Kidney transplantation due to medical urgency: time for reconsideration? Free

Patients with end-stage renal disease (ESRD) can survive if treated by either dialysis or transplantation. Although transplantation is the preferred modality for the majority of patients, not all have living donors and there is a significant disparity between organ demand and supply. Consequently, most patients listed for a deceased donor transplant wait for a long time on the list; in addition, the number of the patients awaiting transplants is on the rise [1]. The process of organ allocation is quite complex, balancing the concepts of efficiency, morality, community preferences, transparency and trust; hence, objective and fair decisions have to be made to allocate these already scarce organs.

Owing to extraordinary circumstances, a small number of patients might need to be transplanted urgently in order to survive, though these patients usually have multiple comorbidities and have the greatest risk of death with a functioning graft posttransplant. However, adoption of a strategy allocating some deceased donor kidneys to patients with medical urgency [high urgent (HU) transplantation] could disadvantage patients on the regular waiting list with the greatest life expectancy, especially in an era of trying to match the best kidneys for the best candidates in order to improve outcomes after transplantation.

Unfortunately, indications for HU transplantation are not well described, but rather differ significantly among countries around the globe. For example, there are no set rules on indication for HU listing in the USA. According to Organ Procurement and Transplant Network (OPTN) policy, prior to receiving an organ offer from a deceased donor in the same donation service area (DSA), a candidate's transplant physician may use medical judgement to transplant a patient out of sequence due to medical urgency. If there is more than one kidney transplant programme in the DSA, then the candidate's physician must contact the other transplant programmes and the organ procurement organizations in the area, explain the patient's condition and must receive agreement from the other transplant programmes to allocate the kidney out of sequence [2]. In the UK allocation system, priority listing has been clearly defined, especially for paediatric patients [3]; e.g. a child may be priority-listed regardless of match grade, in the event of potential imminent or actual loss of dialysis access or when dialysis access is likely to become difficult within a short period, and also when special restrictions are required for a suitable kidney (e.g. size due to anatomical difficulties in the recipient), which significantly restricts the possibility of an appropriate donor. It has been emphasized that before a child is priority-listed an independent review should be carried out by two clinicians from different transplant centres from where the child is listed [3]. According to the Transplantation Society of Australia and New Zealand, urgent listing has been indicated for patients who have a very high risk of death if they are not transplanted in the near future (e.g. patients with renal failure, who no longer have dialysis access). Patients on the urgent listing are offered the next compatible donor organ arising anywhere in these countries [4].

In the Eurotransplant (ET) Program, criteria for HU listing include imminent lack of access for either haemodialysis and/or peritoneal dialysis, severe (uraemic) polyneuropathy, inability to cope with dialysis with a high risk for suicide, and severe bladder problems such as haematuria or cystitis due to kidney graft failure after simultaneous kidney and pancreas transplantation [5]. Also, the HU status adds an extra 500 points for allocation, thus shortening the waiting time further for a small group of patients.

In reality, all these indications are not usually defined as ‘black and white’, but rather in tones of ‘grey’, subject to change. It is not clear what constitutes imminent lack of dialysis access, especially in an era where there have been significant changes to interventional radiology and the better options that they can offer to the patient who is considered to have poor dialysis access. Similar concerns exist on how to objectively define extreme depression or neuropathy that could necessitate an exception. Therefore, the above-mentioned indications for HU transplant are not standardized and reliable scientific data are lacking on this highly debatable practice.

In this issue of NDT Assfalg et al. [6] report the 5-year patient and graft outcomes of the HU kidney transplants performed between 1996 and 2010 at 61 ET centres and compare the results with transplants done using standard ET kidney allocation system (ETKAS) [5]. The data were obtained by sending a digital questionnaire to the transplant centres and reviewing the ET database and annual reports. Of the 937 HU transplant recipients (2.1% of all kidneys transplanted), 639 had complete data for evaluation. The authors focused on three subgroups: patients with lack of access (n = 500), ‘suicidality’ (n = 109) and neuropathy (n = 30). They found that patients transplanted due to HU had poorer patient survival and higher risk of death with a functioning graft compared with the general transplant population, despite being younger (median 43 years versus 55 years), whereas graft survival was comparable despite the higher number of HLA mismatches (mean 3.79 versus 2.42). HU transplant patients waited for shorter periods (34 versus 54 months) on the list. The most significant difference was in the largest, but likely the most heterogeneous, subgroup of patients with imminent lack of dialysis access; they had significantly lower patient survival compared with non-HU recipients and also HU recipients with ‘suicidality’. The authors speculated that HU recipients with access problems might have had worse cardiovascular status, although there were no actual data provided. On multivariable regression analysis, only re-transplantation was found to have a negative impact on graft survival in these patients. Another interesting finding was the significantly higher mortality on the standard waiting list compared with the HU waiting list (5.2 versus 0.7%, respectively).

There are a few other studies, though on a small number of patients with relatively short follow-up, published on the outcomes of HU transplants. Kleinert et al. [7] reported their experience in 10 patients who had the exhaustion of vascular access in combination with a bloodstream infection. All recipients had significant comorbidities such as cardiovascular disease combined with coronary artery disease, diabetes and chronic obstructive pulmonary disease, emphasizing the importance of additional information on comorbidities when evaluating these high-risk patients. Patient survival was 90% at 1, 80% at 3 and 60% at 5 years, much lower compared with their standard patients. In another study of 47 patients with imminent lack of dialysis access, patient survival was 90% at 1 year and 83% at 2 years (compared with 93% at 1 year and 84% at 2 years in the control group, P = 0.384); graft survival was 87% at 1 year and 81% at 2 years (91% at both 1 and 2 years in the control group, P = 0.260) [8]. In brief, in the literature, there is not enough experience on this critical, humanitarian topic.

Although the study by Assfalg et al. [6] has potential to clarify some controversial issues on this issue, it suffers from several limitations. Patient survival was significantly worse in HU transplants, and graft loss was similar in both HU and non-HU recipients. In HU patients transplanted due to ‘suicidality’, who were most likely in better physical health, patient survival was much better compared not only with the ‘lack of access’ group, but also with the control group, which implies that the heterogeneity of the HU group might have blunted the ultimate outcome of the patients. Secondly, the study does not disclose whether HU transplantations were clustered at some particular countries/centres or were homogeneous throughout the units, which might provide more information about the use of certain indications in some centres. Lastly, some important data (such as the indications for HU listing in the remaining 259 patients, waiting times among the subgroups, presence of diabetes or autoimmune diseases, detailed information on access issues, the aetiology of the primary diseases and the details of the listing circumstances), which could have impacted the results, were missing.

Despite the limitations, however, this is an important study that could stimulate discussion of the issue of HU transplant further in a wider forum such as a consensus conference. Owing to improved medical care leading to prolonged survival on dialysis [1], the number of patients experiencing vascular access problems and peritoneal failure, significant neuropathy or suicidal behaviour possibly will increase in the future [9]. Therefore, HU transplants could be needed even more frequently. On the other hand, the study by Assfalg et al. identified certain groups, such as patients with significant access issues and also patients being re-transplanted, clearly not benefiting from HU listing, raising more questions than answers. It is imperative for the transplant community to quickly establish standard, pragmatic and objective policies on HU transplantation that should try to balance the efficiency and fairness. Only then can we prevent any potential misuse of this humanitarian practice.

(See related article by Assfalg et al. High-urgency kidney transplantation in the Eurotransplant Kidney Allocation System: success or waste of organs? The Eurotransplant 15-year all-centre survey. Nephrol Dial Transplant 2016; 31: 1515–1522)

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