Kidney Allocation

24

Kidney Allocation DIANA A. WU, JAYME E. LOCKE, and JOHN L. R. FORSYTHE

CHAPTER OUTLINE

Two-Step Process General Points of Allocation United Kingdom United States

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.1

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.2,3 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.

Other Variations Eurotransplant Australia Summary

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.4,5 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.6 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.7,8 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.9 It follows that allocation systems mature to be an amalgam between markers of utility and factors associated with fairness (Table 24.1). 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.10 The most modern schemes attempt to predict the likely longevity of the transplanted kidney, advocating better matched 371

372

Kidney Transplantation: Principles and Practice

TABLE 24.1  Allocation Criteria Allocation Criteria

UK

US

Eurotransplant

Australia

HLA MM loci/importance Waiting time definition Definition of pediatric recipient

DR > B Listing date <18 years, retain pediatric priority until transplanted + + CRF ≥85%

DR only Start of dialysis <18 years

DR = B = A Start of dialysis <16 years or >16 yrs with growth potential on x-ray − + PRA >85% DR, B, A

DR > B/A Start of dialysis <18 years, first dialysis <17 years and on dialysis for >1 yr − − PRA >50% for 000 MM, >80% for all other MM levels −

+ + Medical urgency AMP ESP

+ + Around 80% of kidneys allocated within donor state via state-based algorithms

Recipient age (adults) Donor-recipient age matching Definition of highly sensitized recipient Priority for HLA homozygous recipients Local allocation priority Balance of exchange Other allocation criteria/ features

DR, B

+ − Sliding scale for CPRA 20–100 −

+ − Defaulting of rare HLA antigens HLA match and age combined

+ − Priority for previous living organ donors EPTS KDPI

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. Sources: UK: NHS Blood and Transplant policy 186/9, effective 26/01/18. Available online at: https://nhsbtdbe.blob.core.windows.net/umbraco-assetscorp/6522/pol186-kidney-transplantation-deceased-donor-organ-allocation.pdf. US: Organ Procurement and Transplantation Network policy 8, effective 08/10/17. Available online at: https://optn.transplant.hrsa.gov/media/1200/optn_ policies.pdf#nameddest=Policy_08. Eurotransplant: Eurotransplant foundation manual, Chapter 4, version 5.2, effective 11/11/16. Available online at: https://www.eurotransplant.org/cms/m ediaobject.php?file=H4+ETKAS+November+11%2C+20161.pdf. Australia: The Transplantation Society of Australia and New Zealand, version 1.1, effective 17/05/17. Available online at: https://www.tsanz.com.au/organa llocationguidelines/documents/ClinicalGuidelinesV1.1May2017.pdf.

United Kingdom

Fig. 24.1  Marginal donor kidney.

kidneys for those who are younger, and accepting a more poorly matched kidney for those patients who, on balance, have fewer years to survive.11 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. Although these themes are universal, the national response has been varied depending on the prevailing clinical, patient, and political views.11 We will describe here two notable schemes and summarize the variation in some others. 

The first UK national scheme began in 1989 with a simple HLA match allocation.12 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.13 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.5 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.13 As a result a new allocation scheme was derived and introduced in 2006, which is still in place at the time of this writing.14 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

24 • Kidney Allocation

373

1600 1400

Number of donors

1200 70 or over 1000

60–69 50–59

800

18–49 0–17

600 400 200 0 2006/07 2007/08 2008/09 2009/10 2010/11 2011/12 2012/13 2013/14 2014/15 2015/16

Fig. 24.2  Age of deceased donors in the UK.

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.14 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.11,15 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. 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 index16 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.17 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.18 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.18 However, HLA subtype matching was not completely abandoned from the allocation policy. Secondary to

374

Kidney Transplantation: Principles and Practice 100 Pre 2006 scheme

Post 2006 scheme

90

981

80

60 50 538

497

441 429 392 370

30

205

Highly sensitized

Waiting time

95 11 31

2 6 Not reported

Black

43

Other

96

53 70

Asian

1–3 years

48 <1 year

Difficult

Moderate

Matchability

159

White

143 53

Easy

0

236

≥7 years

10

195

5–7 years

207 165

20

326

3–5 years

40

512

CRF ≥85%

% DBD kidney transplants

824 70

Recipient ethnicity

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.)

racial differences in locus allele frequency, HLA subtype matching was shown to be disadvantageous to minorities, limiting their access to deceased donor transplantation.19 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.20,21 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.22,23 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 priority18,24:   

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. □ 

  

24 • Kidney Allocation

375

TABLE 24.2  The US Kidney Allocation System Allocation Sequence Sequence A KDPI ≤20%

Sequence B KDPI >20% but <35%

Sequence C KDPI ≥35% but ≤85%

Sequence Da KDPI >85%

Local CPRA 100 Regional CPRA 100 National CPRA 100 Local CPRA 99 Regional CPRA 99 Local CPRA 98 Zero mismatch (top 20% EPTS) Prior living donor Local pediatrics Local top 20% EPTS Zero mismatch (all) Local (all) Regional pediatrics Regional (top 20%) Regional (all) National pediatrics National (top 20%) National (all)

Local CPRA 100 Regional CPRA 100 National CPRA 100 Local CPRA 99 Regional CPRA 99 Local CPRA 98 Zero mismatch Prior living donor Local pediatrics Local adults Regional pediatrics Regional adults National pediatrics National adults

Local CPRA 100 Regional CPRA 100 National CPRA 100 Local CPRA 99 Regional CPRA 99 Local CPRA 98 Zero mismatch Prior living donor Local Regional National

Local CPRA 100 Regional CPRA 100 National CPRA 100 Local CPRA 99 Regional CPRA 99 Local CPRA 98 Zero mismatch Local + regional National

aAll

categories in Sequence D are limited to adult 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.25 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 A2 and A2B 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.26 KDPI replaced SCD and ECD definitions and provides increased precision in determining organ quality.27,28 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.27 A lower KDPI is associated with better posttransplant survival.28 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. EPTS is used to estimate posttransplant survival of recipients and to risk-stratify patients into two broad groups (≤20% vs. 21%–100%) based on four variables: recipient age, diabetic status, time on dialysis, and number of prior solid-organ transplants.29 Because candidates with EPTS scores ≤20% have the longest estimated posttransplant survival, they are prioritized to receive kidney offers from donors with KDPI ≤20%. In general, older age, longer dialysis duration, prior solid-organ transplant, and the presence of diabetes are associated with higher EPTS scores.26 KAS also revised candidate allocation points to reflect updated goals. Specifically, waiting-time points now begin at dialysis or listing with glomerular filtration rate (GFR) ≤20 mL/min and cPRA priority awards additional points to candidates with highest level of sensitization. All candidates are ranked by points within their EPTS group. Data from the first 18 months since implementation of KAS were reviewed. Post-KAS there has been a 6.9% increase in solitary deceased donor kidney transplants observed nationally; however, the geographic distribution of this increased volume was not consistent across regions.30,31 In fact, most UNOS regions saw only modest changes in volume with the largest relative increase occurring in region 9 and the largest relative decrease in region 6 (Fig. 24.4). The proportion of transplants occurring in patients with cPRA 99% to 100% initially rose from 2.4% of all deceased donor transplants performed each month to over 17% immediately after KAS implementation. By 18 months post-KAS the proportion had decreased and plateaued to approximately10% of all transplants.31 In addition, KAS improved patient access to deceased donor transplantation for historically disadvantaged

376

Kidney Transplantation: Principles and Practice

6

20

7

6

17.518.0 17.2

18

8

5

11

Percentage of kidney transplants

16

6

14.2 13.9 13.3 13.0 12.9 12.6

3

Pre KAS (1 year) Post KAS (12 months) Post KAS (18 months)

12

11.3 10.9

9.7 9.6 9.4

10 8

7.0 6.46.7

6

4.5 3.8

3.9 3.4 3.6 4

9 2

3

4

14

1 10

7.0 6.4 6.4

10.8

7.8 6.9 7.6 7.4 6.7 6.2

3.8

2 0

1

2

3

4

5

6 7 OPTN region

8

9

10

11

Fig. 24.4  Geographic distribution of deceased donor kidney transplants in the US pre- and post-KAS implementation. 80

Pre KAS (1 year) 6 months post KAS

Discard rates (%)

59.9 59.3 54.8 56.6

1 year post KAS

60

18 months post KAS

40

20 2.6 0

20.3 20.7 18.5 18.5

20.0 18.2 .17.0 17.8

2.0 2.5 2.2 0-20

6.4 7.5 5.8.5.4 21-34

35-85 KDPI (%)

86-100

Overall

Fig. 24.5  US deceased donor kidney discard rates pre- and post-KAS implementation.

groups. Specifically, in the first 18 months since implementation there has been a 16.6% relative increase in transplants among African American candidates. Moreover, there was a 33% increase in transplantation among candidates with ≥5 and <10 years dialysis time and 138% increase among candidates with ≥10 years dialysis time. There has also been a 449% increase in ABO-compatible (e.g., A2 and A2B donor kidneys to B recipients) transplants.30 Longevity mismatches have also decreased in the first year post-KAS implementation. The percentage of recipients aged ≥65 years receiving KDPI <20% kidneys decreased from 3.2% to 1.1%, and concurrently the number of recipients aged <40 years receiving KDPI <20% kidneys increased by 81.7%.30,31 Not surprisingly, the gap between donor and recipient age decreased significantly in the first year post-KAS.

Whereas implementation of KAS has resulted in several “big wins,” it is important to note several unintended consequences. Specifically, the percentage of kidneys distributed outside the recovering OPO’s donor service area increased in the first year post-KAS, and as such, there was a significant increase in the frequency of CIT exceeding 24 hours.30 Rates of delayed graft function (DGF) also increased in the first 18 months postKAS from 24.4% to 29.5%.30,31 Despite increases in CIT and DGF, graft survival rates in the first 6 months postKAS have remained similar. Finally, although transplant volume increased with implementation of KAS so too have discard rates, and discard has been most pronounced among donor kidneys with KDPI ≥85% (Fig. 24.5).30,31

24 • Kidney Allocation

Without question the full effect of KAS has yet to be appreciated. Longer follow-up will be needed to better assess patient and graft outcomes, transplant volumes, and discard rates, and to ensure that the stated goals of improving access for vulnerable populations persists. 

Other Variations EUROTRANSPLANT This scheme, one of the longest running, has a number of distinctive features. First, it has medical urgency as a factor in the allocation score.32 Second, rather than being defined by a strict age cutoff, pediatric status (and therefore priority) is granted to any patient demonstrating growth potential on x-ray.32 Third, an acceptable mismatch program was introduced as early as 1996 for those patients who are highly sensitized.33 Finally, in the Eurotransplant Senior program, running since 1999 and colloquially referred to as the “old for old” scheme, nonsensitized patients aged over 65 have priority for donors aged over 65 irrespective of HLA matching.34 Overall the Eurotransplant scheme has a good record in achieving transplantation for long waiting, highly sensitized, and difficult to match patients. This may be, in part, because of the international nature of the organ allocation organization.35,36 

AUSTRALIA Australia is notable for strict entry criteria to the waiting list with national agreement for patients to have an estimated 5-year survival of >80% post transplantation. Only wellmatched grafts are shared nationally and approximately 80% are allocated by state protocols, which are encouraged to weight waiting time heavily to improve access for those who have been on the list for a long time.37 

Summary The uplifting effect of being chosen to receive a kidney, or the polar opposite effect of living on the list for years with no call, define the need for transparent, objective policies of allocation that are monitored diligently and reviewed regularly. The World Health Organization and the Declaration of Istanbul have set out principles to be followed.38,39 The latter reminds us that clear programs with visible accountability are needed, otherwise the vacuum is filled by illegal organ trafficking and transplant tourism. The strong effect of HLA matching, especially in the earlier eras when immunosuppression was less effective, means that allocation algorithms have been built around this central factor. But this has caused inequity, especially where ethnic minorities with rare HLA types make up a significant part of the population. This is compounded when those same groups have a predilection for renal disease and a cultural background that makes deceased organ donation less frequent. Different nations balance utility and equity in ways that feel comfortable to their medical and social context. The

377

increased use of points systems brings objectivity and gives reassurance to patients. It also allows the use of computer simulations as new iterations of the allocation algorithm are designed. These simulations have become a valuable tool that allows the designers to see the predicted consequences of minor alterations in the points scoring schemes. It is quite possible that artificial intelligence will plan allocation systems in the future. In the meantime we must continue to monitor present schemes and fine tune them to improve the balance between conflicting principles that govern allocation.

References 1. Gutmann T, Land W. The ethics of organ allocation: the state of debate. Transplant Rev 1997;11(4):191–207. 2. Oniscu GC, Schalkwijk AAH, Johnson RJ, Brown H, Forsythe JLR. Equity of access to renal transplant waiting list and renal transplantation in Scotland: cohort study. BMJ 2003;327(7426):1261. 3. Akolekar D, Oniscu GC, Forsythe JL. Variations in the assessment practice for renal transplantation across the United Kingdom. Transplantation 2008;85(3):407–10. 4. Meier-Kriesche H-U, Port FK, Ojo AO, et al. Effect of waiting time on renal transplant outcome. Kidney Int 2000;58(3):1311–7. 5. Johnson RJ, Fuggle SV, O’Neill J, et  al. Factors influencing outcome after deceased heart beating donor kidney transplantation in the United Kingdom: an evidence base for a new national kidney allocation policy. Transplantation 2010;89(4):379–86. 6. Morris PJ, Johnson RJ, Fuggle SV, Belger MA, Briggs JD. Analysis of factors that affect outcome of primary cadaveric renal transplantation in the UK. HLA task force of the kidney advisory group of the United Kingdom Transplant Support Service Authority (UKTSSA). Lancet 1999;354(9185):1147–52. 7. Gilks WR, Bradley BA, Gore SM, Klouda PT. Substantial benefits of tissue matching in renal transplantation. Transplantation 1987;43(5):669–74. 8. Takemoto S, Terasaki PI, Cecka JM, Cho YW, Gjertson DW. Survival of nationally shared, HLA-matched kidney transplants from cadaveric donors. N Engl J Med 1992;327(12):834–9. 9. Rudge C, Johnson RJ, Fuggle SV, Forsythe JL. Renal transplantation in the United Kingdom for patients from ethnic minorities. Transplantation 2007;83(9):1169–73. 10. Ross LF, Parker W, Veatch RM, Gentry SE, Thistlethwaite Jr JR. Equal opportunity supplemented by fair innings: equity and efficiency in allocating deceased donor kidneys. Am J Transplant 2012;12(8): 2115–24. 11. Wu DA, Watson CJ, Bradley JA, et al. Global trends and challenges in deceased donor kidney allocation. Kidney Int 2017;91(6):1287–99. 12. Fuggle SV, Johnson RJ, Rudge CJ, Forsythe JL. Human leukocyte antigen and the allocation of kidneys from cadaver donors in the United Kingdom. Transplantation 2004;77(4):618–20. 13. Fuggle SV, Johnson RJ, Bradley JA, Rudge CJ. Impact of the 1998 UK national allocation scheme for deceased heartbeating donor kidneys. Transplantation 2010;89(4):372–8. 14. Johnson RJ, Fuggle SV, Mumford L, et  al. A new UK 2006 national kidney allocation scheme for deceased heart-beating donor kidneys. Transplantation 2010;89(4):387–94. 15. NHS Blood and Transplant. Kidney Advisory Group. Policy POL186/7. Kidney transplantation: deceased donor organ allocation Bristol 2017. Available online at:https://nhsbtdbe.blob.core.windows.net/umbracoassets-corp/4368/kidney_allocation_policy.pdf [accessed 30.08.17]. 16. Watson CJ, Johnson RJ, Birch R, Collett D, Bradley JA. A simplified donor risk index for predicting outcome after deceased donor kidney transplantation. Transplantation 2012;93(3):314–18. 17. Organ Procurement and Transplantation Network Database. Available online at: https://optn.transplant.hrsa.gove/data/view-datareports/national-data/# [accessed 26.09.17]. 18. Smith JM, Biggins SW, Haselby DG, et al. Kidney, pancreas and liver allocation and distribution in the United States. Am J Transplant 2012;12(12):3191–212. 19. Roberts JP, Wolfe RA, Bragg-Gresham JL, et  al. Effect of changing the priority for HLA matching on the rates and outcomes of kidney transplantation in minority groups. N Engl J Med 2004;350: 545–51.

378

Kidney Transplantation: Principles and Practice

20. Ashby VB, Port FK, Wolfe RA, et al. Transplanting kidneys without points for HLA-B matching: consequences of the policy change. Am J Transplant 2011;11:1712–8. 21. Hall EC, Massie AB, James NT, et  al. Effect of eliminating priority points for HLA-B matching on racial disparities in kidney transplant rates. Am J Kidney Dis 2011;58:813–6. 22. Ojo AO, Hanson JA, Meier-Kriesche H, et al. Survival in recipients of marginal cadaveric donor kidneys compared with other recipients and wait-listed transplant candidates. J Am Soc Nephrol 2001;12:589–97. 23. Stratta RJ, Rohr MS, Sundberg AK, et  al. Increased kidney transplantation utilizing expanded criteria deceased donors with results comparable to standard criteria donor transplant. Ann Surg 2004;239:688–97. 24.  Organ Procurement and Transplantation Network website. Available online at: https://optn.transplant.hrsa.gov/governance/policies/ [accessed 2018]. 25. Kidney Allocation System (KAS) Clarifications and Clean Up. Available online at:https://optn.transplant.hrsa.gov/media/1239/04_kas -clarifications.pdf [accessed 26.09.17]. 26. Israni AK, Salkowski N, Gustafson S, et  al. New national allocation policy for deceased donor kidneys in the United States and possible effect on patient outcomes. J Am Soc Nephrol 2014;25(8):1842–8. 27. Guide to calculating and interpreting KDPI. Available online at:https:// optn.transplant.hrsa.gov/media/1512/guide_to_caculating_interpr eting_kdpi.pdf [accessed 26.09.17]. 28. Stewart D, Samana C, Cherikh W, et al. Has displaying KDPI in DonorNet® led to a spike in discard rates for lower quality kidneys? Am J Transplant 2013;13:(S5). 29. A guide to calculating and interpreting the Estimated Post-Transplant Survival (EPTS) score used in the kidney allocation system (KAS). Available online at:https://optn.transplant.hrsa.gov/media/1511/ guide_to_calculating_interpreting_epts.pdf [accessed 26.09.17]. 30. Stewart DE, Kucheryavaya AY, Klassen DK, Turgeon NA, Formica RN, Aeder MI. Changes in deceased donor kidney transplantation one year after KAS implementation. Am J Transplant 2016;16(6):1834–47.

31. The new kidney allocation system (KAS): the first 18 months. UNOS Transplant Pro website. Available online at: https://www.transplant pro.org/news/kidney/18-month-analysis-shows-progress-in-kidneyallocation-system [accessed 26.09.17]. 32. Eurotransplant. Eurotransplant Manual Version 5.2. Chapter 4 Kidney (ETKAS and ESP) Leiden 2016. Available online at: https://www.eur otransplant.org/cms/mediaobject.php?file=H4+ETKAS+November+ 11%2C+20161.pdf [accessed 30.08.17]. 33. Claas FH, Rahmel A, Doxiadis II . Enhanced kidney allocation to highly sensitized patients by the acceptable mismatch program. Transplantation 2009;88(4):447–52. 34. Frei U, Noeldeke J, Machold-Fabrizii V, et al. Prospective age-matching in elderly kidney transplant recipients—a 5-year analysis of the Eurotransplant Senior Program. Am J Transplant 2008;8(1):50–7. 35. Persijn GG, Smits JM, Smith M, Frei U. Five-year experience with the new eurotransplant kidney allocation system, 1996 to 2001. Transplant Proc 2002;34(8):3072–4. 36. Persijn GG, Smits JM, Frei U. Three-year experience with the new eurotransplant kidney allocation system. Nephrol Dial Transplant 2001;16(Suppl 6):144–6. 37. The Transplantation Society of Australia and New Zealand. Clinical Guidelines for Organ Transplantation from Deceased Donors. Chapter 5 Kidney; 2017. Available online at: https://www.tsanz.com.au/organal locationguidelines/documents/ClinicalGuidelinesV1.1May2017.pdf [accessed 30.08.17]. 38. Steering Committee of the Istanbul Summit. Organ trafficking and transplant tourism and commercialism: the declaration of Istanbul. Lancet 2008;372(9632):5–6. 39. World Health Organization guiding principles on human cell, tissue and organ transplantation. 2010. Available online at:http://www.who. int/transplantation/Guiding_PrinciplesTransplantation_WHA63.22 en.pdf?ua=1.