title: Vasodilatation vs. immunotherapy to prevent delayed graft function: delayed graft function as an indication of immune activation.
abstract: Delayed renal allograft function (DGF) is a factor for acute rejection and chronic allograft nephropathy. Cold ischemia time (CIT) is associated with an increased in DGF. Twenty patients receiving allografts with CIT>12 were enrolled in a double-blinded, randomized (1:1), placebo-controlled study to assess vasodilatation with fenoldopam (Abbott; dopamine-1 receptor agonist) on DGF. Fenoldopam infusion began at arterial anastomosis at 0.025 microg/kg/min and titrated to 0.1 microg/kg/min continued for 48 h postop (PO). Immunosuppression included steriods, MMF, and calcinurin inhibitors begun 36 h PO. Antibody induction (AI) using antithymocyte globulin (rabbit) (AT-G(r); Sangstat) was added halfway through the study to African-Americans and for PRA>40%. The need for dialysis, cumulative urine output (UOP), and creatinine (Cr) at PO day 7, 14, and 30 were compared. Eighteen patients completed the study drug infusion. Demographics of groups were not different. There was no difference between fenoldopam and controls for dialysis, UOP at 48 and 72 h, or Cr at 7, 14, or 30 days. There was a difference in UOP when AI (n=7) was compared to non-AI (n=11). At 48 h non-AI UOP 4796+/-3284 ml compared to AI UOP 8960+/-5130 ml (p=0.050). At 72 h, non-AI patients had UOP of 6824+/-4547 ml compared to AI patients with UOP of 12196+/-5868 ml (p=0.044). There was a trend to a lower Cr at day 7 for AI 2.7+/-2.1mg/dl compared to 4.9+/-3.0 mg/dl in non-AI (p=0.11). There was no difference in dialysis or Cr at day 14 and 30 between the AI and non-AI patients. AI with AT-G(r) significantly increases UOP in allografts with CIT>12 h, whereas vasodilatation did not. Therapy for DGF may include AT-G(r) AI.
authors.affiliation: Renal Transplant Program, Sentara Norfolk General Hospital, Norfolk, VA, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: McCune
authors.forename: Duane G
authors.initials: DG
authors.lastname: Wombolt
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Whelan
authors.forename: Leroy R
authors.initials: LR
authors.lastname: Thacker
authors.forename: John O
authors.initials: JO
authors.lastname: Colonna
mesh_terms: D000328:Adult; D000917:Antibody Formation; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D018818:Fenoldopam / Q000627:therapeutic use*; D006084:Graft Rejection / Q000503:physiopathology / Q000628:therapy* / Q000652:urine; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014664:Vasodilation; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D014665:Vasodilator Agents; D003404:Creatinine; D018818:Fenoldopam