the impact of proangiogenic and antiangiogenic factors on endothelial repair during renal transplantation (RT)-related ischemia-reperfusion.
  
  
  METHODS
  We prospectively assessed the kinetics of the antiangiogenic factor soluble Fms-like tyrosine kinase-1 (sFlt-1) in 136 consecutive RT patients and analyzed sFlt-1 impact on DGF and PTC loss.
  
  
  RESULTS
  sFlt-1 plasma levels increased by twofold to threefold throughout the first week after RT. This increase was more marked in recipients of grafts from deceased donors compared with living donors. Patients with DGF had higher sFlt-1 levels at all time points during the first 7 days after RT and a higher peak sFlt-1 compared with those without DGF. In multivariate analysis, a peak plasma sFlt-1 of 250 pg/mL or higher was associated with 2.5-fold increase in the risk of DGF (P=0.04). Similarly, patients with a peak plasma sFlt-1 of 250 pg/mL or higher had a more pronounced early decrease in PTC compared with those with a peak sFlt-1 less than 250 pg/mL.
  
  
  CONCLUSIONS
  sFlt-1 is a new nonimmunologic independent risk factor for DGF and PTC loss. Its inhibition may help improve the outcome of RT.
authors.affiliation: 1 ITUN, Department of Nephrology and Immunology, INSERM UMR S-1064, Nantes, France. 2 SPHERE (Biostatistics, Pharmacoepidemiology and Human Sciences Research) Laboratory-EA 4275, LabEx Transplantex, Nantes University, Nantes, France. 3 Department of Pathology, CHU de Nantes, Nantes, France. 4 Address correspondence to: Fadi Fakhouri, M.D., Ph.D., INSERM U643, ITUN, Université de Nantes and Nephrology Department CHU de Nantes, Nantes, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Chapal
authors.forename: Mélanie
authors.initials: M
authors.lastname: Néel
authors.forename: Florent
authors.initials: F
authors.lastname: Le Borgne
authors.forename: Emanuelle
authors.initials: E
authors.lastname: Meffray
authors.forename: Odette
authors.initials: O
authors.lastname: Carceles
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Hourmant
authors.forename: Magalie
authors.initials: M
authors.lastname: Giral
authors.forename: Yohann
authors.initials: Y
authors.lastname: Foucher
authors.forename: Anne
authors.initials: A
authors.lastname: Moreau
authors.forename: Fadi
authors.initials: F
authors.lastname: Fakhouri
mesh_terms: D000328:Adult; D000368:Aged; D002196:Capillaries / Q000473:pathology; D051799:Delayed Graft Function / Q000097:blood* / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000706:statistics & numerical data*; D007684:Kidney Tubules / Q000098:blood supply / Q000473:pathology; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D011183:Postoperative Complications / Q000097:blood* / Q000453:epidemiology* / Q000473:pathology; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000097:blood / Q000453:epidemiology / Q000473:pathology; D012307:Risk Factors; D012995:Solubility; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1