Effects of dopamine donor pretreatment on graft survival after kidney transplantation: a randomized trial

Background and objectives: Donor dopamine improves initial graft function after kidney transplantation due to antioxidant properties. We investigated if a 4 µg/kg per minute continuous dopamine infusion administered after brain-death confirmation affects long-term graft survival and examined the exp...

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Main Authors: Schnülle, Peter (Author) , Schmitt, Wilhelm (Author) , Weiß, Christel (Author) , Zeier, Martin (Author) , Drüschler, Felix (Author)
Format: Article (Journal)
Language:English
Published: March 7, 2017
In: Clinical journal of the American Society of Nephrology
Year: 2017, Volume: 12, Issue: 3, Pages: 493-501
ISSN:1555-905X
DOI:10.2215/CJN.07600716
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.2215/CJN.07600716
Verlag, kostenfrei, Volltext: https://cjasn.asnjournals.org/content/12/3/493
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Author Notes:Peter Schnuelle, Wilhelm H. Schmitt, Christel Weiss, Antje Habicht, Lutz Renders, Martin Zeier, Felix Drüschler, Katharina Heller, Przemyslaw Pisarski, Bernhard Banas, Bernhard K. Krämer, Matthias Jung, Kai Lopau, Christoph J. Olbricht, Horst Weihprecht, Peter Schenker, Johan W. De Fijter, Benito A. Yard, and Urs Benck
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Summary:Background and objectives: Donor dopamine improves initial graft function after kidney transplantation due to antioxidant properties. We investigated if a 4 µg/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. Design, setting, participants, & measurements: 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.
Item Description:Gesehen am 22.08.2018
Published online March 7, 2017
Physical Description:Online Resource
ISSN:1555-905X
DOI:10.2215/CJN.07600716