The UK operates two separate but interrelated schemes for the allocation of kidneys alone for end stage renal failure and the allocation of pancreas as simultaneous kidney/pancreas (SPK), pancreas transplant alone (PTA), pancreas after kidney transplant (PAK) or Islets for some patients with type I diabetes. The current national kidney allocation scheme (NKAS) was introduced in 2006 whilst the current national pancreas allocation scheme (NPAS) was introduced in 2010.
The NKAS that was in place prior to 2006 was based on a study which showed a significant effect of HLA matching on overall graft survival. The data showed that the best outcome was achieved with kidneys that had no mismatches at HLA-A, HLA-B, and HLA-DR loci (000 mismatches). The next most favourable outcome was achieved with one mismatch at either A or B loci or one mismatch at both the A and B , but no mismatch at the DR locus (100, 010, or 110 mismatches). These formed Tiers 1 and 2 of the old scheme. All other HLA matches formed part of Tier 3. The scheme included additional ranking within each tier prioritising paediatric patients over adults, highly sensitised patients over non sensitised patients and DR homozygous patients over non homozygous patients and local patients over national patients within a given tier. Whilst the scheme achieved its aim of improving HLA matching, the emphasis on well matched HLA resulted on iniquitous access for patients with rarer HLA types, predominantly those from ethnic minority populations.
The development of the current scheme for allocation of kidney took into account a number of factors which are known to influence post transplant outcome. These included donor factors, patient factors and transplant factors. Donor factors include age and cause of death. Donor age has been shown to have a significant effect on graft survival with a doubling of the risk of five year graft failure with donors over 60 years of age, compared to donors aged 18 – 30 years. The cause of death and therefore type of donor, Donation after Cardiac Death (DCD) versus Donation after Brain Death (DBD), also affects outcome.
Patient factors which have been shown to affect graft survival include age, length of time on the waiting list and primary renal disease. Patients aged 60 and above had an increased risk of transplant failure compared to patient aged 18 – 40 with a relative risk factor of about 1.5. In addition, patients who are on the waiting list for more than 6 months have a significantly increased risk of transplant failure in the first 3 months post transplant compared to patients on the waiting list for less than 6 months. Finally the patients underlying disease has an impact on transplant success, with patients with diabetes at the greatest risk of transplant failure.
Transplant factors which impact on graft survival include the year of transplant, the degree of HLA match between patient and donor and the ischemia time associated with the transplant. The year of transplant has an effect on transplant outcome with more recent transplants faring better due to improvements in surgical and laboratory techniques as well as improvements in immunosuppressive regimes. HLA matching has a significant effect on graft survival. Analysis of transplant data from the UK in the 1990’s and early 2000’s has identified four levels (graded levels 1 – 4) of HLA matching which correlate well with increasing risk of transplant failure. Level 1 comprises 000 HLA-A, B and DR mismatches, Level 2 comprises 0 HLA-DR and 0 or 1 HLA-B mismatch, Level 3 comprises 0 HLA-DR and 2 HLA-B mismatches or 1 HLA-DR and 1 HLA-B mismatch and Level 4 comprises 1 HLA-DR and 2 HLA-B mismatches or 2 HLA-DR mismatches. The UK data shows that HLA-A mismatches has no effect on transplant outcome. Finally UK data showed that there was no evidence of an increasing risk of transplant failure for cold ischemia time up to 21 hr, but beyond this, the risk of failure increased by 4% for each additional hour of ischemia time. Cold ischemia time is prolonged by long distance kidney exchange between centres and by reallocation of kidney to alternative patients following an unexpected positive crossmatch.
The current national kidney allocation scheme sought to address these issues. The objectives of the current scheme are to improve equity of access, to reduce the waiting times for patients on the transplant waiting list, to ensure that paediatric patients and highly sensitised patients who need well matched kidneys are prioritised for suitable kidneys, to maximise the life expectancy of a graft by age matching patients and donors and to reduce cold ischemia times.
The current UK national kidney allocation scheme is based on five Tiers labelled A to E based on HLA matching which avoids unacceptable mismatches, i.e. antibody specificities shown to be present, prioritising paediatric over adult patients and prioritising HLA DR homozygous patients. Tier A comprises 000 matched highly sensitised paediatric patients and 000 matched HLA-DR homozygous paediatric patients. Tier B comprises all other 000 matched paediatric patients. Tier C comprises 000 matched highly sensitised adult patients and 000 matched HLA-DR homozygous adult patients. Tier D comprises of all other 000 matched adult patients and all well matched paediatric patients (100, 010, and 110 HLA-A, -B, and -DR mismatches). All other patients are in Tier E. This system of tiers gives priority to paediatric patients over adult patients. It also recognises the difficulty associated with finding donors for highly sensitised patients and for HLA-DR homozygous patients. The scheme places well matched, what were previously known as favourably matched, paediatric patients in Tier D alongside adult 000 matched patients rather than in Tier E because the point system used to allocate priority within each tier would significantly disadvantage these patients should they be placed in Tier E.
Within each Tier, priority is assigned using a point scoring system which assigns scores either based entirely on waiting time (Tiers A and B) or based on 7 point scoring factors which are, waiting time, HLA match and age, age difference between patient and donor, location of the transplant centre in relation to the donor centre, HLA DR Homozygosity, HLA B Homozygosity and blood group.
The current scheme treats waiting time as the most influential of the point scoring factors as waiting time for transplant has been shown to have a significant effect on transplant outcome. For paediatric 000 matched patients, this is the only factor used to assign priority. For other paediatric patients and for all adults, the other factors are all scaled against waiting time.
The current scheme combines HLA match and age into a single factor and uses a formula which assigns more points to well matched younger patients so that HLA match is less important in older patients and more so in younger patients. This ensures that younger patients receive well matched kidneys, thereby minimising post transplant sensitisation and facilitating future re-transplant.
Points are deducted from the overall total for difference in age between donor and patients. The formula used ensures that small differences are not as influential as large differences. In addition, donors older than 50 are not used for paediatric patients as these have been shown to have poorer outcome.
The points awarded for patient location relative to donor location ensure that cold ischemia time is kept to a minimum. Patients in the donor centre are awarded more points than patients in the local geographical area, who are in turn awarded more points than other patients.
HLA DR homozygous patients and to lesser extent HLA B homozygous patient are harder to match for and risk accumulating on the waiting list. These patients are awarded extra points to reduce this risk.
Blood group identity is required but blood group compatibility is used in Tiers A – C. In Tiers D and E, blood group ‘A’ kidneys are offered to blood group AB patients and blood group ‘O’ kidneys are offered to blood group ‘B’ patients. Points are deducted from blood group B patients when they are offered a blood group O kidney.
The current scheme recognises the inequity of a system that relies heavily on HLA matching for patients with rare HLA type. Rather than award extra points for rare HLA types however, a system of defaulting of rare HLA types to more common related types is used. A patient with HLA type A36 for instance will be offered HLA-A1 kidneys. Similarly a patient with HLA type HLA-DR103 will be offered HLA-DR1 kidneys, antibodies permitting of course.
The current scheme has achieved many of its objectives in the first few years in use. The biggest impact has been on patient waiting times with a significant increase in transplant for patients waiting 5 or more years. Younger patients are receiving well matched kidneys as intended and the defaulting of rare HLA types has resulted in more transplants for patients with rarer HLA types.
The national pancreas allocation scheme (NPAS), which operates independently of but in an interrelated way with the NKAS, was updated in 2010, replacing a scheme that had been in place since 2003. The 2003 scheme placed emphasis on maintaining equity of access to organs through a managed balance of exchange (the difference between the number of exports and imports) rather than HLA match, though HLA antibodies present were of course taken into account. The general aim of the scheme was to minimise cold ischemia time and to maintain a balance of exchange between transplant centres. In addition, the 2003 scheme prioritised transplantation with the vascularised pancreas over Islet transplantation.
The current scheme covers all pancreatta donated after brain death (DBD) as well as those donated after cardiac death (DCD) and includes all simultaneous pancreas and kidneys, pancreas only and islets. Eligible patients include those listed for the different types of transplants – SPK, PTA, PAK and Islet transplantation.
Factors which may influence the outcome of a pancreas transplant depend on the type of pancreas transplant but generally include transplant factors, patient factors and donor factors and the current 2010 scheme takes all of these into account. The main transplant factor is the degree of HLA mismatch between patient and donor. Like the NKAS, the NPAS matches at HLA-A, B and DR. There is some evidence to suggest that poorly matched organs (5 or 6 mismatches at HLA-A, B and DR) have poorer long time post transplant survival. In addition, islet transplant patients are likely to require further transplant in later years and so keeping them from becoming sensitised is a legitimate clinical goal.
Patient factors include time on the waiting list, degree of sensitisation and dialysis status. Patients listed for priority islet transplants need to be transplanted quickly and this is reflected in the points system in the new scheme. Excessive waiting times have been shown to be associated with poor pancreas graft survival. Highly sensitised patients are more difficult to find a donor for and are as such at risk of accumulating on the waiting list and having much longer waiting times. Diabetes is often associated with chronic kidney disease which can lead to kidney failure requiring dialysis. Studies have shown that prolonged pre-transplant dialysis, particularly haemodialysis, is associated with a significantly increased rate of early pancreas graft loss.
Donor factors include age, weight and a combination of cause of death and cold ischemia time. Older donors and donors with high BMI have been shown to be associated with poorer long term survival of vascularised pancreas transplant and have historically been used preferentially for Islet transplantation. Long cold ischemia has a significant effect on graft survival but the impact varies depending on the cause of death. Organs retrieved from donors after cardiac death (donation after cardiac death – DCD) are very sensitive to ischemia and need to have as short an ischemia time as possible. Organs retrieved from donors after brain death (donation after brain death – DBD) are slightly more tolerant of ischemia than DCD organs but are also significantly affected.
The 2010 national pancreas allocation scheme takes most of these factors into account but prioritises blood group matching. As with the NKAS, for the NPAS, blood group identity is used instead of blood group compatibility so as not to disadvantage blood group ‘O’ patients by distributing blood group ‘O’ donors to all patients. Also like the kidney scheme, blood group ‘A’ pancreas are offered to blood group AB patients and blood group ‘O’ pancreas are offered to blood group ‘B’ patients. Further blood compatibility matching is undertaken if there are no suitable patients by blood group identity.
The 2010 scheme uses a point system with pancreas allocated to patient based on their Total Point Score (TPS). When organs become available, the kidneys are first offered through the NKAS for consideration for patients in Tiers A – C. If both kidneys are used, the pancreas are offered through the NPAS but only to patients listed for PTA, PAK or Islet transplant patients with the choice of patient depending on the total point score for each patient. If one or both kidneys are not allocated to a patient in Tier A – C, then they are offered through the pancreas scheme to patients listed for simultaneous pancreas and kidney transplant. Again the choice of patient will depend on their TPS. Should no suitable patient be found for SPK, the kidneys are offered back though the NKAS for patients in Tiers D and E and the pancreas are allocated through the NPAS to patients listed for PTA, PAK or Islet transplant.
The 2010 NPAS allocates points for HLA matches, patient waiting time, patient sensitisation, patient dialysis status, organ travel time, donor BMI and patient donor age match.
The points allocated for HLA matching recognise the deleterious effect of 5 or 6 mismatches at HLA-A, B and DR. Points are awarded for 4 or fewer mismatches, with no points awarded if there are 5 or 6 mismatches. In addition, to help reduce sensitisation in first Islet transplant, points are deducted for each mismatch for patients being considered for Islet transplant. Patients accumulate points for length of time on the waiting starting from the date on which they are first listed irrespective of periods of suspension. Patients for second or subsequent Islet transplantation accumulate points faster than other patients reflecting the clinical need of this group. Sensitised patients are awarded points such that patients with high calculated PRA (cPRA) have higher points than patients with lower cPRA to help improve the chances of these patients getting transplanted. Patients on dialysis are awarded extra points that are not awarded to patients who are not on dialysis. For DBD donors, patients in the three closest centres to the donor centre are awarded points that are not awarded to patients in other centres. Because of the urgent need to keep cold ischemia time to a minimum for DCD donors, patients in the centre closest to the donor centre are awarded a large number of points (30 times as many as are awarded for DBD donors). Patients in the next three closest centres are awarded half as many points and patients in other centres are not awarded any points. The points awarded for donor BMI favour patients listed for vascularised pancreas for low BMI donors whilst favouring patients listed for Islet transplant for donors with high BMI. Donor age match is not considered to be required clinically but is used as a tie breaker where patients otherwise have the same TPS. A small number of points are deducted from the patient score for age difference with more points deducted the larger the difference.
The overall effect of the 2010 point system for patients is that pancreatta are offered first to the centre with the patient with the highest score and in normal circumstances, only offered to other centres if the first centre declines. In normal circumstances the pancreatta are to be used for the patient they are allocated to through the scheme. If while the pancreatta are on route however it is discovered that they cannot be used for the named patients, due perhaps to the patient being too unwell for transplant for instance, the centre can allocate the pancreas to any of their patients. This minimises the cold ischemia time that would otherwise ensue if the pancreas were to be dispatched to the next patient on the list if that patient is at a different centre. Another scenario where they is a slight deviation from the offering order is if the pancreas is retrieved from the donor before being accepted by a transplant centre on behalf of their patient. In this rare scenario, a fast track process is followed in which the pancreatta are offered simultaneously to all pancreas transplant centres rather than in patient total point score order.
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