Prolonged duration of delayed graft function (DGF) may be associated with adverse allograft outcomes, but the association between threshold duration of DGF, acute rejection and long-term allograft loss remains undefined. We aimed to determine the impact of DGF duration on allograft outcomes and to assess whether this association was mediated by acute rejection.
Using data from the Australian and New Zealand Dialysis and Transplant Registry, Cox proportional modeling was used to determine the association between quartiles of DGF duration, acute rejection at 6 months and death-censored graft loss (DCGL). Mediation analysis was conducted to determine whether acute rejection was a causal intermediate between DGF and DCGL.
Of 7668 deceased donor kidney transplants between 1997 and 2014, 1497 (19.5%) recipients experienced DGF requiring dialysis. The median (interquartile range) duration of DGF was 7 (9) days, with 25% requiring dialysis for 14 days or longer. Among recipients who had experienced a DGF duration of 1 to 4 days, the adjusted hazard ratio for duration of 5 to 7, 8 to 13, and 14 days or longer were 1.13 (95% confidence interval [CI], 0.83-1.55; P = 0.43), 1.44 (95% CI, 1.08-1.91; P = 0.013), and 1.99 (95% CI, 1.50-2.65; P < 0.001), respectively, for acute rejection; and were 1.10 (95% CI< 0.73-1.67; P = 0.64), 1.45 (95% CI, 1.00-2.11; P = 0.05) and 1.60 (95% CI, 1.10-2.31; P = 0.01), respectively, for DCGL. On average, 8% of the effects between DGF duration and DCGL were explained by acute rejection.
There was a direct dose-dependent effect between DGF duration and DCGL, with acute rejection explaining less than 10% of the effects between DGF duration and DCGL. Future research identifying other potential modifiable mediators that lies in the causal pathway between DGF duration and allograft loss is essential.
This study shows that there is a direct dose-dependent effect between the duration of delayed graft function and death-censored graft loss (DCGL). Surprisingly acute rejection explains <10% of the impact of delayed graft function duration and DCGL.
1 Department of Renal Medicine, Sir Charles Gairdner Hospital, Western Australia, Australia.
2 School of Medicine, University of Western Australia, Perth, Australia.
3 Australia and New Zealand Dialysis and Transplant Registry, Adelaide, Australia.
4 Princess Alexandra Hospital, Metro South and Ipswich Nephrology and Transplant Services, Queensland, Australia.
5 University of Queensland, Queensland, Australia.
6 Translational Research Institute, Brisbane, Australia.
7 Sydney School of Public Health, University of Sydney, Sydney, Australia.
8 Centre for Transplant and Renal Research, Westmead Hospital, Sydney, Australia.
9 Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia.
Received 20 January 2018. Revision received 1 April 2018.
Accepted 7 May 2018.
Wai H. Lim is supported by a Clinical Research Fellowship from the Raine Foundation, University of Western Australia and Health Department of Western Australia. David Johnson is supported by a National Health and Medical Research Council Practitioner Fellowship. Germaine Wong is supported by a National Health and Medical Research Council Career Development Fellowship.
The authors declare no conflicts of interest.
W.H.L. and G.W. participated in the research design and writing of the article. W.H.L., A.T.-P., and G.W. participated in the analysis of data. All other authors participated in the writing of the article.
Correspondence: Wai H Lim, PhD, Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia 6009, Australia. (firstname.lastname@example.org).
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