Delayed Graft Function is Correlated with Graft Loss in Recipients of Expanded-Criteria Rather Than Standard-Criteria Donor Kidneys: A Retrospective, Multicenter, Observation Cohort Study
Kidney transplantation remains the most cost-effective therapy for end-stage renal disease (ESRD). However, the growing disparity between the number of patients on the transplant waiting list and the availability of donor organs has led to the increased use of expanded-criteria donor (ECD) kidneys. While ECD kidneys help alleviate organ shortages, they are associated with a higher incidence of delayed graft function (DGF), a common complication post-transplantation. The impact of DGF on graft survival, however, remains uncertain. This study aimed to investigate the relationship between DGF and allograft survival, particularly in recipients of ECD versus standard-criteria donor (SCD) kidneys.
The study was conducted as a retrospective, multicenter, observational cohort analysis, involving 284 deceased donors and 541 kidney transplant recipients between February 2012 and March 2017. The primary outcome was DGF, defined as the need for dialysis within the first week post-transplantation. Graft loss was defined as the return to dialysis post-transplantation, excluding patients who died with a functioning graft. ECD kidneys were defined as those from donors aged 60 years or older, or donors aged 50 years or older with at least two of the following conditions: a history of hypertension, serum creatinine levels exceeding 1.5 mg/dL, or death due to cerebrovascular causes.
Among the 284 deceased donors, 65 (22.8%) were classified as ECD. Of the 541 recipients, 107 (19.8%) developed DGF. The incidence of DGF was significantly higher in recipients of ECD kidneys (29.2%) compared to SCD kidneys (17.1%). The 5-year graft survival rate did not differ significantly between SCD kidney recipients with and without DGF (95.8% vs. 95.4%). However, for ECD kidney recipients, those with DGF had a significantly lower 5-year graft survival rate (71.4%) compared to those without DGF (97.6%). Multivariate analysis revealed that DGF was an independent risk factor for graft loss in ECD kidney recipients, with an adjusted hazard ratio (HR) of 1.885. Induction therapy with anti-thymocyte globulin (ATG) was identified as a protective factor against DGF, with an odds ratio (OR) of 0.359, and a protective factor for graft survival in ECD kidney recipients, with an HR of 0.308.
The study highlighted several key findings. First, DGF is an independent risk factor for graft survival in recipients of ECD kidneys but not in recipients of SCD kidneys. This finding helps reconcile conflicting results in the literature regarding the impact of DGF on graft survival. Second, warm ischemia time (WIT) exceeding 18 minutes was associated with a higher incidence of DGF and graft loss. Recipients of ECD kidneys with WIT >18 minutes had a DGF rate of 47% and a graft loss rate of 16.4% over 5 years, compared to 13.8% and 4.6%, respectively, in recipients of ECD kidneys with WIT ≤18 minutes. This underscores the importance of minimizing WIT to improve outcomes in ECD kidney transplantation.
Third, induction therapy with ATG was shown to reduce the incidence of DGF and improve graft survival. Recipients of ECD kidneys who received ATG had a DGF rate of 22% and a graft loss rate of 7.5%, compared to 44% and 18.5%, respectively, in those who received basiliximab. This suggests that ATG is a superior induction therapy option for recipients of ECD kidneys.
The study also explored the relationship between donor proteinuria levels and graft outcomes. Donors with higher proteinuria levels (3+) were associated with an increased risk of DGF and graft loss. Recipients of ECD kidneys with DGF had a higher proportion of donors with proteinuria levels of 3+ (20%) compared to other groups. These recipients also exhibited a significant decline in estimated glomerular filtration rate (eGFR) and an increased probability of de novo proteinuria during the 5-year follow-up, further emphasizing the detrimental impact of DGF on long-term graft function.
The etiology of DGF in ECD kidneys was hypothesized to involve greater sensitivity to ischemia-reperfusion injury, diminished self-repair capabilities, and a higher likelihood of chronic kidney disease (CKD) in donors. These factors contribute to the increased incidence of DGF and poorer graft survival in ECD kidney recipients. The study also highlighted the interconnectedness of acute kidney injury (AKI) and CKD, with AKI in donors with CKD leading to more severe injury and difficult recovery post-transplantation.
In conclusion, this study provides critical insights into the factors influencing graft survival in kidney transplantation, particularly in the context of ECD kidneys. DGF was identified as an independent risk factor for graft loss in ECD kidney recipients, but not in SCD kidney recipients. Minimizing WIT and using ATG as induction therapy were shown to improve outcomes in ECD kidney transplantation. These findings have important implications for optimizing the use of ECD kidneys and improving long-term graft survival. Future research should focus on validating these results and exploring additional strategies to mitigate the risks associated with DGF in ECD kidney transplantation.
doi.org/10.1097/CM9.0000000000000666
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