The true impact of DGF on kidney transplant outcomes remains debated, and in most studies, DGF is reported as a dichotomous outcome rather than a continuum. During this study period, we assessed 1714 DDKT of which, 59% (n = 1018) had DGF. We observed a median DGF duration of 10 days, with the majority of recipients (95%) showing resolution of DGF within 28 days. There were no differences in acute rejection events or interstitial fibrosis progression by 4 months when comparing DGF days. Readmissions increased with increasing DGF duration. Death-censored graft survival was not associated with the length of DGF except when DGF lasted > 28 days. To our knowledge, this is the first study to examine in detail the effect of DGF duration on rejection, readmissions, graft survival, and histology using a large cohort of deceased donor kidneys with DGF.
In a UK single center [7] study with DCD donors from 2011 to 2016, the presence of DGF was associated with lower graft survival, though the duration of DGF was not. In contrast, a UK registry-based DCD study [13] reported that DGF > 14 days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p = ·001) and recipient death (hazard ratio 1·8, p < 001) compared to grafts with immediate function [13]. That study reported a 2.5 times higher incidence of acute rejection within 3 months in recipients with DGF lasting > 14 days than those with DGF duration < 7 days. Because this was a registry-based study, there was insufficient data on induction and maintenance immunosuppression and if transplant centers held tacrolimus in the setting of DGF.
Authors Lim et al., using the Australian and New Zealand Dialysis and Transplant Registry, reported a direct effect between DGF duration and death-censored graft loss. [14] The authors reported DGF > 7 days was associated with a greater than 40% risk of graft loss. The Hazard Ratio for Death censored graft loss for DGF duration 8–13 days and > 14 days was 1.45 (1–2.1) and 1.6 (1.1–2.3) when compared to DGF duration 1–4 days. Suggesting, DGF duration > 7 days had a 45% higher relative risk for Death censored graft loss over the entire follow-up period.
The authors also reported an association between DGF duration and risk for acute rejection [1.17 (1.10–1.25; p < 0.001)]; subjects who developed acute rejection at 6 months were more likely to have graft loss [14]. Although this reported association is worrisome, it is important to note that the study had a higher incidence of acute rejection, 30% risk at 6 months, greater than expected. The lower use of T-cell depleting induction (3.5% with DGF vs. 10.7% without DGF) may have contributed to this finding [14]. In our present study, DGF days did not negatively impact death-censored graft survival except for those patients with DGF duration > 28 days. Duration of DGF also had no impact on acute rejection as compared to the registry-based studies mentioned above. By comparison, depleting agents were used in 70% of our recipients with DGF. By protocol, our center also does not modify induction or delay initiation of calcineurin inhibitors in the setting of DGF. Our center's practice of early tacrolimus initiation combined with higher levels (8–10 ng/ml) within the first month of the transplant could be reasons for these observed differences in early rejection.
There is controversy if an increase in Cold Ischemia Time and DCD kidneys is associated with an increased risk of BKV replication due to ischemia–reperfusion causing viral activation [21,22,23]. We did not find an association between DGF and BKV infection in this cohort.
Despite some data suggesting otherwise, there continue to be concerns in the transplant community regarding the impact of DGF on the progression of allograft interstitial fibrosis. We have previously demonstrated that DGF does not increase the risk for interstitial fibrosis at one year [19]. In the current study, we studied the effect of DGF duration on the risk of interstitial fibrosis progression. We did not find any significant impact of DGF days on the progression of chronic interstitial fibrosis compared to time 0 post-reperfusion biopsies to 4 months protocol.
Our center aims to discharge patients on post-transplant days 2–3 irrespective of DGF. As we have previously reported, our center's protocol is to routinely discharge patients with outpatient non-hospital based hemodialysis and close follow-up in our outpatient transplant clinic to minimize hospital length of stay. The median length of stay was 3 days, irrespective of DGF days. We observed higher readmission rates at 30 and 90 days, with increasing DGF duration. Compared to those without DGF, recipients with DGF lasting > 14 days had a 22–24% higher 30-day readmission rate and 27–30% higher 90-day readmission rate.
We also recognize that the need to start and continue dialysis is subjective. There can be variation regarding this decision within the center and between centers. Some centers may also be conservative with respect to dialyzing patients versus medical management. Since we have easy access to outpatient dialysis, it may result in less strict criteria for dialysis. Besides the center's practice of accepting more donors with severe AKI kidneys and long cold ischemia time, the different thresholds for dialysis may also play a role in higher DGF rates in our patient population.
Unlike previously published studies [13, 14], death-censored graft survival was not associated with the length of DGF except when DGF lasted > 28 days. Graft loss in patients with DGF lasting > 28 days was often due to a combination of donor and recipient factors. Recipient factors contributing to the graft loss identified in our study included cardiovascular complications, severe infections, acute rejection, and glomerulonephritis. For these recipients, prolonged DGF and associated outcomes appeared to be secondary to these post-transplant events.