title: Effects of Dopamine Donor Pretreatment on Graft Survival after Kidney Transplantation: A Randomized Trial.
abstract: OBJECTIVE
  Donor dopamine improves initial graft function after kidney transplantation due to antioxidant properties. We investigated if a 4µg/kg per minute continuous dopamine infusion administered after brain-death confirmation affects long-term graft survival and examined the exposure-response relationship with treatment duration.
  
  
  METHODS
  Five-year follow-up of 487 renal transplant patients from 60 European centers who had participated in the randomized, multicenter trial of dopamine donor pretreatment between 2004 and 2007 (ClinicalTrials.gov identifier: NCT00115115).
  
  
  RESULTS
  Follow-up was complete in 99.2%. Graft survival was 72.6% versus 68.7% (P=0.34), and 83.3% versus 80.4% (P=0.42) after death-censoring in treatment and control arms according to trial assignment. Although infusion times varied substantially in the treatment arm (range 0-32.2 hours), duration of the dopamine infusion and all-cause graft failure exhibited an exposure-response relationship (hazard ratio, 0.96; 95% confidence interval [95% CI], 0.92 to 1.00, per hour). Cumulative frequency curves of graft survival and exposure time of the dopamine infusion indicated a maximum response rate at 7.10 hours (95% CI, 6.99 to 7.21), which almost coincided with the optimum infusion time for improvement of early graft function (7.05 hours; 95% CI, 6.92 to 7.18). Taking infusion time of 7.1 hours as threshold in subsequent graft survival analyses indicated a relevant benefit: Overall, 81.5% versus 68.5%;P=0.03; and 90.3% versus 80.2%;P=0.04 after death-censoring.
  
  
  CONCLUSIONS
  We failed to show a significant graft survival advantage on intention-to-treat. Dopamine infusion time was very short in a considerable number of donors assigned to treatment. Our finding of a significant, nonlinear exposure-response relationship disclosed a threshold value of the dopamine infusion time that may improve long-term kidney graft survival.
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material .
authors.forename: Peter
authors.initials: P
authors.lastname: Schnuelle
authors.forename: Wilhelm H
authors.initials: WH
authors.lastname: Schmitt
authors.forename: Christel
authors.initials: C
authors.lastname: Weiss
authors.forename: Antje
authors.initials: A
authors.lastname: Habicht
authors.forename: Lutz
authors.initials: L
authors.lastname: Renders
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.forename: Felix
authors.initials: F
authors.lastname: Drüschler
authors.forename: Katharina
authors.initials: K
authors.lastname: Heller
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Pisarski
authors.forename: Bernhard
authors.initials: B
authors.lastname: Banas
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
authors.forename: Matthias
authors.initials: M
authors.lastname: Jung
authors.forename: Kai
authors.initials: K
authors.lastname: Lopau
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Olbricht
authors.forename: Horst
authors.initials: H
authors.lastname: Weihprecht
authors.forename: Peter
authors.initials: P
authors.lastname: Schenker
authors.forename: Johan W
authors.initials: JW
authors.lastname: De Fijter
authors.forename: Benito A
authors.initials: BA
authors.lastname: Yard
authors.forename: Urs
authors.initials: U
authors.lastname: Benck
mesh_terms: D000328:Adult; D000368:Aged; D001926:Brain Death; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004298:Dopamine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006801:Humans; D057194:Intention to Treat Analysis; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011292:Premedication; D011300:Preoperative Care; D013997:Time Factors; D014019:Tissue Donors; D019737:Transplants / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D004298:Dopamine
keywords: arm; brain; brain death; brain-dead donor; cadaver organ transplantation; confidence intervals; death; donor pretreatment; dopamine; follow-up studies; graft survival; humans; intention to treat analysis; ischemia-reperfusion; kidney transplantation; outcomes; renal protection; renal transplantation; survival analysis; tissue donors; transplants