Kidney Allocation





It is a favorite assertion of the authors that clinical transplantation is an excellent example of “medical ethics in practice.” Perhaps this is best demonstrated by the processes of organ allocation where a balance must be struck between allocation that makes best use of a scarce resource and the principle of equitable access to all on the waiting list.


Two-Step Process


It is important to acknowledge that, for the patient to receive an offer of a deceased donor kidney, they must have completed a two-step process. First, the patient must gain access to the waiting list. The preparation for listing and the criteria for this are covered elsewhere (see Chapter 4 ), but this is an important step and there is evidence of inequity in clinical processes to screen patients for access to the waiting list. This chapter will concentrate on the second step, which is allocation of a donor kidney to a patient who is already on the waiting list.




General Points of Allocation


As transplantation from deceased donors develops in any particular country, the sophistication of allocation processes also matures. Early allocation plans may begin with a local clinician picking from a list of local patients, a system that is subjective, open to challenge, and does not maximize population size for matching. Allocation algorithms then develop regionally, and eventually result in a complex process that is usually run on a national basis by a designated organization. On occasion, an international collaboration is set up—perhaps the most notable example of this is Eurotransplant, which covers the nations of Germany, Belgium, Austria, Netherlands, Luxembourg, Slovenia, Croatia, and Hungary. The more advanced allocation schemes are safeguarded by legislative frameworks and appropriate governance processes.


The ethical dilemma in the design of allocation policies faced by all countries is the balance between utility and equity.


Utility-based allocation gives priority to those with the best chance of a favorable outcome—by this method gaining the maximum benefit from every transplanted kidney. Although this is a clear principle, the secondary question of how to measure the benefit is much more difficult to answer. Should this be based on survival statistics (kidney or patient), comparative benefit of life years gained, or should we include quality of life for each of the possible patients? In addition, an allocation system based purely on utility causes disadvantage to many patient groups—the elderly, diabetics, and those who have waited for a longer time.


On the other hand, equity, the concept that each patient should have an equal chance of receiving an offer, will result in a system that does not maximize the precious gift of a donor organ. For instance, a “queuing” or “first-come first-served” system gives priority to more elderly patients and those who have been on dialysis longer with more comorbidity, which mitigates against the best results.


Most allocation systems around the world were built on human leukocyte antigen (HLA) matching between donor and recipient. This stands to reason as a better match produces better survival. However, the unintended consequence of this allocation principle is that patients with rare HLA types (who also happen to be ethnic minorities in any community) and sensitized patients (who also happen to be mainly female) are disadvantaged.


It follows that allocation systems mature to be an amalgam between markers of utility and factors associated with fairness ( Table 24.1 ).



Table 24.1

Allocation Criteria








































































Allocation Criteria UK US Eurotransplant Australia
HLA MM loci/importance DR > B DR only DR = B = A DR > B/A
Waiting time definition Listing date Start of dialysis Start of dialysis Start of dialysis
Definition of pediatric recipient <18 years, retain pediatric priority until transplanted <18 years <16 years or >16 yrs with growth potential on x-ray <18 years, first dialysis <17 years and on dialysis for >1 yr
Recipient age (adults) + +
Donor-recipient age matching + +
Definition of highly sensitized recipient CRF ≥85% Sliding scale for CPRA 20–100 PRA >85% PRA >50% for 000 MM, >80% for all other MM levels
Priority for HLA homozygous recipients DR, B DR, B, A
Local allocation priority + + + +
Balance of exchange + +
Other allocation criteria/features Defaulting of rare HLA antigens
HLA match and age combined
Priority for previous living organ donors
EPTS
KDPI
Medical urgency
AMP
ESP
Around 80% of kidneys allocated within donor state via state-based algorithms

AMP , acceptable mismatch programme; CPRA , calculated panel reactive antibody; CRF , calculated reaction frequency; EPTS , estimated post transplant survival score; ESP , Eurotransplant seniors program; HLA , human leukocyte antigen; KDPI , kidney donor profile index; MM , mismatch; PRA , panel reactive antibody.


Age is also a controversial issue in allocation policies. Few would deny priority for pediatric patients because of the natural emotional response to help children, backed by the clinical issues peculiar to children with renal failure, including growth and developmental delay. Yet some systems have a strict cutoff between designation of a patient as a pediatric or adult, which seems harsh on the young person who has only strayed 1 day into the adult sector, losing all priority in the process. In addition, any priority for younger patients (even though utility would suggest that they will benefit to a greater extent) is often resisted and can be characterized as age discrimination. Some have advocated that the allocation of younger donor kidneys should be reserved for younger recipients (obviously accompanied by older donor kidneys allocated to older recipients) because this treats all patients in an age-matched fashion. The most modern schemes attempt to predict the likely longevity of the transplanted kidney, advocating better matched kidneys for those who are younger, and accepting a more poorly matched kidney for those patients who, on balance, have fewer years to survive.


Finally, the characteristics of donors have changed rapidly in recent years. More aged, higher body mass index (BMI), and more comorbidity in donors has been well demonstrated, resulting in terms such as “marginal” or “extended criteria” donor ( Figs. 24.1 and 24.2 ). The fair method of allocation that also gives maximum benefit of these donor kidneys provides a significant challenge for national transplant organizations.




Fig. 24.1


Marginal donor kidney.



Fig. 24.2


Age of deceased donors in the UK.


Although these themes are universal, the national response has been varied depending on the prevailing clinical, patient, and political views. We will describe here two notable schemes and summarize the variation in some others.




United Kingdom


The first UK national scheme began in 1989 with a simple HLA match allocation. This was still a hybrid scheme in that one kidney from each donor was allocated nationally, whereas the paired kidney was allocated locally, governed by individual center policies. This was revised in 1998 after analysis of outcome had shown three distinct tiers of HLA mismatch as factors in graft survival. Both kidneys were allocated on a national basis in the 1998 scheme, which also introduced a number of novel allocation tools including a points score to differentiate equally well-matched (or equally poorly matched) patients within each tier. The points were based on donor recipient age difference, recipient age, waiting time, matchability score, sensitization level, and, as a compromise to those centers who wished to maintain a local organ allocation flavor, points for balance of organ exchange among centers. Matchability was a measure of the probability of a particular patient being offered a well-matched kidney—this was a correction factor for those patients who were “difficult to match.”


This scheme was analyzed around 8 years later and inequity of access, as an unintended consequence of the dominance of HLA matching, was seen to be a significant problem. As a result a new allocation scheme was derived and introduced in 2006, which is still in place at the time of this writing.


The new scheme placed less emphasis on HLA matching although zero HLA mismatched patients retained top priority and well-matched patients (100, 10, and 110) also had some level of priority. Highly sensitized patients were also seen to benefit. For each patient a “calculated reaction frequency” was measured. This was defined as the percentage of 10,000 recent donors to which the patient has preformed antibodies and when this rose to over 85%, the patient was deemed highly sensitized and gained priority. A novel approach was developed to tackle the inequity of access experienced by patients with rare HLA types, whereby rare HLA antigens (with a frequency of less than 2% in the donor pool) were defaulted to close counterparts based on serologic reactivity data. For instance, the rare antigen B82 was defaulted to B12, opening up 18% of the donor pool. The points score was also adapted to give much more weight to waiting time, as a result of patient input to the design of the scheme. Finally, points for recipient age were combined with the HLA match to give the best matched kidneys to younger patients.


It is important to note that the cold ischemic time (CIT) was also monitored as the new scheme came in. A surrogate for this factor—proximity of the donor to the recipient center—was included in the points score and, gratifyingly, the CIT actually decreased over the introduction of the 2006 scheme.


In 2014 the scheme was extended to kidneys donated from donors after circulatory death (DCD), using the same algorithm but based on regional rather than fully national allocation, to minimize CIT.


The 2006 scheme was reviewed and found to have increased the number of transplants for long-waiting and highly sensitized patients ( Fig. 24.3 ). Although the percentage of difficult to match and minority ethnic patients transplanted had also increased, significant inequity remained, reflecting the immense challenge of achieving a good balance between utility and equity.




Fig. 24.3


Effect of UK 2006 National Kidney Allocation scheme. DBD , donors after brain death; CRF , calculated reaction frequency.

Based on NHS Blood and Transplant data from 2003 versus 2013.


Work began on a new allocation algorithm in 2016 and it is hoped that the new scheme will be introduced in 2019. It is designed to further improve inequities of access, particularly to highly sensitized or difficult to match patients. In addition, it is planned that there will be better matching between the risk of a donor kidney as determined by a donor risk index and the perceived risk associated with a particular recipient. In this manner simulations suggest that the potential of a particular kidney can be better matched to the needs of the allocated recipient.




United States


Although the number of kidney transplants performed in the US has increased over the years, there remains a critical organ shortage. In fact, as of September 2017, more than 96,000 people were waiting for a deceased donor kidney in the US; yet fewer than 20,000 receive a kidney transplant each year.


Efforts to address this critical shortage and improve organ matching and placement resulted in the US Congress passing the National Organ Transplant Act (NOTA) in 1984. NOTA (1) established the Organ Procurement and Transplantation Network (OPTN) to maintain a national registry for organ matching, and (2) required the OPTN to be operated by a private, nonprofit organization under federal contract, effectively creating the United Network for Organ Sharing (UNOS; the OPTN contractor). The goal of US allocation policy has been to balance utility and equity regarding the distribution of deceased donor organs. Not surprisingly, the policy has changed over time to optimize allocation efforts aimed at balancing these often competing goals.


Initially, US allocation policy focused heavily on donor and recipient HLA matching; over time, however, advances in immunosuppression regimen resulted in lower acute rejection rates, and in 1995 allocation points awarded based on HLA-A matching were eliminated and more emphasis was placed on waiting time. The concept of first come, first transplanted was introduced.


However, HLA subtype matching was not completely abandoned from the allocation policy. Secondary to racial differences in locus allele frequency, HLA subtype matching was shown to be disadvantageous to minorities, limiting their access to deceased donor transplantation. As a result, in 2003 allocation points based on HLA-B matching were eliminated. Subsequent studies demonstrated that these policy changes were effective in mitigating racial disparities with no adverse effect on graft survival. Unfortunately, these policy changes did not eliminate racial disparities in deceased donor transplantation rates.


Other allocation policy changes (circa 2002) have focused on expanding the deceased donor pool to include those kidneys previously deemed not suitable for transplant—the concept of expanded criteria donor (ECD) kidneys and DCD kidneys. ECD was defined as kidneys from any brain dead donor ≥60 years or aged 50 to 59 years with at least two of the following: history of hypertension, serum creatinine >1.5 mg/dL, or cause of death from cerebrovascular accident. Receipt of an ECD kidney conferred a 1.7-fold higher risk for graft failure compared with a standard criteria donor (SCD) kidney; however, studies consistently demonstrated ECD kidney transplantation was associated with a significant survival benefit over remaining on dialysis. These changes resulted in an allocation system that categorized donors into four mutually exclusive groups: SCD <35 years, SCD ≥35 years, ECD, and DCD. Within each category, several principles dictated allocation priority :




  • Candidates are listed for simultaneous kidney and nonkidney organ transplants.



  • Candidates with zero antigen mismatch with the donor kidney (accepting organ procurement organization [OPO] must “pay back” a kidney to a common national pool).



  • Candidates are assigned points enabling ranking within each group:




    • Waiting time (begins at time of listing; listing requirement = maintenance dialysis or glomerular filtration rate ≤20 mL/min)



    • Number of antigen mismatches between donor and candidate at the DR locus



    • Calculated panel reactive antibody (cPRA) ≥80%



    • Adherence to geography: local → regional → national; at each geographic level candidates were rank ordered according to the point system



    • Pediatric candidates (<18 years) were given priority ahead of adult candidates within each geographic level for nonzero mismatch kidney offers from donors <35 years.



    • Kidneys were distributed to ABO identical candidates first, then to ABO-compatible candidates.




Despite the numerous allocation policy changes since the OPTN’s inception in 1984, variability in access to transplantation by candidate blood type, high kidney discard rates, unrealized graft years, and high retransplant rates persisted. Thus in December 2014 the new Kidney Allocation System (KAS) was implemented with the stated goals to make the most of every donated kidney without diminishing access, promote graft survival for those at highest risk for retransplant, minimize loss of potential graft function through better matching, improve efficiency and utilization by providing better information about kidney offers, provide comprehensive data to guide transplant decision making, and reduce differences in access for ethnic minorities, pediatric candidates, and sensitized candidates. To accomplish these stated goals designed to balance equity and utility, KAS resulted in system-wide changes:




  • Kidney donors scored by the Kidney Donor Profile Index (KDPI)



  • Candidates classified by Estimated Post-Transplant Survival (EPTS) score



  • Waiting time calculation begins at initiation of dialysis (not time of listing) or at time of preemptive listing



  • cPRA priority points allocated using sliding scale



  • Pediatric (<18 years) allocation priority for kidneys with KDPI <0.35



  • Points for pediatric candidates when offered a zero antigen mismatch



  • Blood type B candidates eligible to accept kidneys from A 2 and A 2 B donors



  • Elimination of kidney “pay back” policy



  • Elimination of kidney variances



To improve efficiency and organ utilization, KAS uses KDPI to risk-stratify donors and EPTS is used to risk-stratify recipients. KDPI replaced SCD and ECD definitions and provides increased precision in determining organ quality. To maximize matching between graft and recipient longevity, KAS prioritizes recipients with EPTS scores <20% with donor kidneys with KDPI <20%.


KDPI is a measure of relative risk derived from the Kidney Donor Risk Index (KDRI) on a cumulative percentage scale, and is calculated using 10 donor criteria—age, height, weight, ethnicity, history of hypertension, history of diabetes, cause of death, serum creatinine, hepatitis C virus, and DCD. A lower KDPI is associated with better posttransplant survival. Similar to the previous allocation scheme, KDPI is now utilized to categorize donor kidneys into four mutually exclusive sequences: (1) KDPI ≤20% (0.20), (2) KDPI >20% (0.20) but <35% (0.35), (3) KDPI ≥ 35% (0.35) but <85% (0.85), and (4) KDPI ≥85% (0.85; Table 24.2 ). Sequence D (KDPI ≥85%) reflects a similar quality of kidney as the previous ECD definition (higher risk for graft failure), and as such, requires a separate approval and consent for eligibility.


Dec 26, 2019 | Posted by in NEPHROLOGY | Comments Off on Kidney Allocation

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