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Received: 29 November 2017 Revised: 20 February 2018 Accepted: 25 February 2018 DOI: 10.1111/ajt.14719
ORIGINAL ARTICLE
Impact of the new kidney allocation system A2/A2B → B policy on access to transplantation among minority candidates Paulo N. Martins1 | Margaux N. Mustian2 | Paul A. MacLennan2 | Jorge A. Ortiz1 | Mohamed Akoad1 | Juan Carlos Caicedo1 | Gabriel J. Echeverri1 | Stephen H. Gray1,2 | Reynold I. Lopez-Soler1 | Ganesh Gunasekaran1 | Beau Kelly1 | Constance M. Mobley1 | Sylvester M. Black1 | Carlos Esquivel1 | Jayme E. Locke1,2 1 American Society of Transplant Surgeons Diversity Affairs Committee, Arlington, VA, USA 2
Department of Surgery, Division of Transplantation, University of Alabama at Birmingham, Birmingham, AL, USA Correspondence Jayme E. Locke Email:
[email protected] Funding information NIH- National Research Service Award, Grant/Award Number: Grant Award Number T32 DK007545.
Blood group B candidates, many of whom represent ethnic minorities, have historically had diminished access to deceased donor kidney transplantation (DDKT). The new national kidney allocation system (KAS) preferentially allocates blood group A2/ A2B deceased donor kidneys to B recipients to address this ethnic and blood group disparity. No study has yet examined the impact of KAS on A2 incompatible (A2i) DDKT for blood group B recipients overall or among minorities. A case-control study of adult blood group B DDKT recipients from 2013 to 2017 was performed, as reported to the Scientific Registry of Transplant Recipients. Cases were defined as recipients of A2/A2B kidneys, whereas controls were all remaining recipients of non-A 2/A2B kidneys. A2i DDKT trends were compared from the pre-K AS (1/1/2013- 12/3/2014) to the post-K AS period (12/4/2014-2/28/2017) using multivariable logistic regression. Post-K AS, there was a 4.9-fold increase in the likelihood of A2i DDKT, compared to the pre-K AS period (odds ratio [OR] 4.92, 95% confidence interval [CI] 3.67-6.60). However, compared to whites, there was no difference in the likelihood of A2i DDKT among minorities post-K AS. Although KAS resulted in increasing A2/A2B→B DDKT, the likelihood of A2i DDKT among minorities, relative to whites, was not improved. Further discussion regarding A2/A2B→B policy revisions aiming to improve DDKT access for minorities is warranted. KEYWORDS
disparities, ethics and public policy, ethnicity/race, health services and outcomes research, kidney transplantation/nephrology, organ procurement and allocation
1 | I NTRO D U C TI O N
(DDKT) compared with candidates of other blood types, leading to diminished access to transplantation for this patient popula-
Blood group B kidney transplant waitlist candidates have histor-
tion.1,2 Moreover, many of the blood group B patients belong to
ically had lower rates of deceased donor kidney transplantation
ethnic minority groups, exacerbating existing disparities in access to transplantation for nonwhites, with increased time on the kid-
Abbreviations: A2, A, non-A1; A2B, AB, non-A1B; A2i, A2 incompatible; AA, African American; ABOc, ABO compatible; cPRA, calculated panel reactive antibody; DDKT, deceased donor kidney transplantation; KAS, kidney allocation system; OPTN, Organ Procurement and Transplantation Network; SRTR, Scientific Registry of Transplant Recipients; UNOS, United Network for Organ Sharing. Paulo N. Martins and Margaux N. Mustian are co-first authors.
Am J Transplant. 2018;1–7.
ney transplant waiting list for minorities.3 In fact, as of 2013, among blood group B candidates on the kidney transplant waitlist, more than 70% represented ethnic minorities. 2 It is recognized that a subtype of blood group A, specifically A2, has reduced antigen expression, and as such, functionally behaves
amjtransplant.com © 2018 The American Society of Transplantation | 1 and the American Society of Transplant Surgeons
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MARTINS et al.
2
like blood group O (universal donor blood type).4-6 In fact, results
multirace), and Hispanic ethnicity. There was very little missing co-
of A2-incompatible kidney transplantation (A2i: blood group A2 or
variate information: one recipient was missing cPRA; 16 (0.2%) were
A2B donor → blood group B recipient) have demonstrated similar
missing diabetes diagnosis; and there was no missing information for
graft and patient outcomes as ABO compatible (ABOc) DDKT (blood
the remaining covariates. Given the low frequency of missing data,
group B or O donor → blood group B recipient) without the need for
we present a complete case analysis.
7,8
immune modulation.
Furthermore, one organ procurement orga-
nization found an increase of over 30% in the transplantation rate for blood group B candidates, following preferential allocation of A2 and A2B donor kidneys in their region.9
2.1 | Statistical analysis Chi-square tests and nonparametric tests were used to compare
However, despite the excellent allograft and patient outcomes
cases to controls for categorical and continuous variables, respec-
reported, A2i transplantation has been underutilized in the past,
tively. Multivariable logistic regression was used to estimate the
with less than 15% of A2 kidneys from deceased donors used for A2i
probability A2i DDKT by KAS era and by demographic, patient, and
DDKT recipients as of 2010.10 Not surprisingly, given the encour-
waitlist factors. Crude and adjusted odds ratios (ORs) and 95% confi-
aging early results following A2i transplantation and the potential
dence intervals (CIs) were calculated for the likelihood of A2i DDKT
to mitigate disparities in access to DDKT among predominately mi-
overall and stratified by KAS era. Fully adjusted models included
nority blood group B candidates, the new kidney allocation system
race, Hispanic ethnicity, gender, age, diabetes, OPTN region, wait-
(KAS, implemented December 2014) incorporated a provision for
list years, and cPRA. Significant multiplicative interactions between
the preferential allocation of A2 and A2B kidneys to blood group B
pre-and post KAS periods, waitlist duration and race, and dialysis
transplant candidates. To date, no study has assessed the impact of
duration and race were assessed using cross-product terms in ad-
KAS on A2i DDKT rates or assessed the impact of this aspect of the
justed models.
policy change on existing disparities in transplant rates among blood
To examine whether the likelihood of A2i DDKT differed by the
group B ethnic minorities. Herein, we present the first national study
centers’ proportion of minority groups (AA, Asian, and Hispanic eth-
to examine the likelihood of A2i DDKT, overall and by ethnicity, in
nicity) waitlisted, logistic regression stratified by KAS era was used
the post-K AS era.
to estimate the probability A2i DDKT among recipients based on the proportion of minorities waitlisted at centers. We calculated the
2 | M ATE R I A L A N D M E TH O DS
numbers of these candidates among all adult blood group B candidates ever listed at the center level between December 4, 2014 and February 28, 2017. From this, center quartile categories were de-
This study used data from the Scientific Registry of Transplant
fined for all type B recipients as the proportion of centers’ blood
Recipients (SRTR). The SRTR data system includes data on all donor,
type B candidates that were AA (0-20.8%, 20.9-4 0.4%, 40.5-58.5%,
wait- listed candidates, and transplant recipients in the United
and >58.5%), Asian (0-4.5%, 4.6-8.9%, 9.0-17.1%, and >17.1%),
States, submitted by the members of the Organ Procurement
and Hispanic ethnicity (0-2.0%, 2.1-7.0%, 7.1-16.1%, and >16.1%).
and Transplantation Network (OPTN). The Health Resources and
Recipient race, Hispanic ethnicity, and OPTN region were excluded
Services Administration (HRSA), US Department of Health and
from multivariable models.
Human Services provides oversight to the activities of the OPTN and
We conducted sensitivity analyses for the association of KAS era
SRTR contractors. This study received approval from the University
and patient factors, such as cPRA (categorical: ≥80% and continu-
of Alabama at Birmingham Institutional Review Board.
ous), waitlist time, dialysis time, minority proportions among centers
Using SRTR’s standard analytical files, a case-control study de-
wait list population, and the likelihood of A2i DDKT transplanta-
sign was carried out. Eligible subjects for inclusion in the study were
tion1; full models with the addition of dialysis time were created to
adult blood group B recipients of deceased donor kidneys trans-
examine the effect of minority proportions among centers’ wait-
planted between January 2013 and February 2017. Cases were
list population; and2 parsimonious regression models were created
defined as A2i DDKT recipients. Controls were defined as blood
using backward selection methods, which included only covariates
group B DDKT recipients of all other donor blood types, and were
significant at alpha 30); there was no significant multiplicative
and shows a comparison of A2i DDKT recipients and ABOc DDKT
interaction observed for cPRA and race and the likelihood of A2i
recipients, demonstrating no significant differences in the 2 groups
transplantation (P = .75). There was significant variation in likelihood
by recipient race (P = .75) and ethnicity (P = .08). However, recipi-
of A2i DDKT based on OPTN region (P = .01).
ents of A2/A2B kidneys were significantly more likely to be male
When evaluating centers’ implementation of A2i DDKT based
(P = .003), and older than 55 years (P = .04). Recipient dialysis du-
on their proportion of AA minority patients, we found that during
ration was significantly shorter among A2i recipients (P 55 years Waitlist years, median
2.3
2.4
0.97 (0.93-1.01)
Dialysis years, median
3.4
4.5
0.91 (0.89-0.94)
regions with high minority waitlist populations have increased odds of A2i DDKT in order to fully address the issue of minority access to kidney transplantation. Although center level population demographics suggest that there has been a decrease in disparity in access to A2i DDKT, there remains a large opportunity to improve the utiliThe implementation of KAS in 2014 was not the first attempt
285 (72.9)
3547 (58.1)
1-3 0
52 (13.3)
928 (15.2)
0.70 (0.51-0.95)
31+
54 (13.8)
1627 (26.7)
0.41 (0.31-0.56)
Diabetes (%)
163 (41.7)
2247 (36.8)
1.23 (1.00-1.51)
Delayed graft function
86 (22.0)
1657 (27.2)
0.76 (0.59-0.97)
REF
that the OPTN had made to address ethnic and blood group disparities in access to kidney transplantation. In 2002, a national variance of practice was established that would permit the utilization of A2 deceased donor kidneys for blood group B recipients with low anti-A immunoglobulin titer levels.8 However, following this policy change, the acceptance and transition of practice to reduce disparities was
KAS period Pre-K AS (01/01/13- 12/03/14)
53 (13.6)
Post-K AS (12/04/14- 02/28/17)
338 (86.5)
2658 (43.6)
found to lag behind protocol. Previous studies have observed a small
REF
acceptance of A2i DDKT for blood group O and B recipients following the national allocation variance in 2002,10 and the results of our study
3445 (56.5)
4.92 (3.67-6.60)
also illustrate that the acceptance and use of A2i DDKT among blood group B recipients following the implementation of KAS in 2014 still remains underutilized. Because one of the aims of the A2/A2B allocation variance in 2002, similar to the goal of KAS, was to increase
OPTN region 0 (-)
240 (3.9)
UNDa
access to transplantation for minority groups, Williams et al sought to analyze the efficacy of the allocation changes, finding that 61% of
2
61 (15.6)
868 (14.2)
1.16 (0.79-1.70)
3
51 (13.0)
841 (13.8)
REF
4
31 (7.9)
525 (8.6)
0.97 (0.62-1.54)
5
35 (9.0)
1013 (16.6)
0.57 (0.37-0.88)
6
42 (10.7)
194 (3.2)
3.57 (2.31-5.53)
7
16 (4.1)
465 (7.6)
0.57 (0.32-1.01)
8
36 (9.2)
390 (6.4)
1.52 (0.98-2.37)
9
52 (13.3)
435 (7.1)
1.97 (1.32-2.95)
10
19 (4.9)
432 (7.1)
0.73 (0.42-1.24)
11
48 (12.3)
700 (11.5)
1.13 (0.75-1.70)
the A2i DDKT blood group B recipients were nonwhite.8 In our study, however, we found no increase in the likelihood of A2i DDKT for AAs or Hispanics in the post-KAS period. This further demonstrates that although there have been some mild improvements in the utilization of A2i DDKT following KAS, the changes may not have been as great as what had previously been appreciated following the prior variance of practice in 2002 and perhaps further revisions to existing policy should be considered to ensure improved access to DDKT for ethnic and racial minorities. Similar to the results of our study, the OPTN/SRTR 2015 Annual Data Report demonstrated that the total number of A2i DDKT
Center proportion of AAs among blood group B WL 0.21-0.40
be beneficial to see this trend continue to improve to the point that
zation of A2i DDKT for minority groups.
cPRA
55 years
0.62 (0.36-1.09)
0.51 (0.29-0.91)
1.50 (1.20-1.88)
1.47 (1.16-1.86)
Wait list years, median
0.81 (0.70-0.93)
0.81 (0.71-0.94)
1.02 (0.97-1.06)
1.04 (1.00-1.09)
Diabetes
1.40 (0.81-2.42)
1.51 (0.86-2.66)
1.27 (1.01-1.60)
1.06 (0.84-1.36)
cPRA 0
1.0 (ref)
1.0 (ref)
1.0 (ref)
1.0 (ref)
1-3 0
0.85 (0.39-1.84)
1.00 (0.46-2.19)
0.65 (0.47-0.91)
0.66 (0.47-0.93)
31+
0.45 (0.20-1.00)
0.48 (0.21-1.12)
0.38 (0.28-0.53)
0.42 (0.30-0.58)
1
UNDb
UNDb
UNDb
UNDb
2
b
b
1.79 (1.16-2.76)
1.76 (1.13-2.70)
OPTN regiona
3
UND
UND
1.0 (REF)
1.0 (REF)
1.0 (REF)
1.0 (REF)
4
0.80 (0.34-1.89)
0.85 (0.34-2.12)
1.06 (0.61-1.82)
1.06 (0.61-1.85)
5
UNDb
UNDb
0.89 (0.55-1.45)
0.82 (0.49-1.35)
6
4.67 (2.29-9.55)
5.36 (2.34-12.31)
3.07 (1.75-5.37)
2.76 (1.54-4.94)
7
0.43 (0.14-1.32)
0.49 (0.16-1.52)
0.64 (0.33-1.25)
0.63 (0.32-1.23)
8
0.80 (0.32-1.97)
0.74 (0.29-1.87)
2.06 (1.23-3.46)
2.00 (1.18-3.40)
9
UNDb
UNDb
2.72 (1.73-4.28)
2.33 (1.47-3.71)
b
UNDb
1.15 (0.64-2.05)
1.06 (0.59-1.90)
UND
1.68 (1.07-2.65)
1.83 (1.15-2.90)
10
UND
11
UND
a
Adjusted ORs for OPTN region restricted to regions that had at least one A2i DDKT. UND, Undefined odds ratio could not be calculated, as there were no observed A2/A2B to B transplantations performed in that region. b
transplantation in the post-K AS era.11 In their analysis, they also
great enough to counteract the disparities that still exist. Minority
found that minority disparities in access to transplantation had
disparities in kidney transplantations have been found to occur on
shifted slightly following KAS, with AA recipients accounting for
many levels, with ethnic minorities receiving fewer kidney trans-
37.8% of all recipients post-K AS, compared with 31.1% prior to
plants, partly due to racial differences in clinical characteristics
the new allocation system.11 Other studies, when analyzing gen-
such as blood group status, but even after accounting for clinical
eral transplantation trends following KAS implementation, have
differences, an underutilization of kidney transplantation among mi-
also found a rise in the rate of kidney transplantation for AAs and
norities has been found.14,15 Compared to their white counterparts,
Hispanics following KAS,12,13 but a lower rate for DDKT among
end-stage renal disease disproportionately affects AAs and Asians,
blood group B candidates compared to other ABO groups has also
while both of these minority groups are less likely to undergo kidney
been appreciated.13 This may explain some of the differences in
transplantation, demonstrating the importance of continued efforts
our findings when looking specifically at A2i transplantation rates
to address and reduce disparities in access to transplantation for
among blood group B recipients.
ethnic minorities.3,15
Moreover, as we found in our study, the increase in minority
This study is not without limitations. This was a retrospective
representation in the A2i DDKT population has not been as great
analysis from a large database, and as such we were restricted by
as expected following the implementation of KAS, and likewise
the available information and may not have accounted for all poten-
the increase in minority access to transplantation does not appear
tial confounding. Moreover, given the limited granularity of the data
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MARTINS et al.
6
Pre-K AS (01/01/2013-12/03/2014)
Post-K AS (12/04/2014-02/28/2017)
OR (95% CI)
OR (95% CI)
aOR (95% CI)
aOR (95% CI)
Center proportion AA on blood group B WL
