Over the past 10 years, organizational and legal changes to the UK organ donation and transplantation frameworks have led to a significant increase in deceased donor organ transplantation, in general, and to kidney transplantation, in particular.1 The increase has occurred mainly through the greater use of organs from donation after circulatory death (DCD) donors and from donors older than 60 years.
Although DCD donors have been identified as a poor prognostic factor for renal allograft survival in some countries,2 UK analyses have shown equivalent long-term outcomes after kidney transplantation from DCD donors when compared with those from donation after brain death (DBD) donors.3,4 However, recipients of kidneys from donors aged 60 years or older have inferior transplant survival.5 Although these “marginal” donor kidneys may not be suitable for younger patients on the transplant waitlist, they may offer other potential recipients an opportunity to benefit from transplantation over remaining on the waitlist in the hope of receiving an organ with lower risk at a future date.6
It is essential that organ allocation and offering schemes consider the changing donor types and demographics. This is particularly relevant to DCD organ donation, because kidneys from these donors seem to have less tolerance to prolonged cold ischemic times (CITs) than kidneys from DBD donors3 and are therefore more susceptible to discard if an accepting center subsequently declines the organ once donation has occurred. The rise in the number of DCD donors and older donors is likely to have been at least partly responsible for increasing kidney discard rates in the UK between 2005 and 2011.7,8
The UK Kidney Fast-Track Scheme (KFTS) was introduced in 2012 after an analysis of discarded kidneys identified a high proportion that were potentially transplantable but had not been identified by the existing allocation pathway as kidneys at high risk of discard.7 Since then, deceased donor kidneys meeting defined entry criteria for the KFTS are simultaneously offered to all transplant centers that have opted to take part in the scheme. Kidneys are allocated per existing algorithms,9 but with the added flexibility that the accepting center can implant the kidney(s) into the recipient(s) of their choosing. National outcomes of kidneys implanted through the UK KFTS have not previously been reported.
Using the UK Transplant Registry, this analysis compares the characteristics of the donors and recipients transplanted with deceased donor kidneys offered through the KFTS with those offered via the standard National Kidney Allocation Scheme (NKAS) only. Short-term posttransplant outcomes of organs transplanted through these 2 offering pathways are presented. Finally, the effect of the KFTS on organ discard is examined.
MATERIALS AND METHODS
Organizational aspects of deceased donor kidney transplantation in the UK are described in detail elsewhere.7,9 Briefly, there are 24 adult kidney transplant centers, and kidney allocation varies per donor type (DBD or DCD) and has evolved during the study period. Kidneys from DBD donors are offered nationally, in accordance with the 2006 NKAS that allocates organs based on donor and recipient factors such as ABO blood group match, HLA mismatch, sensitization to HLA, waiting time, and donor-recipient age difference.9 Before September 2014, both kidneys from controlled DCD (Maastricht III and IV) donors were offered to the local transplant center. Since September 2014, 1 kidney from each DCD donor was offered to the local center, and 1 kidney was offered to a transplant unit within a designated UK region, prioritized per points calculated using the NKAS algorithm. Kidneys from DCD donors aged younger than 5 years or older than 50 years (65 years in the London region) were both allocated to the same center. Offering occurred sequentially, and each center was given up to 60 minutes to respond to each offer. Kidney procurement occurred only if an implanting center had accepted the offer.
The UK KFTS was introduced on November 1, 2012, for DBD donors and on March 1, 2013, for DCD donors. Kidneys were offered through the KFTS if any of the following criteria were met:
- 1) If, at any point, a procured kidney was deemed unusable by a donor coordinator or a member of the procuring or transplanting teams (excluding those kidneys with an absolute contraindication to transplantation).
- 2) If 5 centers declined a kidney offer for either donor- or organ-quality reasons. The reasons may differ between centers. Kidneys from DCD donors required 3 center declines for donor or organ quality.
- 3) If the kidney has accrued 6 hours of CIT and had not yet been accepted for transplantation (or 12 hours of CIT in the case of kidneys that are first accepted as part of a multiorgan transplant, eg, simultaneous pancreas-kidney transplant). Kidneys from DCD donors required 3 hours of CIT (or 6 hours if first accepted as part of a multiorgan transplant).
- 4) If a kidney from a Maastricht III DCD donor has been accepted for transplantation but was subsequently declined by the implanting center after withdrawal of life-sustaining treatment but before organ procurement had begun.
Transplant centers were invited to “opt in” to the KFTS, that is, to receive offers through the scheme. When one of the KFTS criteria was met, the organ was offered simultaneously to all participating centers. Offers were made electronically, through fax or mobile phone short message service text messaging. Centers had 45 minutes to respond; at the end of which, the kidney was allocated to the accepting center with the highest scoring patient (per the NKAS scoring algorithm). The accepting center can implant the kidney(s) into any recipient(s) on the center's waitlist that is blood group and HLA antibody compatible. In other words, the NKAS algorithm is used to determine which center gets the kidney through the KFTS but not which recipient gets the kidney within the accepting center. If the donor HLA type was not known at the time of the KFTS offer, it was not possible to use the NKAS algorithm, and therefore, the kidney was offered to the center that was first to accept. Figure 1 summarizes the KFTS pathway.
Data Collection and Definitions
The data were retrospectively obtained from the UK Transplant Registry on all potential and actual DBD kidney donors between November 1, 2012, and April 30, 2015, and all potential and actual Maastricht III and IV DCD kidney donors between March 1, 2013, and April 30, 2015. Recipients of kidney-only transplants from the said donors were followed up until October 19, 2016. Reasons for organ entry into the KFTS were not entered in the UK Transplant Registry, but the data on organ declines were collected.
DBD and DCD donors/transplants were considered separately, because criteria for entry into the KFTS differed. The standard DCD donor kidney allocation scheme has been described as “NKAS offering,” because the DCD allocation scheme changed during the study period, as previously described.
An en-bloc transplant was defined as a dual kidney transplant from a donor younger 18 years; a double transplant was defined as a dual kidney transplant from a donor aged 18 years or older. CIT was defined as the duration from time of cold perfusion in the donor to perfusion with the recipient's blood. Delayed graft function was defined as the need for dialysis within the first week of transplantation. Primary nonfunction (PNF) was defined as failure of a graft to ever function, regardless of the cause. Estimated glomerular filtration rates (eGFR) of functioning grafts were calculated using the 4-variable Modification of Diet in Renal Disease equation. Acute rejection was biopsy proven and occurred within the first 3 months after transplantation. Graft survival was defined as the time from transplantation until return to dialysis or graft nephrectomy, whichever was earlier, and was censored for patient death in some analyses. A discarded kidney was defined as an organ procured from a deceased donor for the purposes of transplantation but subsequently not implanted.
Kidney “quality” was quantified using the UK Kidney Donor Risk Index (UKKDRI),5 the expanded criteria donor (ECD) definition,10 and the Kidney Donor Profile Index (KDPI).2,11
χ2 tests were performed for categorical variables, and Kruskal-Wallis tests, for continuous variables to test for statistical differences between the groups. Kaplan-Meier survival curves were used to explore univariate differences in 1-year death-censored graft survival and 1-year patient survival. Survivals were compared using the log-rank test. Multivariable analysis of death-censored graft survival was performed using Cox proportional hazards modeling. All variables included in Table 1 were screened for inclusion in the Cox model; only those variables that were statistically significant (P < 0.05) were included in the final Cox model, after using a standard stepwise approach.
A 5% level of statistical significance was used throughout, and all analyses were performed using SAS Enterprise Guide (Version 6.1) with SAS 9.3 (SAS Institute Inc, Cary, NC).
Organ Offering and Utilization
Over the study period, 7839 kidneys from potential deceased donors were offered for kidney-only transplantation in the United Kingdom, with 1795 (23%) offered through the KFTS and 6044 (77%) offered through the NKAS only (Figure 2). Kidneys from DBD donors offered through the NKAS alone were far more likely to be procured than those offered through the KFTS (95% vs 64%, P < 0.001); once procured, these organs were also more likely to be transplanted (97% vs 62%, P < 0.001). A higher proportion of kidneys from potential DCD donors were procured if they were offered through the NKAS only (51% vs 40%, P < 0.001), although this difference was less marked than for DBD donors because many potential Maastricht III DCD donors do not proceed to circulatory arrest within the required period after treatment withdrawal. If kidney procurement occurred from a DCD donor, discard rates were far higher if organs were offered through the KFTS (45% vs 7%, P < 0.001).
Reasons for organs entering the KFTS were not recorded by the UK Transplant Registry, but analysis of offer decline data showed that most DBD donor kidneys entered the KFTS due to decline by 5 centers for reasons relating to the donor or the donor kidneys (303 [66%] of 457 donated kidneys and 185 [65%] of 286 transplanted kidneys). A lower proportion of DCD donor kidneys entered the KFTS because of multiple center declines (203 [47%] of 431 donated kidneys and 92 [39%] of 237 transplanted kidneys).
There was wide variation in the number of kidneys transplanted through the KFTS by the 12 centers participating in the scheme at the end of the study period (Figure 3A). To determine how enthusiastic each center was at using KFTS organs, the proportion of kidneys in each unit's deceased donor kidney transplant program that had come through the KFTS was compared (Figure 3B). This showed that most participating centers transplant 20% to 30% of their deceased donor kidneys through the KFTS. Only centers that opted in to the scheme at its initiation were included in this analysis, to ensure that the same periods were compared.
Donor, Organ, and Recipient Characteristics
As expected, donor characteristics of kidneys transplanted after offering through the KFTS were significantly different than those transplanted after offering through the NKAS alone (Table 1). KFTS kidneys were more likely to be from older, hypertensive, diabetic donors; kidneys from DBD donors implanted through the KFTS were more likely to be from donors with a noncerebrovascular accident cause of death, a history of drug abuse, and a past diagnosis of cancer. Donor risk indices reflected that KFTS organs were generally of higher risk, with higher proportion of ECDs, and higher median UKKDRI and KDPI scores. Suboptimal ex vivo cold flush quality was more frequent in transplanted KFTS kidneys, and CITs were longer.
Recipients of kidneys offered through the KFTS were older than recipients of NKAS-only kidneys, were on the waitlist for a shorter time, and had more HLA mismatches. Organs from DBD donors implanted through the KFTS were more likely to be given to first-time recipients, and those who were less sensitized. Double kidney transplants were less common in NKAS-only kidneys.
Early Posttransplant Outcomes
Outcomes of kidneys implanted after offering through the KFTS were compared with those that were transplanted through the NKAS alone. Organs transplanted into pediatric recipients (younger than 18 years) were excluded from all outcome analyses (ie, 119 and 11 recipients were excluded from the DBD and DCD NKAS groups, respectively). No KFTS kidneys were transplanted into pediatric recipients.
Kidneys transplanted after offering through the NKAS only were more likely to have immediate graft function than those transplanted after offering through the KFTS, although rates of PNF were similar (Table 2). Recipient eGFRs at 3 months and 12 months were statistically significantly higher in DBD donor kidneys transplanted through the NKAS-only pathway (49 vs 47 mL/min per 1.73 m2 [P = 0.001] and 52 vs 49 mL/min per m2 [P = 0.01], respectively). For DCD donor kidneys, there was no difference in 3- or 12-month recipient eGFRs between the 2 offering schemes (44 vs 43 mL/min per 1.73 m2 [P = 0.40] and 48 vs 45 mL/min per m2 [P = 0.10]). There was no difference in unadjusted 12-month death-censored graft survival for DBD donor kidney transplants from the 2 offering pathways (P = 0.70), although KFTS DCD donor kidneys had lower unadjusted 1-year graft survivals than NKAS-only DCD kidneys (P = 0.04) (Figure 4A). All cause graft survival (ie, including patient death with a functioning graft as graft failure) is shown in Figure S1, SDC,http://links.lww.com/TP/B462. There were no differences in patient survival for either DBD or DCD donor kidneys when comparing those organs transplanted through the KFTS versus those offered through the NKAS alone (Figure 4B).
One-year death-censored graft survival was adjusted for all the donor, organ, and recipient factors in Table 1 using a Cox proportional hazards model to determine if offering through the KFTS was independently associated with graft failure (Table 3). For both DBD and DCD donor kidneys, offering through the KFTS was not an independent predictor of graft survival.
Organ Discard Rates
The proportion of procured deceased donor kidneys that were discarded per year was examined before and after the introduction of the KFTS (Figure 5). Organ discard rates increased progressively from 2006 to 2012. Since 2013, it seems that discard rates have stabilized. Figures S2 and S3, SDC,http://links.lww.com/TP/B462 show discard rate by DBD/DCD donor type. Stabilization of discard rates cannot be readily explained by changes in donor selection criteria, because the donor risk of procured, implanted, and discarded organs has not changed appreciably from 2012 onward (Figure 6, and Figures S4, S5, S6, S7, and S8, SDC,http://links.lww.com/TP/B462).
This is the first national report on organs offered and transplanted through the new UK KFTS; previous work examined outcomes from kidneys transplanted at a single center only.8 This much larger analysis has shown that a high proportion of kidneys from deceased donors were offered through the KFTS. Kidneys transplanted through the KFTS were more likely to be from older, hypertensive donors and had higher UKKDRI scores and KDPIs. Most kidneys entered the KFTS because of multiple center declines. Recipients of these organs were more likely to be older than recipients of NKAS-only kidneys with more HLA mismatches. Despite less favorable donor and recipient characteristics (and longer CITs), KFTS kidneys had acceptable 1-year graft and patient outcomes. Longer follow-up may be needed to detect graft survival differences between KFTS and NKAS kidneys. However, these early findings should give confidence to centers and surgeons participating in the KFTS and may aid increased usage of organs offered through the scheme.
Kidneys offered through the KFTS have a much higher rate of discard than those kidneys offered through the NKAS. Since the introduction of the scheme, deceased donor kidney discard rates in the United Kingdom have remained steady. This implies that the KFTS entry criteria are successful at identifying organs at high risk of discard and that the scheme may have contributed to a stabilization of organ discard rates. However, it should be noted that kidney discard rates have not declined, and stable discard rates may also be due to static donor risk profiles. The authors feel that it is not feasible to calculate how many additional kidneys were implanted or discarded because of the introduction of the KFTS, because the KFTS was introduced at a national level, and therefore, any comparator groups are historical. Over the past 10 years, deceased donor characteristics in the United Kingdom have changed considerably, and therefore, historical control groups are unlikely to be relevant to current practice.
Discard rates are likely to be influenced by multiple other factors, including perceived donor risk profile,12,13 provision of donor risk scores at organ offering,14 time taken for organ transport, adequacy of access to theaters, organ assessment strategies (eg, widespread use of preimplantation biopsies15 or hypothermic machine perfusion16), surgeon experience, local outcomes of higher risk organs, and regulatory oversight of center outcomes.17 Despite the complexity and likely interaction of factors leading to organ discard, offering schemes can play a critical role in reducing the unnecessary discard of deceased donor kidneys. Such schemes should identify organs at high risk of discard and offer them to centers that are most likely to implant them.13,17 The UK KFTS seems to be achieving these aims.
The KFTS enables clinicians to use their judgment regarding the most suitable recipients for such organs because offers are not on a “named patient” basis, that is, once allocated to a center the kidney(s) can be implanted into any recipient on that center's waitlist. It is notable that recipients of KFTS kidneys were more likely to be older with shorter waiting times and less favorable HLA matching than recipients of kidneys offered through the NKAS only. Double kidney transplants of KFTS organs were also far more frequent. This is not surprising because KFTS kidneys are intrinsically more “marginal” than kidneys transplanted after offering through the NKAS alone. It seems that transplanting surgeons are being highly selective in their choice of recipient for KFTS kidneys and that HLA matching is less of a concern than the ability to implant these organs in a timely manner. The flexibility inherent in the KFTS is an important factor in minimizing CITs, enabling centers to select nonsensitized or minimally sensitized recipients who are suitable for transplantation without a prospective cross match.18 Centers have the freedom to choose recipients who require a prospective cross match, if they wish.
This approach is like that used by Eurotransplant, where “rescue allocation” occurs if a deceased donor kidney offer is declined for medical reasons by 5 different centers and the accepting center may choose the recipient from all compatible recipients on their list. An analysis of Eurotransplant kidneys in 2006 to 2007 showed that the rescue allocation pathway was used for 16% of donors, and approximately half of organs offered through the scheme were transplanted.19 These proportions are notably like those seen in the UK KFTS, and both the United Kingdom and Eurotransplant have kidney discard rates of 10% to 12%.20 The United States has a kidney discard rate of 18% to 20%15 and does not have an allocation or offering scheme aimed at identifying organs at high risk of discard.
It is likely that the UK KFTS will require modifications in future to continue to fulfill its aims. Firstly, current entry criteria were developed without a formal analysis of characteristics of discarded organs; the development of such scoring systems may enable more accurate identification of organs at high risk of discard.12,16 Secondly, the CIT thresholds within the KFTS entry criteria were designed to enable organs to be accepted, transported, and implanted with CITs of less than 24 or 12 hours for kidneys from DBD or DCD donors, respectively.3 However, for a subset of kidneys from younger donors, graft outcomes may still be acceptable even if CITs are prolonged. Offering these organs through the KFTS may not be appropriate because this may result in reduced access to transplantation for some patients. Careful analysis of outcomes of organs by KFTS entry criteria is therefore required once sufficient numbers accumulate. Thirdly, a recent study has suggested that usable kidneys are being discarded in the United Kingdom. Attaching images of declined organs to electronic KFTS offers may help reduce unnecessary organ discard.21 Finally, multiple center declines after offering through the NKAS may not be due to unacceptably risk-averse decisions; rather, this may reflect that the NKAS is inappropriately selecting potential recipients (eg, offering highly marginal elderly kidneys to young waitlist patients). Given the significant changes in UK deceased donor demographics over the past 10 years, a review of the NKAS is currently being undertaken to ensure that the predominant allocation pathway is still relevant.
The authors recognize the weaknesses of this article. Because the DBD and DCD schemes were introduced at different dates and had different entry criteria, outcomes of each were analyzed separately. In addition, the posttransplant follow-up period is short. Thus, confidence intervals on graft survival were relatively wide. It should also be noted that early outcome measures collected by registry analyses are not able to fully capture adverse events associated with some higher risk organs, for example, donor-transmitted diseases. The UK Transplant Registry did not capture fully the indications for organ entry into the KFTS, and therefore, it is difficult to analyze organ outcome by reason for entry into the scheme and to consider modifying the entry criteria, if needed. This has now been rectified and will enable the analysis discussed previously.
In summary, a significant proportion of UK deceased donor kidney offers now goes through the new fast-track scheme. These kidneys have a much higher rate of discard than those offered through the NKAS only, indicating that the scheme is efficiently identifying organs at increased risk of discard. Kidneys transplanted after offering through the KFTS were more likely to be from older, hypertensive, diabetic donors, with other unfavorable characteristics. CITs were longer, and recipients were older and less well matched for HLA. Notwithstanding these unfavorable characteristics, short-term posttransplant outcomes were acceptable, with 1-year unadjusted death-censored graft survival of more than 90%. Since the introduction of the KFTS, discard rates in the United Kingdom have stabilized, although reasons for this are likely to be multifactorial and complex. National schemes that identify and rapidly offer kidneys at high risk of discard may contribute to minimizing the unnecessary discard of organs. Countries without such schemes should consider their introduction.
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