Association Between Duration of Delayed Graft Function, Acute Rejection, and Allograft Outcome After Deceased Donor Kidney Transplantation
- 1 February 2019
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Transplantation
- Vol. 103 (2), 412-419
- https://doi.org/10.1097/tp.0000000000002275
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.Keywords
This publication has 21 references indexed in Scilit:
- Is Delayed Graft Function Causally Associated With Long-Term Outcomes After Kidney Transplantation? Instrumental Variable AnalysisTransplantation, 2013
- Delayed Graft Function in the Kidney TransplantAmerican Journal of Transplantation, 2011
- A Risk Prediction Model for Delayed Graft Function in the Current Era of Deceased Donor Renal TransplantationAmerican Journal of Transplantation, 2010
- A General Model for Testing Mediation and Moderation EffectsPrevention Science, 2008
- Association between delayed graft function and allograft and patient survival: a systematic review and meta-analysisNephrology Dialysis Transplantation, 2008
- The influence of delayed graft functionNephrology Dialysis Transplantation, 2004
- Risk factors for delayed graft function after renal transplantation and their significance for long-term clinical outcomeTransplant International, 2002
- Risk factors for delayed graft function after renal transplantation and their significance for long-term clinical outcomeTransplant International, 2002
- Delayed graft function of more than six days strongly decreases long-term survival of transplanted kidneysKidney International, 1998
- DELAYED GRAFT FUNCTION IN THE ABSENCE OF REJECTION HAS NO LONG-TERM IMPACTTransplantation, 1996