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THE PORTUGUESE MATCH ALGORITHM
IN THE KIDNEY PAIRED DONATION PROGRAM
Bruno A. Lima1
, Leonídio Dias2
, António C. Henriques2
, Helena Alves1
1
Centro de Histocompatibilidade do Norte, Porto, Portugal
2
Serviço de Nefrologia, Centro Hospitalar do Porto, Hospital de Sto António, Porto, Portugal
Keywords - Kidney paired donation, kidney transplantation, live donation, match algorithm
Summary - The growing disparity between the number of patients on the national list waiting for a kidney transplant
and the number of deceased donors has compelled transplant programs to seek ways to increase the number of organs
available for transplantation. Rapaport formulated the principle of paired exchange in 1986, giving it the title “kidney
paired donation” (KPD). Individuals who are unable to donate a kidney to a loved one due to immunologic incompatibility
are exchanged in order to form compatible pairs; the volunteers thus become living donors for unknown recipients. The
aim of this study is to describe the algorithm for the Portuguese KPD program that will being in 2009.
Data were used from five patients with an incompatible blood type living donor and eight patients, each with a positive
crossmatch living donor; one of the latter recipients had four positive crossmatch living donors.
We present a computer match that selects exchange combinations with the following hierarchy: 1) maximum number of
matched pairs; 2) blood type O recipients are given priority in receiving from blood type O donors; 3) pairs with a higher
donor/recipient average match score. With a sample of thirteen incompatible donor/recipients pairs, we were able to
define seven possible transplants.
The algorithm described helped to ensure an allocation program that was as equitable as possible based on medical criteria
without compromising the possible number of transplants.
ORGANS, TISSUES & CELLS, (13), 25-32, 2010
Mailing address: Bruno A Lima, Centro de Histocompatibilidade do
Norte, Rua Dr Roberto Frias, 4200-467 Porto, Portugal;
e-mail: bruno@chnorte.min-saude.pt
Introduction
Kidney transplantation improves and extends the lives of
patients with end-stage renal disease (ESRD). Transplanta-
tion is less costly than dialysis. Therefore, from almost all
vantage points, transplantation is the best treatment for
ESRD patients1
.
The growing disparity between the number of patients on
the waiting list for a kidney transplant and the number
of deceased donors has compelled transplant programs to
seek ways to increase the number of organs available for
transplantation2
. Live donor renal transplantation repre-
sents the most promising solution for decreasing the gap
between organ supply and demand. Live donors are now
an increasing source of kidney transplants. Living donor
kidney transplantation is an attractive option for patients
with ESRD. It results in superior patient and graft survival
while the risks for the donor are minimal3,4
.
Unfortunately, many patients with willing live donors will
be excluded from live donor renal transplantation due
to blood type incompatibility or positive donor-specific
crossmatch. Major blood group incompatibility and a posi-
tive T-cell crossmatch have long been considered absolute
contraindications to renal transplantation1
.
Rapaport formulated the principle of paired exchange in
1986, giving it the name “kidney paired donation” (KPD)5
.
He envisaged a process involving two otherwise incompat-
ible donor-recipient pairs, treated at separate transplant
centres simultaneously, with an immediate exchange of
two kidneys to produce two compatible pairs6
. Within
26 B. A Lima et al.
paired donation, there are two forms of kidney exchange:
conventional and unconventional donation. A conven-
tional paired donation describes a situation in which two
donor/recipient pairs who are blood type-incompatible
exchange donors to produce compatible transplants. An
unconventional paired donation applies to donor-recipient
pairs who are incompatible due to positive crossmatch.
Individuals who are unable to donate a kidney to a loved
one due to immunologic incompatibility are exchanged in
order to form compatible pairs; the volunteers thus become
living donors for unknown recipients1
. Kidney exchanges
provide an opportunity for living donor renal transplanta-
tion to patients who have an immunologically incompat-
ible but otherwise suitable donor2
. KPD is emerging as a vi-
able modality for transplanting patients with incompatible
living donors by matching them to pairs with reciprocal
incompatibilities7
. This process has been adopted in several
countries and regions with established live kidney donor
programs to augment available options for patients with
incompatible donors3,4,8,9,10,11,12,13,14
.
The advantages of a paired exchange program are 1) an
increase in the number of kidneys available for transplanta-
tion, 2) avoidance of the risks and costs of desensitisation
strategies designed to remove antidonor antibodies (thus
permitting transplantation despite ABO incompatibility),
and 3) provision of living donor grafts, which are usu-
ally superior to those from deceased donors1
. There are,
however, disadvantages to such a program. First, since
donors participating in paired donation often travel to the
recipient’s transplant centre for donation, they may have
to pay additional travel costs and recover at an unfamiliar
transplant centre. Second, reluctant potential donors who
are afraid of publicly expressing their desire not to donate
cannot use a medical excuse to opt out of donation15
.
Studies have shown that the survival of kidneys trans-
planted from genetically unrelated living donors is similar
to that for kidneys transplanted from haploidentical living
related donors and superior to that for better matched
grafts from deceased donors1,16,17,18
. Patient and graft sur-
vival from paired donation were described as equivalent to
matched direct live donor transplants16,17,19
.
The organ donation policy in Portugal has recently
changed. Previously, candidates for donation could be
third-degree related donors or closer. Since June, 2007
(Law No. 22/2007), all people can be kidney donors with
the usual exceptions (minors and the mentally disturbed).
This allowed for the implementation of a Portuguese KPD
program that will begin at the end of summer 2009. This
program could offer the best transplant option for many
patients with incompatible live donors and could substan-
tially expand the donor pool if fully used in Portugal.
Paired donation can be used for exchange programs that
involve several participating transplant centres. This will
be done by having the match program administered and
executed at a central location.
Portugal has a population of 10 million inhabitants. In
2008, 475 kidney transplants from deceased donors were
performed. In addition to transplants from deceased do-
nors, 49 kidneys from live donors were transplanted during
2008. Although Portugal was, in 2008, the third most ac-
tive country in Europe in terms of donors per million in-
habitants (26.7 donors), less than 10% of all of the kidney
transplants were performed with living donors20
.
In 2008, there were more than 2300 patients wait-listed
for kidney transplantation from deceased donors. Living
donation by family or friends offers an opportunity to
reduce this long waiting list, but ABO incompatibility
or donor-specific sensitisation reduces the number of po-
tential living donors. Crossover transplantation programs
offer an answer when a donor cannot give a kidney to the
intended recipient.
The aim of this study is to describe the algorithm for the
Portuguese KPD program that will begin in 2009.
Materials and Methods
The northern Portugal registry is one of the three (North,
Central and South) regional registries in Portugal that
handle the national transplantation waiting list for kidney
allocation. It is composed of two transplantation centres
and one histocompatibility laboratory. On 1st
April 2009
there were five patients with an incompatible blood type
living donor and eight patients with a positive crossmatch
living donor (one of the latter recipients has four positive
crossmatch living donors) in the northern registry. Four of
the incompatible donors were mothers, eight were siblings,
one was a daughter, two were husbands and the other was
a wife. The characteristics of the 13 recipients (seven male
and six female) were as follows: median age, 35 (range 24
to 58) years; median waiting time, 20 months (range 0 to
72); all recipients in the blood type incompatible group
have 0% for panel-reactive antibodies (PRA) and in the
positive crossmatch group median PRA was 36% (range
0% to 70%). Seven of these recipients are ABO blood type
O, five blood type A and one blood type AB.
Data from incompatible donor-recipient pairs including
age, blood type, human leukocyte antigens (HLA) from
donor and recipient, unacceptable HLA antigens for the
recipient, PRA percentage peak, and waiting time for trans-
plantation were collected from the northern histocompat-
ibility laboratory registries.
Patients awaiting renal transplantation are tested every
three months to ascertain the level and specificity of their
HLA antibodies using complement-dependent microlym-
phocytotoxicity (CDC) tests and flow cytometry with Flow
The Portuguese match algorithm in the kidney paired donation program 27
PRA Class I and II Screening Beads21
, as part of a national
pre-transplant protocol. All patients and donors were mo-
lecularly typed for HLA-A, -B and -DRB1.
All recipient-donor pairs undergo rigorous multilevel
counselling at every stage regarding the benefits, risks and
possible adverse outcomes of kidney donation and trans-
plantation. All patients and donors gave their informed
consent prior to inclusion in the study. There is a require-
ment for strict anonymity between pairs involved in the
proposed exchange.
We used a computer match program by Kaplan et al.2
for
paired and unconventional kidney exchanges. This match
program suggests all of the exchange possibilities involving
two and three donor/recipient incompatible pairs for each
one of the incompatible pairs in our sample. The computer
takes into account ABO and HLA compatibility to define
the possible exchanges.
We define Pi = Pi,i = (Di, Ri) with i ∈ {1, …., n} as an
incompatible ABO blood type or a crossmatch positive
donor/recipient pair.
A two-way exchange between two incompatible pairs is
defined as Pi – Pj with i ≠ j and i, j ∈ {1, …, n} from
which we obtain Pi,j and Pj,i two ABO blood type compat-
ible donor/recipient pairs without known alloantibodies
against the donor. In the two-way exchange recipient, Rj
is paired with donor Di and recipient Ri is paired with
donor Dj.
A three-way exchange between three incompatible donor/
recipient pairs is defined as Pi – Pj – Pk with i ≠ j ≠ k and
i, j, k ∈ {1, …, n}, from which we obtain Pi,j , Pj,k and
Pk,i, three ABO blood type compatible donor/recipient
pairs without known alloantibodies against the donor. In
a three-way exchange, recipient Rj is paired with donor Di,
recipient Rk is paired with donor Dj, while recipient Ri is
paired with donor Dk.
An algorithm based on the Edmonds algorithm from graph
theory22
suggests all of the possible matches and maxim-
ises the number of possible transplants. Combinations
of donors and recipients are matched so that the largest
number of possible matches are made, and priority is given
to O recipients receiving O donors’ kidneys, and then to
the highest average match scores between pairs computed
according to Table 1 point system23
. The described point
system was created for the Portuguese legal allocation pro-
gram for kidneys from deceased donors. This program was
implemented with the intention of distributing donated
kidneys as equitably as possible, based on medical criteria.
The same principles of equity are sought for the KPD
algorithm, leading us to use this point system as match
criteria. The principle that all patients are equal and that
these organs should be accessible to everyone is difficult
to implement. However, these developed systems are an
attempt to be as equitable as possible in the distribution of
donated organs.
Our match algorithm selects exchange combinations with
the following hierarchy: 1) the combinations offer the
maximum number of matched pairs; 2) blood type O
donors preferentially donate to blood type O recipients;
3) pairs have the highest possible donor-recipient average
match scores.
Results
With our 13 incompatible pairs (Pi = (Ri, Di), with i ∈ {1,
…., 13}) it was possible to define three two-way exchanges
or two three-way exchanges, either resulting in six pos-
sible transplants (Figure 1). Combining those exchanges
we obtained a maximised set of seven possible transplants
including two two-way exchanges and one three-way
exchange, taking into account ABO blood type and unac-
ceptable HLA antigens (Figure 2). The selected exchanges
were P1 – P3 , P4 – P12 and P8 – P10 – P13, which resulted
TABLE 1. Scores for the new donor/recipient pair
proposed by Portuguese legislation
criteria points
HLA mismatches:
A) no mismatches HLA-A, -B and -DR (full house) 12
B) no mismatches HLA-B and -DR 8
C) one mismatch HLA-B or -DR 4
D) one mismatch HLA-B and one -DR 2
E) more than two mismatches HLA-B and -DR 1
Sensibilisation:
PRA ≥ 80% 8
PRA ≥ 50% 4
Time on dialysis:
each month 0.1
Age:
< 11 years old 5
between 11 and 18 years old 4
Second transplant:
each month since restarting dialysis 0.1
Age differences between donor and recipient
donor > 60 years old - recipient < 55 years old 0
donor < 40 years old - recipient > 55 years old 0
all other groups 4
In each possible pair exchange two match scores (points’ sum
for the criteria) are computed, the average for these scores
gives the exchange score
28 B. A Lima et al.
matched with both D10 and D13 donors and both R10 and
R13 recipients could be matched with donor D8. Because all
donors and recipients were blood type O, in order to select
one two-way exchange we had to compute the average
score for the two possible donor/recipient pairs, as shown
in Table 3.
In this case, recipient R8 was matched with the donor of
recipient R10 (average score = 5.8). If an eventual positive
crossmatch for this new donor/recipient pair is achieved,
patient R8 could be matched with the donor of patient R13.
in seven ABO blood type compatible donor/recipient pairs
without known alloantibodies against the donors (P1,3,
P3,1, P4,12, P12,4, P8,10, P10,13 and P13,8) as shown in Figure 2.
Table 2 shows the crossmatches to be performed between
the compatible donor/recipient pairs. Within this set of
original donor/recipient pairs, it was not possible to define
exchanges for two blood type A recipients and four blood
type O recipients.
In Figure 1A, which shows the scenario in which only
two-way exchanges were considered, recipient R8 could be
FIGURE 1 - Graph theory model of incompatible donor/recipient nodes, with the arrows representing possible donor/recipient transplants.
Each node represents an incompatible donor/recipient pair (Pi = (Di, Ri)). A gives the representation when only 2-way exchanges are al-
lowed. P1 can be matched with P12 and P3; P12 can be matched with P1, P3 and P4; P8 can be matched with P10 and P13. B shows the possibilities
when only 3-exchanges are allowed. The possibilities are: P1-P3-P12; P1-P12-P3; P3-P4- P12; and P8-P10-P13
A
P4
P5
P6
P7
P8
P9
P10
P11
P12
P13
P1
P2 P3
B
P4
P5
P6
P7
P8
P9
P10
P11
P12
P13
P1
P2 P3
FIGURE 2 - Graph theory model of incompatible donor/recipient
nodes, representing the maximised number of possible donor/recipi-
ent transplants.
Each node represents an incompatible donor/recipient pair (Pi =
(Di, Ri)). The figure represents two 2-way exchanges (P1-P3 and
P4-P12) and one 3-way exchange (P8-P10-P13)
P4
P5
P6
P7
P8
P9
P10
P11
P12
P13
P1
P2 P3
TABLE 2. Donor / recipient compatible pairs
D1 D2 D3 D4 D5 D6 D7 D8 D9 D10 D11 D12 D13
R1 – X
R2 –
R3 X –
R4 – X
R5 –
R6 –
R7 –
R8 – X
R9 –
R10 X –
R11 –
R12 X –
R13 X –
X, the row patient is compatible with the donor of the column.
Each X gives a possible transplant and a crossmatch to perform.
The Portuguese match algorithm in the kidney paired donation program 29
mous paired exchange is prohibited. Couples who wish to
undergo crossover kidney transplantation must therefore
socialise prior to transplantation, although according to the
German Medical Council the common fate of two cross-
over pairs creates a solid and close enough relationship to
meet the demands required by law24
.
Blood type O donor kidneys should be preferentially al-
located to blood-type O recipients. Blood type O recipi-
ents with non-O donors have fewer opportunities to find
a suitable exchange donor due to the lower probability
of participation by other recipients with blood type O
donor16
. In the example presented here, we did not have
the opportunity to use this matching criterion. In the
United Kingdom program blood group O donors may
be used only in O recipients14
, while the South Korean
program maximises the transplants for O recipients25
.
In our algorithm, as in the Dutch system8
, we prioritise
blood group O recipients after maximising the number of
possible transplants.
Our algorithm for donor allocation uses a point system im-
plemented in the Portuguese allocation program of kidneys
from deceased donors. This system takes into account both
recipient and donor characteristics (i.e., HLA mismatches,
also considered in the UK, South Korean and Romanian
systems11,14,25
, and age differences between donor and re-
cipient) rather than only the recipient’s match probability,
as in the Dutch algorithm3,26
. Our punctuation system also
provides solutions in situations that the MP cannot re-
solve. In Figure 2B, if we considered just the incompatible
pairs P1, P3 and P12, we could define two possible 3-way
exchanges (P1 – P3 – P12 and P1 – P12 – P3). In this
example the MP from the Dutch algorithm cannot help us
decide which three-way exchange we should choose, nor
what crossmatches should be performed as both exchanges
have the same MP values and the same waiting time in di-
alysis for the recipients. Our point system gives us different
results for each one of the exchanges.
Specific donor requirements should be defined upfront
consensually by transplant centers as a guarantee for
exchange acceptance after computer matching. After a
medical work-up of the donor, a psychosocial evaluation
must be performed and feelings, expectations and donor
motivations must be determined in order to identify hid-
den unwillingness to donate a kidney.
In the methodology of the Dutch living donor kidney ex-
change program,3
selection among two two-way exchanges
takes place according to match probability (MP)8
. This
criterion is used to ensure that the recipient with the small-
est chance of finding a compatible donor in the pool will be
ranked first. In our example, MP for recipient R10 is 0.24
and MP for R13 is 0.63. So the selected exchange will be
between R8 and R10, (the same pair selected with the score
averaging method).
In Figure 1B, where only three-way exchanges were consid-
ered, to select one three-way exchange from three possibili-
ties we computed the average score for each (Table 4). The
selected three-way exchange was composed of recipients
R3, R12 and R4, with an average score of 10.5. Using the
MP criterion, we calculated an MP of 0.19 for R1, and an
MP for R4 of 0.07. In this case again, the selected three-way
exchange using the Dutch methodology will be the same as
the one selected with the average score method.
Transplant impediments after donors’ assignment with this
algorithm are unlikely, as each patient’s HLA antibodies
have already been identified (and so taken into account in
the matching process) as part of the protocol for registra-
tion on the national list for kidney transplantation from
deceased donors.
Discussion
It is difficult to ensure equal quality of kidneys among
exchange donor pairs in clinical practice. Therefore, it
may be important to maintain anonymity. Some authors
claim that anonymity should be maintained for each ex-
change donor/recipient pair because there is the possibility
of anger or frustration if one recipient or donor does not
fare as well as another16
. In Germany, however, anony-
TABLE 3. Scores for the new donor / recipient pairs in
2-way exchanges
Donor Recipient Score Donor Recipient Score
Average
score
D10 R8 5 D8 R10 6.5 5.8
D13 R8 5 D8 R13 5.8 5.4
TABLE 4. Scores for the new donor / recipient pairs in 3-way exchanges
Donor Recipient Score Donor Recipient Score Donor Recipient Score
Average
score
D3 R1 15,9 D12 R3 11,7 D1 R12 2.6 10.1
D12 R1 15,9 D3 R12 8,6 D1 R3 6.6 10.4
D12 R3 11,7 D3 R4 14.1 D4 R12 5.6 10.5
30 B. A Lima et al.
triplets. Theoretically, quartets, quintets, sextets, and so
on will help even more patients, but these solutions are
logistically more difficult to realise31
. For that reason we
recommend limiting this kind of program to triple (three-
way) exchanges, at least until logistics have been success-
fully established.
The results presented here were achieved using a sample
from northern Portugal, a Portuguese region that repre-
sents approximately one third of the country’s area and has
one of the three regional registries for kidney allocation
in Portugal. The algorithm proposed here, when applied
nationally, will likely have even better results. As described
by others, opportunities for transplantation are propor-
tional to the number of donors and patients willing to be
considered for an exchange2
. In our example and using our
algorithm, we were able to define seven possible transplants
from a pool of 13 incompatible donor/recipient pairs.
Despite the potential of KPD, it is not practised widely
throughout the world, partly due to the complexity of do-
nor allocation in the exchange, logistic barriers, and lack of
a standardised protocol4
. Portugal, due to its geographical
dimensions (about 100,000 Km2), is a suitable candidate
for the implementation of such a program.
A shortage remains of kidneys for transplantation from
deceased donors in spite of many initiatives to expand
the donor pool6
. Increasing the number of living donors
should be a concern for those with responsibilities in organ
allocation; the use of unrelated live donors has the greatest
potential for increasing the availability of kidneys.
Demographic evolution in developed countries has re-
duced the number of children per family, limiting possible
genetically related donors for many patients. Now there
are more prospective voluntary kidney donors among
spouses, distant relatives, and friends. The greatest advan-
tage of KPD is in ensuring the continued participation of
a number of suitable, motivated living donors who would
otherwise be lost to the live donation program by virtue of
an incompatibility with their intended recipient6
.
In the Netherlands, seven transplant centres embarked on a
kidney exchange program in 2004 according to a common
protocol3
. Their procedure has five steps: 1) registration,
2) computerised matching, 3) crossmatching, 4) accept-
ance of the exchange donors by transplant centres, and 5)
transplantation26
. The Portuguese program is quite similar
to the Dutch protocol - the major difference is in our pro-
posal for computer matching.
Paired living donor kidney exchange is an excellent so-
lution and the first choice for a substantial number of
recipients who cannot identify a compatible donor due
to an ABO blood type or crossmatch incompatibility32
.
Allowing compatible pairs to participate in KPD were
previously proposed as a way to achieve a larger number
of matches for all pairs7
.
Barriers to this kind of program can be avoided by care-
fully defining non-acceptable HLA mismatches and
carefully selecting donors and recipients before each
match run. Hurdles can be overcome within a flexible
organisation, one able to create alternative solutions when
problems arise. Centralised allocation and crossmatch
procedures are instrumental to this flexibility26,27
. In our
example, we have eight recipients with positive donor
crossmatch in the initial pool. For these, we were able
to identify their alloantibodies and therefore eliminate
potential donors with specific HLA antigens and avoid
future positive crossmatches.
A national pool offers the possibility of a greater number of
matches. However, this would require the donor or recipi-
ent of each incompatible pair to receive the transplant at
the same hospital as the matched partner or that kidneys be
transported between institutions. The Dutch exchange pro-
gram3
requires the donor to travel to the recipient centre.
With this, ischemia time and logistic problems are mini-
mised and it is especially the recipient who benefits from
his/her donor’s travel. Surgeons are also more sympathetic
to this solution rather than shipment of kidneys28
. Rapa-
port5
originally proposed that KPD operations should be
conducted simultaneously, so that both procedures could
be aborted if a complication arose in one individual6
.
The requirement of the donor travelling large distances is
likely to be the principal deterrent for this kind of program;
it separates families, creates anxiety and incurs costs to the
family. A solution to this problem was proposed by Waki
and Terasaki28
: shipment of the donor kidney. Data pre-
sented in a previous study29
suggested that organ transport
with cold ischemia time less than 8 hours does not differ
from live donor kidney transplantation. This solution does
not resolve potential complications during transplantation,
such as an unsuitable kidney for transplantation or an un-
suitable recipient for the graft. Portugal’s geographical area
is not comparable to the United States (in Portugal, the two
most distant transplant units require three and a half hours
travel time between them). While large distances are likely
to be the primary issue for the implementation of such a
system in the United States, in Portugal this can be solved
via donor travel to the recipient’s hospital if the donors are
fully informed and concerned about the importance of this
transplant. As previously described in a Portuguese study30
,
living donors providing direct donation showed positive
perceptions about donation, did not regret their decision,
and strongly recommend it to others.
As in the Dutch program27
we intended to keep matching
criteria simple. So we did not take into account donor age,
sex, CMV sera status, renal function or the number of
HLA mismatches in our transplantation algorithm.
More transplant possibilities can be created when ex-
changes between three pairs are considered, i.e., so-called
The Portuguese match algorithm in the kidney paired donation program 31
References
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Montgomery R., Zachary A., Ratner L., et al.: Clinical results from
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Rapaport F.T.: The case for a living emotionally related interna-
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Demonico F., Morrisey P., Lipowitz G., et al.: Donor kidney ex-
changes. Am J Transplant, 4, 1628-1634, 2004.
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Basu G., Daniel D., Rajagopal A., et al.: A model for Human
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Lucan M.: Five years of single-center experience with paired
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Kranenburg L., Visak T., Weimar W., et al.: Starting a Crosso-
ver kidney transplantation program in the Netherlands: ethical
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Hanto R., Reistma W., Delmonico F.: The development of a suc-
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Johnson R., Allen J., Fuggle S., et al.: Early experience of paired
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Waterman A., Schenk E., Barret A., et al.: Incompatible kidney
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Huh K., Kim M., Ju M., et al.: Exchange living-donor kidney trans-
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Park K., Lee J., Huh K., et al.: Exchange living-donor kidney trans-
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Paired donation remains a rapidly developing field as a
result of ethical, scientific, and clinical innovations and
development. Despite this growth, paired donation has
not realised its potential. However, several paired donation
programs in the US, Europe, and Asia are established and
actively recruiting patients33
.
The major advantages of a donor exchange are that, after
arrangements are made and consent obtained, an uncom-
plicated ABO-compatible transplant is performed under
standard immunosuppression with excellent results. Ex-
pensive interventions such as intravenous immunoglobulin
and plasmapheresis associated with unpredictable rates of
biological graft loss34
are avoided. In addition, previously
unusable kidneys can be exploited; allowing patients with
ESRD to be removed from the waiting list, the benefit
not only accrues for the recipient, but also for the patients
remaining on the list17
.
Several issues have been identified regarding KPD: the
influence of “donation by strangers” on the motivation
and willingness of donor-patient couples, the issue of
anonymity, the loss of the possibility of “medical excuses”
for unwilling donors, the view that crossover is a first step
to commercial organ donation, and the interference with
existing organ donation programs. Earlier efforts suggest
that none of these issues, separately or combined, seem to
impede the efficient organisation of a crossover program or
raise worrying ethical issues12
.
Conclusions
Simulations suggest that the most cost-effective modality
for transplanting incompatible donor-recipient pairs is a
national KPD program utilising an optimised matching
algorithm35
. Almost all patients who would benefit from
list paired donation are predicted to be better served by a
national KPD program. With this evidence, and reports
of excellent clinical outcomes from KPD, planning for a
national KPD program should be a priority for the trans-
plantation community36
.
KPD programs can be successful, but relatively high
numbers of candidates are needed, and thus cooperation
between centres and trust among them is essential27
.
In conclusion, the national KPD Portuguese program
soon to be realised, may prevent the current loss of a
significant number of suitable living donors, and thereby
have a significant impact on the acute shortage of organs
for transplantation in addition to the existing Portuguese
live donor kidney transplant and deceased donor trans-
plant programs. The described algorithm will help to en-
sure an allocation program as equitable as possible based
on medical criteria without compromising the number of
potential transplants.
32 B. A Lima et al.
29
Simpkins C., Montgomery R., Hawxby A., et al.: Cold ischemia
time and allograft outcomes in live donor renal transplantation: Is
live donor organ transport deasible? Am J Transplant, 7, 99-107,
2007.
30
Frade I.C., Fonseca I., Dias L., et al.: Impact assessment in living
kidney donation: psychosocial aspects in the donor. Transplant
Proc, 40, 677-681, 2008.
31
Klerk M., Haase-Kromwijk B., Claas F., et al.: Living donor kidney
exchange for both ABO-incompatible and crossmatch positive
donor-recipient combinations. Transplant Proc, 38, 2793-2795,
2006.
32
Klerk M., Witvliet M., Haase-Kromwijk B., et al.: A highly efficient
living donor kidney exchange program for both blood type and
crossmatch incompatible donor-recipient combinations. Transplan-
tation, 82, 1616-1620, 2006.
33
Woodle S., Goldfarb D., Segev D., et al.: Kidney paired donation:
state of the science and practice. Curr Opin Organ Transplant, 12,
384-389, 2007.
34
Delmonico F.: Council of the Transplantation Society. A Report of
the Amsterdam Forum On the Care of the Live Kidney Donor: Data
and Medical Guidelines. Transplantation, 79 (6 Suppl), S53-66,
2005.
35
Segev D., Gentry S., Warren D., et al.: Kidney donation and
optimizing the use of live donor organs. JAMA, 293, 1883-1890,
2005.
36
Segev D., Gentry S., Keith J., et al.: Characterization of waiting
times in a simulation of kidney paired donation. Am J Transplant,
5, 2448-2455, 2005.
18
Manauis M., Pilar K., Lesaca R., et al.: A national program for
nondirected kidney donation from living unrelated donors: the
Philippine experience. Transplant Proc, 40, 2100-2103, 2008.
19
Segev D., Kucirka L., Gentry S., et al.: Utilization and outcomes
of kidney paired donation in the United States. Transplantation,
86, 502-510, 2008.
20
Actividade de Colheita e transplantes. Relatório Estatístico. Au-
toridade para os Serviços de Sangue e Transplantação, 2008.
21
Magee B., Martin J., Middleton D.: The repercussions of im-
plementing flow cytometry as a single HLA antibody screening
technique in prospective renal transplant recipients. Transplant
International, 19, 105-109, 2009.
22
Edmonds J.: Paths, trees and flowers. Can J Math, 17, 449,
1965.
23
Despacho nº 6537/2007; Diário da República, 2ª série – Nº66 – 3
de Abril de 2007.
24
Rittner C., Besold A., Wandel E.: A proposal for an anonymous liv-
ing organ donation in Germany. Legal Medicine, 5, S68-S71, 2003.
25
Kim B.S., Kim Y.S., Kim S.I., et al.: Outcome of multipair donor
kidney exchange by a web-based algorithm. J Am Soc Nephrol,
18, 1000, 2007.
26
Klerk M., Witvliet M., Haase-Kromwijk B., et al.: Hurdles, barriers,
and successes of a national living donor kidney exchange program.
Transplantation, 86, 1749-1753, 2008.
27
Klerk M., Weimar W.: Ingredients for a successful living donor
kidney exchange program. Transplantation, 86, 511-512, 2008.
28
Waki K., Terasaki P.I.: Paired kidney donation by shipment of liv-
ing donor kidneys. Clin Transplant, 21, 186-191, 2007.

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OTC - Lima, 2010

  • 1. 25 THE PORTUGUESE MATCH ALGORITHM IN THE KIDNEY PAIRED DONATION PROGRAM Bruno A. Lima1 , Leonídio Dias2 , António C. Henriques2 , Helena Alves1 1 Centro de Histocompatibilidade do Norte, Porto, Portugal 2 Serviço de Nefrologia, Centro Hospitalar do Porto, Hospital de Sto António, Porto, Portugal Keywords - Kidney paired donation, kidney transplantation, live donation, match algorithm Summary - The growing disparity between the number of patients on the national list waiting for a kidney transplant and the number of deceased donors has compelled transplant programs to seek ways to increase the number of organs available for transplantation. Rapaport formulated the principle of paired exchange in 1986, giving it the title “kidney paired donation” (KPD). Individuals who are unable to donate a kidney to a loved one due to immunologic incompatibility are exchanged in order to form compatible pairs; the volunteers thus become living donors for unknown recipients. The aim of this study is to describe the algorithm for the Portuguese KPD program that will being in 2009. Data were used from five patients with an incompatible blood type living donor and eight patients, each with a positive crossmatch living donor; one of the latter recipients had four positive crossmatch living donors. We present a computer match that selects exchange combinations with the following hierarchy: 1) maximum number of matched pairs; 2) blood type O recipients are given priority in receiving from blood type O donors; 3) pairs with a higher donor/recipient average match score. With a sample of thirteen incompatible donor/recipients pairs, we were able to define seven possible transplants. The algorithm described helped to ensure an allocation program that was as equitable as possible based on medical criteria without compromising the possible number of transplants. ORGANS, TISSUES & CELLS, (13), 25-32, 2010 Mailing address: Bruno A Lima, Centro de Histocompatibilidade do Norte, Rua Dr Roberto Frias, 4200-467 Porto, Portugal; e-mail: bruno@chnorte.min-saude.pt Introduction Kidney transplantation improves and extends the lives of patients with end-stage renal disease (ESRD). Transplanta- tion is less costly than dialysis. Therefore, from almost all vantage points, transplantation is the best treatment for ESRD patients1 . The growing disparity between the number of patients on the waiting list for a kidney transplant and the number of deceased donors has compelled transplant programs to seek ways to increase the number of organs available for transplantation2 . Live donor renal transplantation repre- sents the most promising solution for decreasing the gap between organ supply and demand. Live donors are now an increasing source of kidney transplants. Living donor kidney transplantation is an attractive option for patients with ESRD. It results in superior patient and graft survival while the risks for the donor are minimal3,4 . Unfortunately, many patients with willing live donors will be excluded from live donor renal transplantation due to blood type incompatibility or positive donor-specific crossmatch. Major blood group incompatibility and a posi- tive T-cell crossmatch have long been considered absolute contraindications to renal transplantation1 . Rapaport formulated the principle of paired exchange in 1986, giving it the name “kidney paired donation” (KPD)5 . He envisaged a process involving two otherwise incompat- ible donor-recipient pairs, treated at separate transplant centres simultaneously, with an immediate exchange of two kidneys to produce two compatible pairs6 . Within
  • 2. 26 B. A Lima et al. paired donation, there are two forms of kidney exchange: conventional and unconventional donation. A conven- tional paired donation describes a situation in which two donor/recipient pairs who are blood type-incompatible exchange donors to produce compatible transplants. An unconventional paired donation applies to donor-recipient pairs who are incompatible due to positive crossmatch. Individuals who are unable to donate a kidney to a loved one due to immunologic incompatibility are exchanged in order to form compatible pairs; the volunteers thus become living donors for unknown recipients1 . Kidney exchanges provide an opportunity for living donor renal transplanta- tion to patients who have an immunologically incompat- ible but otherwise suitable donor2 . KPD is emerging as a vi- able modality for transplanting patients with incompatible living donors by matching them to pairs with reciprocal incompatibilities7 . This process has been adopted in several countries and regions with established live kidney donor programs to augment available options for patients with incompatible donors3,4,8,9,10,11,12,13,14 . The advantages of a paired exchange program are 1) an increase in the number of kidneys available for transplanta- tion, 2) avoidance of the risks and costs of desensitisation strategies designed to remove antidonor antibodies (thus permitting transplantation despite ABO incompatibility), and 3) provision of living donor grafts, which are usu- ally superior to those from deceased donors1 . There are, however, disadvantages to such a program. First, since donors participating in paired donation often travel to the recipient’s transplant centre for donation, they may have to pay additional travel costs and recover at an unfamiliar transplant centre. Second, reluctant potential donors who are afraid of publicly expressing their desire not to donate cannot use a medical excuse to opt out of donation15 . Studies have shown that the survival of kidneys trans- planted from genetically unrelated living donors is similar to that for kidneys transplanted from haploidentical living related donors and superior to that for better matched grafts from deceased donors1,16,17,18 . Patient and graft sur- vival from paired donation were described as equivalent to matched direct live donor transplants16,17,19 . The organ donation policy in Portugal has recently changed. Previously, candidates for donation could be third-degree related donors or closer. Since June, 2007 (Law No. 22/2007), all people can be kidney donors with the usual exceptions (minors and the mentally disturbed). This allowed for the implementation of a Portuguese KPD program that will begin at the end of summer 2009. This program could offer the best transplant option for many patients with incompatible live donors and could substan- tially expand the donor pool if fully used in Portugal. Paired donation can be used for exchange programs that involve several participating transplant centres. This will be done by having the match program administered and executed at a central location. Portugal has a population of 10 million inhabitants. In 2008, 475 kidney transplants from deceased donors were performed. In addition to transplants from deceased do- nors, 49 kidneys from live donors were transplanted during 2008. Although Portugal was, in 2008, the third most ac- tive country in Europe in terms of donors per million in- habitants (26.7 donors), less than 10% of all of the kidney transplants were performed with living donors20 . In 2008, there were more than 2300 patients wait-listed for kidney transplantation from deceased donors. Living donation by family or friends offers an opportunity to reduce this long waiting list, but ABO incompatibility or donor-specific sensitisation reduces the number of po- tential living donors. Crossover transplantation programs offer an answer when a donor cannot give a kidney to the intended recipient. The aim of this study is to describe the algorithm for the Portuguese KPD program that will begin in 2009. Materials and Methods The northern Portugal registry is one of the three (North, Central and South) regional registries in Portugal that handle the national transplantation waiting list for kidney allocation. It is composed of two transplantation centres and one histocompatibility laboratory. On 1st April 2009 there were five patients with an incompatible blood type living donor and eight patients with a positive crossmatch living donor (one of the latter recipients has four positive crossmatch living donors) in the northern registry. Four of the incompatible donors were mothers, eight were siblings, one was a daughter, two were husbands and the other was a wife. The characteristics of the 13 recipients (seven male and six female) were as follows: median age, 35 (range 24 to 58) years; median waiting time, 20 months (range 0 to 72); all recipients in the blood type incompatible group have 0% for panel-reactive antibodies (PRA) and in the positive crossmatch group median PRA was 36% (range 0% to 70%). Seven of these recipients are ABO blood type O, five blood type A and one blood type AB. Data from incompatible donor-recipient pairs including age, blood type, human leukocyte antigens (HLA) from donor and recipient, unacceptable HLA antigens for the recipient, PRA percentage peak, and waiting time for trans- plantation were collected from the northern histocompat- ibility laboratory registries. Patients awaiting renal transplantation are tested every three months to ascertain the level and specificity of their HLA antibodies using complement-dependent microlym- phocytotoxicity (CDC) tests and flow cytometry with Flow
  • 3. The Portuguese match algorithm in the kidney paired donation program 27 PRA Class I and II Screening Beads21 , as part of a national pre-transplant protocol. All patients and donors were mo- lecularly typed for HLA-A, -B and -DRB1. All recipient-donor pairs undergo rigorous multilevel counselling at every stage regarding the benefits, risks and possible adverse outcomes of kidney donation and trans- plantation. All patients and donors gave their informed consent prior to inclusion in the study. There is a require- ment for strict anonymity between pairs involved in the proposed exchange. We used a computer match program by Kaplan et al.2 for paired and unconventional kidney exchanges. This match program suggests all of the exchange possibilities involving two and three donor/recipient incompatible pairs for each one of the incompatible pairs in our sample. The computer takes into account ABO and HLA compatibility to define the possible exchanges. We define Pi = Pi,i = (Di, Ri) with i ∈ {1, …., n} as an incompatible ABO blood type or a crossmatch positive donor/recipient pair. A two-way exchange between two incompatible pairs is defined as Pi – Pj with i ≠ j and i, j ∈ {1, …, n} from which we obtain Pi,j and Pj,i two ABO blood type compat- ible donor/recipient pairs without known alloantibodies against the donor. In the two-way exchange recipient, Rj is paired with donor Di and recipient Ri is paired with donor Dj. A three-way exchange between three incompatible donor/ recipient pairs is defined as Pi – Pj – Pk with i ≠ j ≠ k and i, j, k ∈ {1, …, n}, from which we obtain Pi,j , Pj,k and Pk,i, three ABO blood type compatible donor/recipient pairs without known alloantibodies against the donor. In a three-way exchange, recipient Rj is paired with donor Di, recipient Rk is paired with donor Dj, while recipient Ri is paired with donor Dk. An algorithm based on the Edmonds algorithm from graph theory22 suggests all of the possible matches and maxim- ises the number of possible transplants. Combinations of donors and recipients are matched so that the largest number of possible matches are made, and priority is given to O recipients receiving O donors’ kidneys, and then to the highest average match scores between pairs computed according to Table 1 point system23 . The described point system was created for the Portuguese legal allocation pro- gram for kidneys from deceased donors. This program was implemented with the intention of distributing donated kidneys as equitably as possible, based on medical criteria. The same principles of equity are sought for the KPD algorithm, leading us to use this point system as match criteria. The principle that all patients are equal and that these organs should be accessible to everyone is difficult to implement. However, these developed systems are an attempt to be as equitable as possible in the distribution of donated organs. Our match algorithm selects exchange combinations with the following hierarchy: 1) the combinations offer the maximum number of matched pairs; 2) blood type O donors preferentially donate to blood type O recipients; 3) pairs have the highest possible donor-recipient average match scores. Results With our 13 incompatible pairs (Pi = (Ri, Di), with i ∈ {1, …., 13}) it was possible to define three two-way exchanges or two three-way exchanges, either resulting in six pos- sible transplants (Figure 1). Combining those exchanges we obtained a maximised set of seven possible transplants including two two-way exchanges and one three-way exchange, taking into account ABO blood type and unac- ceptable HLA antigens (Figure 2). The selected exchanges were P1 – P3 , P4 – P12 and P8 – P10 – P13, which resulted TABLE 1. Scores for the new donor/recipient pair proposed by Portuguese legislation criteria points HLA mismatches: A) no mismatches HLA-A, -B and -DR (full house) 12 B) no mismatches HLA-B and -DR 8 C) one mismatch HLA-B or -DR 4 D) one mismatch HLA-B and one -DR 2 E) more than two mismatches HLA-B and -DR 1 Sensibilisation: PRA ≥ 80% 8 PRA ≥ 50% 4 Time on dialysis: each month 0.1 Age: < 11 years old 5 between 11 and 18 years old 4 Second transplant: each month since restarting dialysis 0.1 Age differences between donor and recipient donor > 60 years old - recipient < 55 years old 0 donor < 40 years old - recipient > 55 years old 0 all other groups 4 In each possible pair exchange two match scores (points’ sum for the criteria) are computed, the average for these scores gives the exchange score
  • 4. 28 B. A Lima et al. matched with both D10 and D13 donors and both R10 and R13 recipients could be matched with donor D8. Because all donors and recipients were blood type O, in order to select one two-way exchange we had to compute the average score for the two possible donor/recipient pairs, as shown in Table 3. In this case, recipient R8 was matched with the donor of recipient R10 (average score = 5.8). If an eventual positive crossmatch for this new donor/recipient pair is achieved, patient R8 could be matched with the donor of patient R13. in seven ABO blood type compatible donor/recipient pairs without known alloantibodies against the donors (P1,3, P3,1, P4,12, P12,4, P8,10, P10,13 and P13,8) as shown in Figure 2. Table 2 shows the crossmatches to be performed between the compatible donor/recipient pairs. Within this set of original donor/recipient pairs, it was not possible to define exchanges for two blood type A recipients and four blood type O recipients. In Figure 1A, which shows the scenario in which only two-way exchanges were considered, recipient R8 could be FIGURE 1 - Graph theory model of incompatible donor/recipient nodes, with the arrows representing possible donor/recipient transplants. Each node represents an incompatible donor/recipient pair (Pi = (Di, Ri)). A gives the representation when only 2-way exchanges are al- lowed. P1 can be matched with P12 and P3; P12 can be matched with P1, P3 and P4; P8 can be matched with P10 and P13. B shows the possibilities when only 3-exchanges are allowed. The possibilities are: P1-P3-P12; P1-P12-P3; P3-P4- P12; and P8-P10-P13 A P4 P5 P6 P7 P8 P9 P10 P11 P12 P13 P1 P2 P3 B P4 P5 P6 P7 P8 P9 P10 P11 P12 P13 P1 P2 P3 FIGURE 2 - Graph theory model of incompatible donor/recipient nodes, representing the maximised number of possible donor/recipi- ent transplants. Each node represents an incompatible donor/recipient pair (Pi = (Di, Ri)). The figure represents two 2-way exchanges (P1-P3 and P4-P12) and one 3-way exchange (P8-P10-P13) P4 P5 P6 P7 P8 P9 P10 P11 P12 P13 P1 P2 P3 TABLE 2. Donor / recipient compatible pairs D1 D2 D3 D4 D5 D6 D7 D8 D9 D10 D11 D12 D13 R1 – X R2 – R3 X – R4 – X R5 – R6 – R7 – R8 – X R9 – R10 X – R11 – R12 X – R13 X – X, the row patient is compatible with the donor of the column. Each X gives a possible transplant and a crossmatch to perform.
  • 5. The Portuguese match algorithm in the kidney paired donation program 29 mous paired exchange is prohibited. Couples who wish to undergo crossover kidney transplantation must therefore socialise prior to transplantation, although according to the German Medical Council the common fate of two cross- over pairs creates a solid and close enough relationship to meet the demands required by law24 . Blood type O donor kidneys should be preferentially al- located to blood-type O recipients. Blood type O recipi- ents with non-O donors have fewer opportunities to find a suitable exchange donor due to the lower probability of participation by other recipients with blood type O donor16 . In the example presented here, we did not have the opportunity to use this matching criterion. In the United Kingdom program blood group O donors may be used only in O recipients14 , while the South Korean program maximises the transplants for O recipients25 . In our algorithm, as in the Dutch system8 , we prioritise blood group O recipients after maximising the number of possible transplants. Our algorithm for donor allocation uses a point system im- plemented in the Portuguese allocation program of kidneys from deceased donors. This system takes into account both recipient and donor characteristics (i.e., HLA mismatches, also considered in the UK, South Korean and Romanian systems11,14,25 , and age differences between donor and re- cipient) rather than only the recipient’s match probability, as in the Dutch algorithm3,26 . Our punctuation system also provides solutions in situations that the MP cannot re- solve. In Figure 2B, if we considered just the incompatible pairs P1, P3 and P12, we could define two possible 3-way exchanges (P1 – P3 – P12 and P1 – P12 – P3). In this example the MP from the Dutch algorithm cannot help us decide which three-way exchange we should choose, nor what crossmatches should be performed as both exchanges have the same MP values and the same waiting time in di- alysis for the recipients. Our point system gives us different results for each one of the exchanges. Specific donor requirements should be defined upfront consensually by transplant centers as a guarantee for exchange acceptance after computer matching. After a medical work-up of the donor, a psychosocial evaluation must be performed and feelings, expectations and donor motivations must be determined in order to identify hid- den unwillingness to donate a kidney. In the methodology of the Dutch living donor kidney ex- change program,3 selection among two two-way exchanges takes place according to match probability (MP)8 . This criterion is used to ensure that the recipient with the small- est chance of finding a compatible donor in the pool will be ranked first. In our example, MP for recipient R10 is 0.24 and MP for R13 is 0.63. So the selected exchange will be between R8 and R10, (the same pair selected with the score averaging method). In Figure 1B, where only three-way exchanges were consid- ered, to select one three-way exchange from three possibili- ties we computed the average score for each (Table 4). The selected three-way exchange was composed of recipients R3, R12 and R4, with an average score of 10.5. Using the MP criterion, we calculated an MP of 0.19 for R1, and an MP for R4 of 0.07. In this case again, the selected three-way exchange using the Dutch methodology will be the same as the one selected with the average score method. Transplant impediments after donors’ assignment with this algorithm are unlikely, as each patient’s HLA antibodies have already been identified (and so taken into account in the matching process) as part of the protocol for registra- tion on the national list for kidney transplantation from deceased donors. Discussion It is difficult to ensure equal quality of kidneys among exchange donor pairs in clinical practice. Therefore, it may be important to maintain anonymity. Some authors claim that anonymity should be maintained for each ex- change donor/recipient pair because there is the possibility of anger or frustration if one recipient or donor does not fare as well as another16 . In Germany, however, anony- TABLE 3. Scores for the new donor / recipient pairs in 2-way exchanges Donor Recipient Score Donor Recipient Score Average score D10 R8 5 D8 R10 6.5 5.8 D13 R8 5 D8 R13 5.8 5.4 TABLE 4. Scores for the new donor / recipient pairs in 3-way exchanges Donor Recipient Score Donor Recipient Score Donor Recipient Score Average score D3 R1 15,9 D12 R3 11,7 D1 R12 2.6 10.1 D12 R1 15,9 D3 R12 8,6 D1 R3 6.6 10.4 D12 R3 11,7 D3 R4 14.1 D4 R12 5.6 10.5
  • 6. 30 B. A Lima et al. triplets. Theoretically, quartets, quintets, sextets, and so on will help even more patients, but these solutions are logistically more difficult to realise31 . For that reason we recommend limiting this kind of program to triple (three- way) exchanges, at least until logistics have been success- fully established. The results presented here were achieved using a sample from northern Portugal, a Portuguese region that repre- sents approximately one third of the country’s area and has one of the three regional registries for kidney allocation in Portugal. The algorithm proposed here, when applied nationally, will likely have even better results. As described by others, opportunities for transplantation are propor- tional to the number of donors and patients willing to be considered for an exchange2 . In our example and using our algorithm, we were able to define seven possible transplants from a pool of 13 incompatible donor/recipient pairs. Despite the potential of KPD, it is not practised widely throughout the world, partly due to the complexity of do- nor allocation in the exchange, logistic barriers, and lack of a standardised protocol4 . Portugal, due to its geographical dimensions (about 100,000 Km2), is a suitable candidate for the implementation of such a program. A shortage remains of kidneys for transplantation from deceased donors in spite of many initiatives to expand the donor pool6 . Increasing the number of living donors should be a concern for those with responsibilities in organ allocation; the use of unrelated live donors has the greatest potential for increasing the availability of kidneys. Demographic evolution in developed countries has re- duced the number of children per family, limiting possible genetically related donors for many patients. Now there are more prospective voluntary kidney donors among spouses, distant relatives, and friends. The greatest advan- tage of KPD is in ensuring the continued participation of a number of suitable, motivated living donors who would otherwise be lost to the live donation program by virtue of an incompatibility with their intended recipient6 . In the Netherlands, seven transplant centres embarked on a kidney exchange program in 2004 according to a common protocol3 . Their procedure has five steps: 1) registration, 2) computerised matching, 3) crossmatching, 4) accept- ance of the exchange donors by transplant centres, and 5) transplantation26 . The Portuguese program is quite similar to the Dutch protocol - the major difference is in our pro- posal for computer matching. Paired living donor kidney exchange is an excellent so- lution and the first choice for a substantial number of recipients who cannot identify a compatible donor due to an ABO blood type or crossmatch incompatibility32 . Allowing compatible pairs to participate in KPD were previously proposed as a way to achieve a larger number of matches for all pairs7 . Barriers to this kind of program can be avoided by care- fully defining non-acceptable HLA mismatches and carefully selecting donors and recipients before each match run. Hurdles can be overcome within a flexible organisation, one able to create alternative solutions when problems arise. Centralised allocation and crossmatch procedures are instrumental to this flexibility26,27 . In our example, we have eight recipients with positive donor crossmatch in the initial pool. For these, we were able to identify their alloantibodies and therefore eliminate potential donors with specific HLA antigens and avoid future positive crossmatches. A national pool offers the possibility of a greater number of matches. However, this would require the donor or recipi- ent of each incompatible pair to receive the transplant at the same hospital as the matched partner or that kidneys be transported between institutions. The Dutch exchange pro- gram3 requires the donor to travel to the recipient centre. With this, ischemia time and logistic problems are mini- mised and it is especially the recipient who benefits from his/her donor’s travel. Surgeons are also more sympathetic to this solution rather than shipment of kidneys28 . Rapa- port5 originally proposed that KPD operations should be conducted simultaneously, so that both procedures could be aborted if a complication arose in one individual6 . The requirement of the donor travelling large distances is likely to be the principal deterrent for this kind of program; it separates families, creates anxiety and incurs costs to the family. A solution to this problem was proposed by Waki and Terasaki28 : shipment of the donor kidney. Data pre- sented in a previous study29 suggested that organ transport with cold ischemia time less than 8 hours does not differ from live donor kidney transplantation. This solution does not resolve potential complications during transplantation, such as an unsuitable kidney for transplantation or an un- suitable recipient for the graft. Portugal’s geographical area is not comparable to the United States (in Portugal, the two most distant transplant units require three and a half hours travel time between them). While large distances are likely to be the primary issue for the implementation of such a system in the United States, in Portugal this can be solved via donor travel to the recipient’s hospital if the donors are fully informed and concerned about the importance of this transplant. As previously described in a Portuguese study30 , living donors providing direct donation showed positive perceptions about donation, did not regret their decision, and strongly recommend it to others. As in the Dutch program27 we intended to keep matching criteria simple. So we did not take into account donor age, sex, CMV sera status, renal function or the number of HLA mismatches in our transplantation algorithm. More transplant possibilities can be created when ex- changes between three pairs are considered, i.e., so-called
  • 7. The Portuguese match algorithm in the kidney paired donation program 31 References 1 Spital S.: Increasing the Pool of Transplantable Kidneys Through Unrelated Living Donors and Living Donor Paired Exchange. Semin Dial, 18 (6), 469-473, 2005. 2 Kaplan I., Houp J., Leffell M., Hart J., Zachary A.: A computer match program for paired and unconventional kidney exchanges. Am J Transplant, 5, 2306-2308, 2005. 3 Klerk M., Haase-Kromwijk B., Class F., Weimar W.: Methodology of the Dutch living donor kidney exchange program. Organs, Tis- sues and Cells, 2, 83-86, 2008. 4 Montgomery R., Zachary A., Ratner L., et al.: Clinical results from transplanting incompatible live kidney donor/recipient pairs using kidney paired donation. JAMA, 13, 1655-1663, 2005. 5 Rapaport F.T.: The case for a living emotionally related interna- tional kidney donor exchange registry. Transplant Proc, 18 (Suppl 2), 5-9,1986. 6 Mahendram A., Veitch P.: Paired exchange programmes can expand the live kidney donor pool. British journal of Surgery, 94, 657-664, 2007. 7 Gentry S., Segev D., Simmerling M., Montgomery R.: Expanding kidney Paired donation through participation by compatible pairs. Am J Transplant, 7, 2361-2370, 2007. 8 Keizer K., Klerk M., Haase-Kromwijk B., Weimar W.: The Dutch algorithm in living donor kidney exchange. Transplant Proc, 37, 589-591, 2005. 9 Demonico F., Morrisey P., Lipowitz G., et al.: Donor kidney ex- changes. Am J Transplant, 4, 1628-1634, 2004. 10 Basu G., Daniel D., Rajagopal A., et al.: A model for Human Leukocyte Antigen-Matched donor-swap transplantation in India. Transplantation, 85, 687-692, 2008. 11 Lucan M.: Five years of single-center experience with paired kidney exchange transplantation. Transplant Proc, 39, 1371-1375, 2007. 12 Kranenburg L., Visak T., Weimar W., et al.: Starting a Crosso- ver kidney transplantation program in the Netherlands: ethical and psychological considerations. Transplantation, 78, 194-197, 2004. 13 Hanto R., Reistma W., Delmonico F.: The development of a suc- cessful multiregional kidney paired donation program. Transplanta- tion, 86, 1744-1748, 2008. 14 Johnson R., Allen J., Fuggle S., et al.: Early experience of paired living kidney donation in the United Kingdom. Transplantation, 86, 1672-1677, 2008. 15 Waterman A., Schenk E., Barret A., et al.: Incompatible kidney donor candidates’ willingness to participate in donor-exchange and non-directed donation. Am J Transplant, 6, 1631-1638, 2006. 16 Huh K., Kim M., Ju M., et al.: Exchange living-donor kidney trans- plantation: merits and limitations. Transplantation, 86, 430-435, 2008. 17 Park K., Lee J., Huh K., et al.: Exchange living-donor kidney trans- plantation: diminution of donor organ shortage. Transplant Proc, 36, 2949-2951, 2004. Paired donation remains a rapidly developing field as a result of ethical, scientific, and clinical innovations and development. Despite this growth, paired donation has not realised its potential. However, several paired donation programs in the US, Europe, and Asia are established and actively recruiting patients33 . The major advantages of a donor exchange are that, after arrangements are made and consent obtained, an uncom- plicated ABO-compatible transplant is performed under standard immunosuppression with excellent results. Ex- pensive interventions such as intravenous immunoglobulin and plasmapheresis associated with unpredictable rates of biological graft loss34 are avoided. In addition, previously unusable kidneys can be exploited; allowing patients with ESRD to be removed from the waiting list, the benefit not only accrues for the recipient, but also for the patients remaining on the list17 . Several issues have been identified regarding KPD: the influence of “donation by strangers” on the motivation and willingness of donor-patient couples, the issue of anonymity, the loss of the possibility of “medical excuses” for unwilling donors, the view that crossover is a first step to commercial organ donation, and the interference with existing organ donation programs. Earlier efforts suggest that none of these issues, separately or combined, seem to impede the efficient organisation of a crossover program or raise worrying ethical issues12 . Conclusions Simulations suggest that the most cost-effective modality for transplanting incompatible donor-recipient pairs is a national KPD program utilising an optimised matching algorithm35 . Almost all patients who would benefit from list paired donation are predicted to be better served by a national KPD program. With this evidence, and reports of excellent clinical outcomes from KPD, planning for a national KPD program should be a priority for the trans- plantation community36 . KPD programs can be successful, but relatively high numbers of candidates are needed, and thus cooperation between centres and trust among them is essential27 . In conclusion, the national KPD Portuguese program soon to be realised, may prevent the current loss of a significant number of suitable living donors, and thereby have a significant impact on the acute shortage of organs for transplantation in addition to the existing Portuguese live donor kidney transplant and deceased donor trans- plant programs. The described algorithm will help to en- sure an allocation program as equitable as possible based on medical criteria without compromising the number of potential transplants.
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