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BACKGROUND: The effect of HLA match on renal graft survival has become controversial as has the policy of
mandatory sharing of kidneys.
METHOD: We performed a retrospective analysis of HLA matched (M) and mismatched (MM) kidney transplants in
our center. Tacrolimus, mycophenolic acid, and steroids were used as maintenance therapy and basiliximab induction was added for high-risk patients.
RESULT: A total of 229 kidney transplants were included with median follow-up of 5.1 years. The 5-year deathcensored graft survival by Kaplan-Meier method was significantly higher in the M group than in the MM group for
deceased-donor kidney transplants (log-rank, p .018). This graft survival advantage was detected in patients with
a peak panel reactive antibody (PRA) greater than 20% (p .023), but not in those with a PRA level of less than 20%
(p .32). The graft survival was not statistically different for live donor kidney transplants (p .077). A mismatched
kidney was an independent risk for graft loss (hazard ratio: 2.27, 95% confidence interval: 1.0095.09, p .047)
and acute rejection was a significant cause of graft loss in mismatched deceased-donor transplants (p .035).
CONCLUSION: Acute rejection remains a significant cause of graft loss in HLA-6-antigen mismatched deceaseddonor kidney transplants. Our data support mandatory sharing of HLA-matched kidneys in sensitized patients with
a PRA level greater than 20%.
DOI: 10.1002/dat.20439
MM
Immunosuppressive therapy
Our standard triple immunosuppression regimen consisted of steroids, TAC,
and MFA. High risk patients defined as
prior transplant recipients, HLA-6-antigen
mismatch, and those with PRA levels greater than 20% received basiliximab induction
therapy. Intravenous methylprednisolone
was administrated prior to reperfusion and
tapered to maintenance oral prednisone.
TAC doses were adjusted to keep the 12hour trough levels between 10 to 12 ng/mL
for the first 3 months, 7 to 10 ng/mL for the
remainder of the first year, and 4 to 7 ng/
mL thereafter. Each patient received either
mycophenolate mofetil (MMF) at 1 gram
or enteric coated sodium mycophenolate
(Myfortic) at 720 mg twice daily.
(n 73)
(n 98)
p-value
48.33 14.96
45.25 15.17
.23
Female
33 (45.2%)
36 (36.7%)
.26
Male
40 (54.8%)
62 (63.3%)
African American
24 (32.9%)
72 (73.5%)
White
49 (67.1%)
23 (23.5%)
Others
0 (0%)
1 (3%)
26.9 6.04
27.36 6.76
.64
37.90 41.70
21.83 33.8
.01
Rejection
14 (19.2%)
11 (11.2%)
.14
CIT (hours)
18.91 6.56
17.45 6.96
.17
WIT (minutes)
28.92 6.1
29.86 8.52
.41
Deceased-donor
Kidneys
Age (years)
Sex
Race
BMI
Peak PRA (%)
Previous Transplants
<.0001
(n 26)
(n 32)
p-value
36.81 12.45
39.88 15.99
.53
Female
11 (42.3%)
13 (40.6%)
.92
Male
15 (57.7%)
19 (59.4%)
Live Kidneys
Age (years)
Sex
Race
African American
4 (15.4%)
13 (40.6%)
White
20 (74.1%)
17 (54.8%)
Others
2 (7.4%)
2 (6.5%)
BMI
27.66 6.81
27.18 7.64
.82
17.23 30.33
9.75 21.17
.29
5 (19.2%)
0 (0%)
.01
CIT (hours)
2.75 6.38
1.61 3.72
.43
WIT (minutes)
28.05 7.07
27.23 7.47
.67
Previous Transplants
.23
Statistical methods
Statistical analyses were performed using
SAS version 9.1.3 software (Cary, North
Carolina). A 2 or Fisher exact test was used
for count data and a t-test for continuous
MM
p-value
eGFR at 1 year
56.12 18.75
60.53 21.71
.18
eGFR at 3 year
58.89 21.1
55.88 24.43
.53
eGFR at 5 year
60.93 22.16
60.47 28.23
.94
10 (55.5%)
9 (28.1%)
.1
5 (27.7%)
7 (21.8%)
.9
0 (0%)
9 (28.1%)
.035
3 (16.6%)
7 (21.8%)
.70
eGFR at 1 year
57.31 15.83
61.2 26.75
.53
eGFR at 3 year
56.43 16.74
58.21 20.33
.77
eGFR at 5 year
54.62 20.51
58.45 25.51
.68
DWFG
2 (33.3%)
2 (22.2%)
.53
CAN
2 (33.3%)
3 (33.3%)
.62
Others
Live Kidneys
Graft Function
Acute Rejections
Others
0 (0%)
3 (33.3%)
.22
2 (33.3%)
1 (11.1%)
.25
measures. Product-limit estimates of survival curves were generated by KaplanMeier method and the survival difference
was analyzed by log-rank test. A multivariable Cox proportional hazard regression
analysis with a stepwise variable selection
was performed to examine the risk factors
for the graft loss. A p-value < .05 was considered statistically significant.
Results
A total of 229 consecutive kidney transplants that met the study criteria were identified during the 11-year period. Median
follow-up was 5.1 years (range, 12.1
132 months) as of December 2008 and
all were transplanted more than 1 year
before this study. Table I summarizes the
transplant recipient demographic characteristics of the 2 groups. There was no
difference in age, sex, body mass index
(BMI), warm ischemia time (WIT), or cold
TABLE II. Graft function and causes of graft loss between HLAmatched (M) and HLA-mismatched (MM) kidney transplants (mean
SD).
Discussion
FIGURE 1. The cumulative incidences of acute rejection between HLA-matched (M) and HLAmismatched (MM) kidney transplants according to donor origins. (A) Deceased donors; (B) living
donors.
FIGURE 2. Kaplan-Meier estimated death-censored graft survival between HLA-matched (M) and
HLA-mismatched (MM) deceased-donor kidney transplants.
4 Dialysis & Transplantation May 2010
FIGURE 4. Kaplan-Meier estimated death-censored graft survival between HLA-matched (M) and
HLA-mismatched (MM) living donor kidney transplants.
FIGURE 3. Kaplan-Meier estimated death-censored graft survival between HLA-matched (M) and
HLA-mismatched (MM) deceased-donor kidney transplants according to the panel reactive antibodies (PRA). (A) PRA <20%; (B) PRA >20%.
This study provides the first singlecenter data examining the effect of HLA
match on long-term graft survival. Among
the strengths of this study is the fact that
our patients were treated with 1 modern
immunosuppressive regimen, the previous
studies were based on either pooled multicenter data or UNOS data, and different
immunosuppressive protocols were used
in different transplant centers. Our study
is limited by its retrospective nature and
relatively small sample size in a single
center that prevents the study of the impact
of various HLA mismatching (1 to 5 HLAantigen mismatch).
Our data indicate that mandatory sharing
of HLA-matched kidneys remains beneficial
for sensitized patients with PRA levels greater than 20%. It not only increases the access
of kidney transplantation, but also provides
superior long-term graft survival in sensitized patients. The impact of HLA match has
become less consequential in low sensitized
patients as well as living-donor kidney transplants. Acute rejection remains a significant
cause of graft loss in HLA-6-antigen mismatched deceased-donor kidney transplants
who were treated by basiliximab induction
and tacrolimus, mycophenolic acid, and steroids as maintenance. More potent induction therapy may be needed to reduce the
incidence of rejection and to improve graft
survival in those high risk patients.
Acknowledgments
We thank the members of the Tulane
Abdominal Transplant Institute for maintaining the transplant data base. D&T
References
renal disease: a National Kidney Foundation/Kidney Disease Outcomes Quality Initiative (NKF/
KDOQITM) conference. Clin J Am Soc Nephrol.
2008;3(2):471-480.
6. Gaston RS, Danovitch GM, Adams PL, et al.
The report of a national conference on the wait
list for kidney transplantation. Am J Transplant.
2003;3(7):775-785.
7. Takemoto S, Terasaki PI, Gjertson DW, Cho YW,
Cecka JM. Survival of nationally shared HLAmatched kidney transplants from cadaveric
donors. N Engl J Med. 1992;327(12):834-839.
8. Takemoto SK, Terasaki PI, Gjertson DW, Cecka JM.
Twelve years experience with national sharing of
HLA-matched cadaveric kidneys for transplantation. N Engl J Med. 2000;343(15):1078-1084.
9. Stegall MD, Dean PG, McBride MA, Wynn JJ. Survival of mandatorily shared cadaveric kidneys and
their paybacks in the zero mismatch era. Transplantation. 2002;74(5):670-675.
10. Norman DJ. The kidney transplant wait-list: allocation of patients to a limited supply of organs. Semin
Dial. 2005;18(6):456-459.
11. U.S. Organ Procurement and Transplantation
Network and the Scientific Registry of Transplant
Recipients. 2008 OPTN/SRTR Annual Report:
Transplant Data 1998-2007. www.ustransplant.
org/annual_reports/curretn/data_tables_section5.html. Accessed October 15, 2009.
12. Su X, Zenios SA, Chakkera H, Milford EL, Chertow GM. Diminishing significance of HLA matching in kidney transplantation. Am J Transplant.
2004;4(9):150-158.
13. OPTN/UNOS Transplantation Committee. Report
to Board of Directors, June 2008. Available at:
http://unos.org/NewsDetail. Accessed October
15, 2009.
14. Opelz G, Dohler B. Effect of human leukocyte antigen compatibility on kidney graft survival: comparative analysis of two decades. Transplantation.
2007;84(2):137-143.
15. Lee CM, Carter JT, Alfrey EJ, Ascher NL, Roberts
JP, Freise CE. Prolonged cold ischemia time obviates the benefits of 0 HLA mismatches in renal
transplantation. Arch Surg. 2000;135(9):10161019.
16. Ceckaa JM, Reed EF. Histocompatibility testing,
crossmatch, and allocation of kidney transplants.
In: Danovitch G. Handbook of Kidney Transplantation, 4th ed. New York: Lippincott, Williams &
Wilkins; 2005:43-71.
17. Terasaki PI, Cecka JM, Gjertson DW, Takemoto
S. High survival rates of kidney transplants from
spousal and living unrelated donors. N Engl J Med.
1995;333(6):333-336.
18. Gjertson DW, Cecka JM. Living unrelated donor kidney transplantation. Kidney Int. 2000;58(2):491499.
23. Prommool S, Jhangri GS, Cockfield SM, Halloran PF. Time dependency of factors affecting renal allograft survival. J Am Soc Nephrol.
2000;11(3):565-573.
24. Hardinger KL, Brennan DC, Schnitzler MA. Rabbit
antithymocyte globulin is more beneficial in standard kidney than in extended donor recipients.
Transplantation. 2009;87(9):1372-1376.
25. Willoughby LM, Schnitzler MA, Brennan DC,
et al. Early outcomes of thymoglobulin and basiliximab induction in kidney transplantation: application of statistical approaches to reduce bias
in observational comparisons. Transplantation.
2009;87(10):1520-1529.
26. Taber DJ, Weimert NA, Henderson F, et al. Long-term
efficacy of induction therapy with anti-interleukin-2
receptor antibodies or thymoglobulin compared
with no induction therapy in renal transplantation.
Transplantation Proc. 2008;40(10):3401-3407.