Association between Duration of Delayed Graft Function, Acute Rejection, and Allograft Outcome after Deceased Donor Kidney Transplantation

Wai H. Lim, David W. Johnson, Armando Teixeira-Pinto, Germaine Wong

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Original languageEnglish
Pages (from-to)412-419
Number of pages8
JournalTransplantation
Volume103
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019

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Delayed Graft Function
Kidney Transplantation
Allografts
Transplants
Confidence Intervals
Dialysis
New Zealand
Registries

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Lim, Wai H. ; Johnson, David W. ; Teixeira-Pinto, Armando ; Wong, Germaine. / Association between Duration of Delayed Graft Function, Acute Rejection, and Allograft Outcome after Deceased Donor Kidney Transplantation. In: Transplantation. 2019 ; Vol. 103, No. 2. pp. 412-419.
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title = "Association between Duration of Delayed Graft Function, Acute Rejection, and Allograft Outcome after Deceased Donor Kidney Transplantation",
abstract = "Background 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. Methods 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. Results 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. Conclusions 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.",
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Association between Duration of Delayed Graft Function, Acute Rejection, and Allograft Outcome after Deceased Donor Kidney Transplantation. / Lim, Wai H.; Johnson, David W.; Teixeira-Pinto, Armando; Wong, Germaine.

In: Transplantation, Vol. 103, No. 2, 01.02.2019, p. 412-419.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association between Duration of Delayed Graft Function, Acute Rejection, and Allograft Outcome after Deceased Donor Kidney Transplantation

AU - Lim, Wai H.

AU - Johnson, David W.

AU - Teixeira-Pinto, Armando

AU - Wong, Germaine

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Background 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. Methods 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. Results 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. Conclusions 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.

AB - Background 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. Methods 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. Results 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. Conclusions 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.

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U2 - 10.1097/TP.0000000000002275

DO - 10.1097/TP.0000000000002275

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