Renal Transplantation in High Immunological Risk Patients: A
Single-Center Experience
Nadir Alpaya,*, Ümit Özçelikb, Eryigit Erenc, and Bora Uslud
aDepartment of Nephrology, _Istanbul Aydın University Training and Research Hospital;bDepartment of General Surgery, Istanbul Aydın
University Training and Research Hospital;cDepartment of General Surgery, Istinye University Training and Research Hospital; and dDepartment of Nephrology, Istinye University Training and Research Hospital
ABSTRACT
Background. Renal transplantation (RT) in high-risk patients is increasingly performed due to an inadequate organ pool and increased rate of RT after a failed transplantation. Safety and prognosis of RT in such patients with high risk is an ongoing debate. Herein we aimed to present our single-center experience on RT of high-risk patients.
Methods. A total of 89 consecutive RT patients were included into this study in a 10-month period. Patients were divided into 3 groups: the low-risk group (n ¼ 47) with negative panel reactive antibody (PRA), medium-risk group (n ¼ 18) with positive PRA but mean fluorescence intensity (MFI) < 2000, and high-risk group (n ¼ 24) with positive PRA and MFI >2000 or donor specific antibody (DSA) positivity. Groups were compared in terms of demographic features, serum creatinine levels, acute rejection rates, delayed graft function (DGF), and patient or graft loss.
Results. Age of the recipients were similar between the groups. Desensitization (7% vs 11% vs 42%, respectively, in low-, medium-, and high-risk groups; P ¼ .001), plasmapheresis (6% vs 11% vs 46%, respectively, P < .001), and rituximab treatments (0% vs 0% vs 25%, respectively,P < .001) were significantly more frequently performed in high-risk patients. Serum creatinine levels at 1 month and 6 months after RT were similar between the groups (P ¼ .43 and P ¼ .71, respectively). Rates of acute rejection (6% vs 6% vs 16%, respectively, P ¼ .52) and DGF (9% vs 11% vs 29%, respectively, P ¼ .15) were similar between the groups. Frequencies of loss of patient or graft were also similar (0% vs 6% vs 4%,P ¼ .15).
Conclusion. RT may be successfully performed in high-risk patients without an increase in the risk of acute rejection, DGF, or patient/graft loss.
R
ENAL transplantation (RT) is known to be associated with improved survival and quality of life compared to patients on dialysis. However, highly sensitized RT candi-dates usually have long waiting times, causing increased morbidity and mortality in this patient population[1]. Recent advances to overcome this issue include desensitization protocols and paired donor exchange. RT in high-risk pa-tients is increasingly performed due to inadequate organ pool and increased rate of RT after a failed transplantation. Safety and prognosis of RT in such patients with high risk is an ongoing debate. Herein we aimed to present our single-center experience on RT of high-risk patients.MATERIALS AND METHODS
A total of 89 consecutive RT patients were included in this study during a 10-month period. All patients received induction treatment with anthymocyte globulin and standard immunosuppressive
*Address correspondence to Nadir Alpay, _Istanbul Aydın Uni-versity School of Medicine, _Istanbul Aydın University Training and Research Hospital, Department of Nephrology, Bes¸yol Mahallesi, Akasya Sokak no: 4, Küçükçekmece, 34295, Istanbul, Turkey. Tel: þ90 505 713 9779, Fax: þ90 212 979 5999. E-mail:
drnadiralpay@hotmail.com
0041-1345/19
https://doi.org/10.1016/j.transproceed.2019.04.075 230 Park Avenue, New York, NY 10169ª 2019 Published by Elsevier Inc.
treatment (tacrolimus, mycophenolic acid, prednisolone). Patients were divided into 3 groups: the low-risk group (n ¼ 47) with negative panel reactive antibody (PRA), medium-risk group (n¼ 18) with positive PRA but MFI <2000, and high-risk group (n ¼ 24) with positive PRA and MFI >2000 or donor specific antibody (DSA) positivity. Groups were compared in terms of de-mographic features, serum creatinine levels, acute rejection rates, delayed graft function (DGF), and patient or graft loss.
Patients whose primary kidney disease was focal segmental glo-merulosclerosis also received plasmapheresis. These patients were not at high risk, but they received plasmapheresis as a treatment modality of focal segmental glomerulosclerosis.
STATISTICAL ANALYSIS
Statistical analysis was performed with the Statistical Package for Social Sciences for Windows version 16.0 (SPSS Inc, Chi-cago, IL, USA). Results of the data with normal distribution were expressed as mean standard deviation. Data with non-normal distribution were presented as median (interquartile range: 25% to 75%). Two-tailedP value of < .05 was defined as statistically significant.
RESULTS
Baseline demographic, clinical, and treatment data of all pa-tients are presented inTable 1. Comparison of the groups in terms of these data is presented inTable 2. Accordingly, age of the recipients was similar between the groups. Desensitization (7% vs 11% vs 42%, respectively, in the low-, medium-, and high-risk groups;P ¼ .001), plasmapheresis (6% vs 11% vs 46%, respectively,P < .001), and rituximab treatments (0% vs 0% vs 25%, respectively,P < .001) were significantly more frequently performed in high-risk patients. Outcome data including acute rejection and DGF rates, serum creatinine levels, and graft and patient survival rates are presented in Table 2. Serum creatinine levels at 1 month and 6 months after RT were similar between the groups (P ¼ .43 and P ¼ .71, respectively). Rates of acute rejection (6% vs 6% vs 16%, respectively,P ¼ .52) and DGF (9% vs 11% vs 29%, respec-tively,P ¼ .15) were similar between the groups. Frequencies of loss of patient or graft were also similar (0% vs 6% vs 4%, P ¼ .15).
Cytomegalovirus developed in 2 patients and BK virus developed in 2 patients during the 8-month follow-up period. Two patients with a cytomegalovirus infection were in the high-risk group. These patients had an acute rejection and received additional antirejection treatment (steroid, antithymocyte globulin). One of the patients with a BK virus infection was in the high-risk group, and the other patient was in the medium-risk group.
DISCUSSION
In this paper, we tried to present the outcome data of RT performed on high-risk patients. Although desensitization treatments were significantly more frequently performed in this patient group, acute rejection and DGF rates and graft
and patient survivals were similar between the high- and low-risk groups.
Patients with a history of a failed RT, multiple pregnan-cies, blood transfusions, PRA positivity, and presence of DSA are regarded as having high risk. These patients have higher risk of acute rejection and early graft loss. Thus, such highly sensitized patients always have a limiting access to RT[2].
Most studies about the desensitization outcomes are small and nonrandomized with short follow-up times[3]. In a study by Montgomery et al, a clear survival benefit for desensitization was alternate day plasmapheresis and low dose intravenous immunoglobulin (IVIG) in living donor kidney transplantation compared to dialysis patients[4].
In a study by Vo et al[5], desensitization with Rituximab and high-dose IVIG-based regimen was evaluated. In this
Table 1. Baseline Demographic, Clinical, and Treatment Data of All Patients
Baselines Characters N¼ 89 patients Recipient mean age (years) 41.9 13.6
Donor mean age 47.4 13.1
Gender M 54 (60.7%) F 35 (39.3%) Recipient BMI 25.4 5.7 Donor BMI 27.8 5.2 Tx number First (1) 77 (86.5%) Second (2) 10 (11.2%) Third (3) 2 (2.2%)
Paired living exchange transplantation 9 (10%) Blood transfusion (þ) 40 (44.9%) (-) 49 (55.1%) Preemptive Tx (þ) 31 (34.8%) (-) 58 (65.2%) HLA mismatch 0 12 (13.5%) 1 1 (1.1%) 2 11 (12.4%) 3 31 (34.8%) 4 11 (12.4%) 5 11 (12.4%) 6 12 (13.5%) Desensitization (þ) 15 (16.9%) (-) 74 (83.1%) Plasmapheresis 16 (18%) Rituximab 6 (6.7%) IVIG 1 Acute Rejection (þ) 9 (10.1%) (-) 80 (89.9%)
Delayed graft function (DGF)
(þ) 15 (16.8%)
(-) 74 (83.1%)
study, patient survival and allograft survivals at 1 year were found to be 100% and 94%, respectively.
In a larger study with 76 patients who were transplanted after desensitization, 31 patients received living donor kidneys, and 45 patients received deceased donor kidneys[6]. Waiting time for transplant was reduced from 95 months to 4 months after desensitization. Patient and overall graft survivals at 2 years were reported to be 95% and 84%, respectively.
In the study by Yabu et al, RT experience on 5 highly sensitized patients, all with cumulative PRA 100%, who un-derwent desensitization in combination with kidney paired donation and successfully received kidney transplants, were presented. In this study, patients received desensitization therapy consisted of monthly high-dose IVIG, rituximab, IVIG, and plasmapheresis. Only 1 patient received bortezo-mib who did not respond to the mentioned desensitization protocol. All 5 patients were successfully transplanted: 3 with living donors through kidney paired donation and two with deceased donors. At follow-up, graft functions were stable, and no patient developed post-transplant DSA. In this paper, the authors concluded that early enrollment into paired donor exchange programs and desensitization protocols are important for successful and timely RT in these high-risk patients [7]. In another study by Shaffer et al [8], 3-year outcomes in 29 highly sensitized patients who were desensi-tized with high-dose IVIG and 1 dose of Rituximab after transplantation were presented. In this study, 3-year patient and graft survival were 95% and 90%, respectively.
Short-term graft survivals and acute antibody-mediated rejection rates were reported to be high in high-risk
patients [3,9,10]. However, in our cohort, acute rejection was observed in 4 patients (16%), which was not statistically different from the low-risk patients. Long-term follow-up results are important in this regard, and further studies about the long-term results of the desensitization programs should be performed.
CONCLUSION
RT may be successfully performed in high-risk patients without an increase in the risk of acute rejection, DGF, or patient/graft loss.
REFERENCES
[1] Keith DS, Vranic GM. Approach to the highly sensitized kidney transplant candidate. Clin J Am Soc Nephrol 2016;11: 684e93.
[2] Sanoff SL, Balogun RA, Lobo PL. The role of therapeutic apheresis in high immunologic risk renal transplantation: a review of current trends. Semin Dial 2012;25:193e200.
[3] Pham TA, Lee JI, Melcher ML. Kidney paired exchange and desensitization: Strategies to transplant the difficult to match kidney patients with living donors. Transplant Rev (Orlando) 2017;31: 29e34.
[4] Montgomery RA, LB, King KE, et al. Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med 2011;365:318.
[5] Vo AA, Lukovsky M, Toyoda M, et al. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med 2008;359:242e51.
[6] Vo AA, Peng A, Toyoda M, et al. Use of intravenous immunoglobulin and rituximab for desensitization of highly
HLA-Table 2. Comparison of the Groups
Low-Risk Group (n¼ 47) Medium-Risk Group (n¼ 18) High-Risk Group (n¼ 24) P
Recipient mean age 40.9 14.4 43.5 13.1 42.6 12.4 .759
Donor mean age 47.7 13.1 50.5 13.8 44.4 12.8 .303
BMI (kg/m2) 25.2 5.6 25.3 5.1 26 6.3 .919 Blood transfusion 20 9 11 .054 Pregnancy 7/13 (54%) 8/11 (73%) 8/11 (73%) .054 HLA mismatch 0 6 3 3 .700 1 7 2 2 2 6 1 4 3 13 8 10 4 7 1 3 5 0 0 1 6 8 4 1 Desensitization 3 (6.4%) 2 (11.1%) 10 (41.7%) .001 Plasmapheresis 3 (6.4%) 2 (11.1%) 11 (45.8%) <.001 Rituximab 0 0 6 (25%) <.001 IVIG 0 0 1 .254 Acute rejection 2 (6%) 1 (6%) 4 (16%) .520
Delayed graft function 5 (9%) 2 (11%) 8 (29%) .152
1. Month creatinine (mg/dL) 0.9 1.02 1.1 .43 6. Mount creatinine (mg/dL) 1.02 1.1 1.23 .71 Survival .152 1-Functional graft 47 17 23 2-Dialysis 0 0 1 3-Death 0 1 0
sensitized patients awaiting kidney transplantation. Transplantation 2010;89:1095e102.
[7] Yabu JM, Pando MJ, Busque S, Melcher ML. Desensitiza-tion combined with paired exchange leads to successful trans-plantation in highly sensitized kidney transplant recipients: strategyandreport of 5 cases. Transplant Proc 2013;45:82e7.
[8] Shaffer D, Feurer ID, Crowe D, Schaefer H. Early and sus-tained reduction in donor-specific antibodies in desensitized living
donor kidney transplant recipients: a 3-year prospective study. Transplant Direct 2016;2(2):e62.
[9] Montgomery RA, Zachary A. Transplanting patients with a positive donor-specific crossmatch: a single center’s perspective. Pediatr Transplant 2004;8:535e42.
[10] Schweitzer EJ, Wilson JS, Fernandez-Vina M, et al. A high panel-reactive antibody rescue protocol for crossmatch-positive live donor kidney transplants. Transplantation 2000;70:1531.
