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ORIGINAL ARTICLE
Year : 2022  |  Volume : 16  |  Issue : 1  |  Page : 56-60

Clinical outcome of ABO-Incompatible kidney transplant with low baseline anti-A/B antibody titer without the use of plasma exchange - A retrospective study


1 Department of Nephrology, Aditya Birla Memorial Hospital, Pune, Maharashtra, India
2 Department of Urology, Aditya Birla Memorial Hospital, Pune, Maharashtra, India
3 Department of Transfusion Medicine, Aditya Birla Memorial Hospital, Pune, Maharashtra, India

Date of Submission13-Jun-2021
Date of Acceptance05-Nov-2021
Date of Web Publication31-Mar-2022

Correspondence Address:
Dr. Tarun Kumar Jeloka
Department of Nephrology, Aditya Birla Memorial Hospital, Pune - 411 033, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_60_21

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  Abstract 


Background: The outcome of ABO-incompatible (ABOi) transplant (Tx) may be compromised because of the need for added immunosuppression. Many centers still use plasma exchange (PEX) even when anti-A/B titers are low. We compared the outcome of ABOi kidney Tx with low baseline anti-A/B titers without PEX to those with high titers managed with PEX and to ABO-compatible (ABOc) Tx. Materials and Methods: In this retrospective study, all adult kidney Tx done at our institute were eligible. Patients <18 years of age, deceased donor transplant recipients, and those with hepatitis B, C or HIV infections at the time of transplant were excluded from this analysis. Outcomes including biopsy-proven AR, estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease equation), infections, and patient and graft survival were determined in ABOi kidney Tx with low baseline anti-A/B antibody titers managed without PEX (Group A). These outcomes were compared to a contemporary cohort of those with high titers and use of PEX (Group B) and ABOc Tx (Group C). Continuous variables were compared by Student's t-test and categorical variables with Chi-square test. Patient and graft survival was calculated by Kaplan–Meier curve and compared between the groups by log-rank test. Results: Baseline characteristics reveal no difference in recipients and donor factors such as age, gender, and HLA match. Initial immunoglobulin G anti-A/B titers were higher in Group B as compared to Group A (P = 0.04), but final titers pretransplant were similar (P = 0.6). Biopsy-proven rejections were not different between Groups A and B or Groups A and C. Serum creatinine and eGFR at 1 month and at last follow-up were also similar in all the groups. Infections were seen in 22.2% of the patients in Group A, 44.4% in Group B, and 27.7% in Group C. Patient survival and death-censored graft survival were similar in all three groups. Conclusion: This retrospective study shows that patients with low baseline anti-ABO antibodies managed without PEX are safe and have similar outcomes such as patient and graft survival, rejections, infections, and renal function.

Keywords: ABOi transplant, ABO-incompatible transplant, anti-A/B titers, biopsy-proven rejection, end-stage renal disease, graft survival, plasma exchange, transplant complications, transplant survival


How to cite this article:
Jeloka TK, Dharaskar A, Singh R. Clinical outcome of ABO-Incompatible kidney transplant with low baseline anti-A/B antibody titer without the use of plasma exchange - A retrospective study. Indian J Transplant 2022;16:56-60

How to cite this URL:
Jeloka TK, Dharaskar A, Singh R. Clinical outcome of ABO-Incompatible kidney transplant with low baseline anti-A/B antibody titer without the use of plasma exchange - A retrospective study. Indian J Transplant [serial online] 2022 [cited 2022 May 25];16:56-60. Available from: https://www.ijtonline.in/text.asp?2022/16/1/56/342439




  Introduction Top


Kidney transplant is the desired treatment of end-stage renal disease (ESRD). Availability of suitable donors is an important limiting factor in kidney transplant. ABO-incompatible (ABOi) donor transplant is one such way to increase transplants in desiring patients.[1] Literature has shown comparable results with compatible transplants.[2] ABOi transplant requires pretransplant desensitization with rituximab for inhibiting antibody formation, and combination of plasma exchange (PEX), intravenous gamma globulin (IVIg), and/or adsorption cartridges for removal of preformed antibodies, depending on its titers.[3],[4] Those with low baseline titers may do away with removal and may need only rituximab.[5] Many centers still practice PEX before transplant, even when the titers are low, for the fear of rejection. There are limited studies available in the literature and none from India. We compared the outcome in cohort of ABOi kidney transplants with low baseline anti-A/B antibody titers managed without PEX to those with high titers managed with PEX and to compatible transplants during contemporary time zone.


  Materials and Methods Top


This was a retrospective, noninterventional study of ABOi kidney transplants done at Aditya Birla Memorial Hospital, Pune, between April 2014 and March 2020. Our ABOi transplant protocol included the use of rituximab and PEX for desensitization if the titers were <512. Those with higher than 512 titers received rituximab and adsorption cartridges for desensitization. Our acceptable pretransplant titer was 1:16. Since 2018, those with lower titers were managed with rituximab alone without any session of PEX. These were the cases (Group A). The outcome of this group was compared to ABOi transplants with higher baseline titers managed with PEX (Group B) and to ABO-compatible (ABOc) transplants. The selection of comparison groups was from contemporary time zone, closest to Group A in the ratio of 1:1:2, to avoid selection bias. All patients were managed with interleukin-2 antibody or antithymocyte globulin as induction and tacrolimus, mycophenolic acid sodium, and steroid as maintenance.

The primary objective was to compare the incidence of biopsy-proven acute rejection (AR) in Group A to those in Groups B and C. The secondary objectives were to compare estimated glomerular filtration rate (eGFR) at 1 month and last follow-up, infectious complications, and patient and graft survival between the groups.

  • Inclusion criteria – All adult kidney transplants done at our institute were eligible
  • Exclusion criteria – All kidney transplants below the age of 18 years, deceased donor transplants, and those with hepatitis B-, hepatitis C-, or HIV-positive status.


Statistical analysis

All continuous variables were determined as means and standard deviation, and all categorical variables were determined by percentage. Continuous variables were compared by Student's t-test and categorical variables with Chi-square test. Patient and graft survival was calculated by Kaplan–Meier curve and compared between the groups by log-rank test. Infections and rejections were calculated as percentage but statistically not compared as the rates were too low for comparison. P < 0.05 was regarded as significant. All data were analyzed using the Statistical Package for the Social Sciences (SPSS version 24, IBM Corporation, USA) for MS Windows.

Patient consent

The patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names and initials would not be published, and all standard protocols will be followed to conceal their identity.

Ethics statement

Ethics Committee approval was obtained for the study. A waiver was obtained from the Ethics Committee for waiving off of the consent, as this study was merely a review of data without intervention and without reveal of any patients' identity. Study was performed in accordance with the declaration of Helsinki.


  Results Top


A total of 198 transplants were done between April 2014 and March 2020. Out of these, 51 (25.7%) were ABOi. Out of these 51 ABOi transplants, 10 had baseline titers <1:16 and underwent transplant with rituximab and without PEX. One patient was excluded being HIV positive. Hence, a total of 9 patients were considered as cases (Group A). Of the remaining 41 ABOi patients with higher titers, 6 patients were excluded, 2 being pediatric and 4 being hepatitis B or C positive. Nine of these 35 ABOi transplants, transplanted closest to Group A, were selected for comparison. Of the 147 ABOc transplants, 4 were pediatric, 7 had hepatitis-positive status, and 35 were deceased donor, and hence excluded. Of the remaining 101 ABOc transplants, 18 patients were selected closest to each patient in Group A for comparison.

Baseline characteristics reveal no difference in age, gender, and HLA match [Table 1] in recipients. Initial immunoglobulin G anti-A/B titers were higher in Group B as compared to Group A (P = 0.04), but final titers pretransplant were similar (P = 0.6). Initial IgM titers were higher in Group B (P = 0.03), but final titers were lower as compared to Group A (P = 0.02). Donor factors such as age, gender, and relationship to recipient were all similar in all the groups. The mean follow-up was higher in Group B as compared to Group A (35 months vs. 15 months, P = 0.01), as it was not randomized but closest cohort. The blood groups of donors and recipients in the groups are shown in [Table 2] for comparison.
Table 1: Baseline characteristics of patients

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Table 2: Blood group of donors and recipients on ABOi and ABOc transplants

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Biopsy-proven rejections were not different between Groups A and B or Groups A and C. Group A had one acute antibody-mediated rejection (11.1%), Group B had three acute T-cell-mediated rejections (33.3%) with one patient having combined T-cell and antibody-mediated rejection (11.1%), and Group C had three acute T-cell-mediated rejections (16.6%) over the period of follow-up [Table 3]. Serum creatinine and eGFR (Modification of Diet in Renal Disease) at 1 month and at last follow-up were also similar in all the groups. Serum creatinine and eGFR at 1 month posttransplant were 1.3 ± 0.5 and 72.2 ± 23.3 in Group A, 1 ± 0.4 and 92.6 ± 33.5 in Group B, and 1.3 ± 0.4 and 70.2 ± 22.4 in Group C, respectively. Serum creatinine and eGFR at last follow-up posttransplant were 1.7 ± 0.9 and 59 ± 21.3 in Group A, 1.5 ± 0.7 and 57.7 ± 29.5 in Group B, and 1.3 ± 0.5 and 62.1 ± 30.5 in Group C, respectively.
Table 3: Various outcomes in ABO-incompatible and ABO-compatible transplants

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Infections were seen in 22.2% of the patients in Group A, 44.4% in Group B, and 27.7% in Group C [Table 3]. In Group A, one patient had fungal sepsis and another had gastrointestinal infection. In Group B, one patient had chickenpox, one had herpes zoster, and two had urinary tract infections. In Group C, one patient had graft pyelonephritis, one had Cryptococcus infection, one had tuberculosis, and two had urinary tract infections. Among other significant complications, new-onset diabetes after transplant (NODAT) was seen in three patients in Group A and three in Group C. Group B did not have any incidence of NODAT. Delayed graft function (DGF) was seen in one patient in Group A, two in Group B, and two in Group C.

Patient survival [Figure 1] and graft survival [Figure 2] were similar in all three groups [Table 2]. One patient died in each group, with actual survival being 88.9%, 88.9%, and 94.4% in Groups A, B, and C, respectively (log-rank Mantel–Cox 0.61). Death-censored graft failure did not happen in Group A but occurred in one patient in Group B and two in Group C. Actual graft survival was 100%, 88.9%, and 88.9% in Groups A, B, and C, respectively (log-rank Mantel–Cox 0.83).
Figure 1: Kaplan–Meier survival curves for patient survival in ABO-incompatible transplants with low titers, ABO-incompatible transplants with plasma exchange, and ABO-compatible transplants

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Figure 2: Kaplan–Meier survival curves for graft survival in ABO-incompatible transplants with low titers, ABO-incompatible transplants with plasma exchange, and ABO-compatible transplants

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  Discussion Top


Transplant is the definitive treatment for end-stage renal disease. However, there are limitations for recipients with blood group O without matched living donor, as they are less likely to get a “paired donation” transplant and their waiting time on the list is also longer.[6] Apart from live and deceased donor blood group-matched transplants, ABO mismatch transplant is another means to curb the shortage of donors and waiting time on dialysis. There are centers which are still not convinced in ABO mismatch transplants for reasons of outcome and higher cost.[7],[8] Irrespective of one's reasoning, ABOi kidney transplant offers an opportunity to a recipient for a transplant rather than waiting on dialysis for a deceased donor.[9] We have been performing ABOi transplants with desensitization since 2014 but of late realized that not all ABOi recipients require antibody removal.[10] This category of patients may not have increased cost as well. However, many centers opt to do at least one PEX before transplant even when the titers are lower than their cutoff. There is no report of outcome of ABOi transplants without PEX from India. Hence, we analyzed our data on outcomes of patients with low initial anti-A/B titers who did not undergo PEX.

The concern of success and safety of ABOi transplant has been studied and further evaluated by meta-analysis. However, there are limited data for patients with low anti-A/B titer ABOi transplants without antibody removal. Our data showed that estimated GFR and serum creatinine at 1 month posttransplant and over a median follow-up period of 15 months were similar in all the three groups, proving success in low titer group. Literature shows mixed results of rejections in ABOi transplants. de Weerd and Betjes[11] reported that biopsy-proven ARs were more common in ABOi transplants as compared to ABOc transplants (relative risk [RR], 1.39; 95% confidence interval [CI], 1.19–1.61; P = 0.001), and the difference was more pronounced with antibody-mediated rejections (RR, 3.86; 95% CI, 2.05–7.29; P = 0.001). Scurt et al. noticed no significant difference in overall, borderline, or T-cell-mediated rejections.[8] However, the proportion of patients with ABMR was higher in ABOi transplants.[8] In our study, overall biopsy-proven ARs were similar in all three groups. Overall, infections are reported to be higher in ABOi transplants.[8],[11] This is believed to be due to increase in degree of immunosuppression required for desensitization of ABOi transplant. The most common reported causes of death in ABOi transplants were infection related (49% vs. 13% in ABOc). Scurt et al.[8] mentioned in their meta-analysis that patient mortality was higher in the first 5 years after ABOi transplant and possibly because of over immunosuppression from desensitization resulting in life-threatening infections. Reduction in immunosuppression may alleviate this risk and hence improve the outcome of ABOi transplants. Although infection rates were higher in patients with higher titers managed with PEX, we did not find any statistical difference. We hypothesize that avoiding PEX in patients with lower initial anti-A/B titer may reduce the risk of infections.

Orandi et al.[12] in a multicenter study showed the survival benefit in ABOi transplant as compared to getting a deceased donor transplant or staying on dialysis. The survival benefit was at 1 year (95.0%, vs. 94.0% for the waiting list or transplant control group and 89.6% for the waiting list-only control group), 3 years (91.7% vs. 83.6% and 72.7%, respectively), 5 years (86.0% vs. 74.4% and 59.2%), and 8 years (76.5% vs. 62.9% and 43.9%). de Weerd and Betjes[11] noted in their meta-analysis that 1-year patient survival was lower in ABOi as compared to ABOc kidney transplants (98% versus 99%, P = 0.03). In our study, we found similar patient survival between all three groups.

Death-censored graft survival was similar between ABOi and ABOc kidney transplants in the largest registry study i.e. the Collaborative Transplant Study by Opelz et al.[2] and also in the study by Morath et al.[13] None of the 26 studies included in the meta-analysis by de Weerd and Betjes[11] showed difference in graft survival individually, but when taken together as part of meta-analysis, they found that 1-year graft survival in ABOi patients was lower (96% versus 98% for controls, P = 0.002) and remained lower at 3 years (92% versus 94%, P = 0.04). Similar results were shown by Scurt et al. in their meta-analysis.[8] The United Network for Organ Sharing data reveal inferior graft survival within the 1st year, similar to the results of the meta-analysis, but grafts surviving thereafter had comparable outcomes.[14] de Weerd and Betjes also showed that the overall uncensored graft loss at 1 year posttransplant in ABOi and ABOc transplant was 4.2% and 2.5%, respectively, which clinically may be a small difference when compared to staying on dialysis.[11]

Looking at evidences to make a conclusive decision on ABOi transplant is still limited. However, an interesting point of debate was made by Adnan Sharif in an editorial published recently in the American Journal of Kidney Diseases[15] that meaningful comparison can be made with patients waiting on dialysis. Massie et al. showed that proceeding with ABOi transplant poses an increased mortality risk within 30 days posttransplant as compared to staying on dialysis.[9] However, beyond 180 days, the mortality risk continued to be lower in ABOi transplant than on waiting list. Hence, Massie et al.'s study was in favor of ABOi transplant rather than waiting on dialysis. However, a similar study done in the UK by Manook et al. did not show any survival advantage of ABOi transplant as compared to waiting on dialysis.[16]

Limitations

The limitations of this study include being a single-center study and small number of patients with low titers. Overall, this retrospective study shows that patients with low baseline anti-ABO antibodies can be successfully managed without antibody removal procedures with equivalent success and comparable complications including ARs and survival, thereby offering an opportunity of ABO mismatch transplant rather than waiting on dialysis.


  Conclusion Top


This retrospective study shows that patients with low baseline anti ABO antibodies can be successfully managed without antibody removal procedures with equivalent success and comparable complications including ARs and survival, thereby offering an opportunity of ABO mismatch transplant rather than waiting on dialysis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Takahashi K, Saito K, Takahara S, Okuyama A, Tanabe K, Toma H, et al. Excellent long-term outcome of ABO-incompatible living donor kidney transplantation in Japan. Am J Transplant 2004;4:1089-96.  Back to cited text no. 1
    
2.
Opelz G, Morath C, Süsal C, Tran TH, Zeier M, Döhler B. Three-year outcomes following 1420 ABO-incompatible living-donor kidney transplants performed after ABO antibody reduction: Results from 101 centers. Transplantation 2015;99:400-4.  Back to cited text no. 2
    
3.
Montgomery RA, Locke JE, King KE, Segev DL, Warren DS, Kraus ES, et al. ABO incompatible renal transplantation: A paradigm ready for broad implementation. Transplantation 2009;87:1246-55.  Back to cited text no. 3
    
4.
Barnett AN, Manook M, Nagendran M, Kenchayikoppad S, Vaughan R, Dorling A, et al. Tailored desensitization strategies in ABO blood group antibody incompatible renal transplantation. Transpl Int 2014;27:187-96.  Back to cited text no. 4
    
5.
Masterson R, Hughes P, Walker RG, Hogan C, Haeusler M, Robertson AR, et al. ABO incompatible renal transplantation without antibody removal using conventional immunosuppression alone. Am J Transplant 2014;14:2807-13.  Back to cited text no. 5
    
6.
Glander P, Budde K, Schmidt D, Fuller TF, Giessing M, Neumayer HH, et al. The 'blood group O problem' in kidney transplantation – Time to change? Nephrol Dial Transplant 2010;25:1998-2004.  Back to cited text no. 6
    
7.
Langhorst C, Ganner A, Schneider J, Prager EP, Walz G, Pisarski P, et al. Long-term follow-up of ABO-incompatible kidney transplantation in Freiburg, Germany: A single-center outcome report. Transplant Proc 2020;1345:30353-5.  Back to cited text no. 7
    
8.
Scurt FG, Ewert L, Mertens PR, Haller H, Schmidt BM, Chatzikyrkou C. Clinical outcomes after ABO-incompatible renal transplantation: A systematic review and meta-analysis. Lancet 2019;393:2059-72.  Back to cited text no. 8
    
9.
Massie AB, Orandi BJ, Waldram MM, Luo X, Nguyen AQ, Montgomery RA, et al. Impact of ABO-incompatible living donor kidney transplantation on patient survival. Am J Kidney Dis 2020;76:616-23.  Back to cited text no. 9
    
10.
Kawamura T, Hamasaki Y, Takahashi Y, Hashimoto J, Kubota M, Muramatu M, et al. ABO-incompatible pediatric kidney transplantation without antibody removal. Pediatr Nephrol 2020;35:95-102.  Back to cited text no. 10
    
11.
de Weerd AE, Betjes MG. ABO-incompatible kidney transplant outcomes: A meta-analysis. Clin J Am Soc Nephrol 2018;13:1234-43.  Back to cited text no. 11
    
12.
Orandi BJ, Luo X, Massie AB, Garonzik-Wang JM, Lonze BE, Ahmed R, et al. Survival benefit with kidney transplants from HLA-incompatible live donors. N Engl J Med 2016;374:940-50.  Back to cited text no. 12
    
13.
Morath C, Zeier M, Do¨hler B, Opelz G, Su¨sal C. ABO-incompatible kidney transplantation. Front Immunol 2017;8: 234.  Back to cited text no. 13
    
14.
Futagawa Y, Terasaki PI. ABO incompatible kidney transplantation – An analysis of UNOS Registry data. Clin Transplant 2006;20:122-6.  Back to cited text no. 14
    
15.
Sharif A. Who benefits from ABO-incompatible kidney transplantation in the contemporary era? Am J Kidney Dis 2020;76:607-9.  Back to cited text no. 15
    
16.
Manook M, Koeser L, Ahmed Z, Robb M, Johnson R, Shaw O, et al. Post-listing survival for highly sensitised patients on the UK kidney transplant waiting list: A matched cohort analysis. Lancet 2017;389:727-34.  Back to cited text no. 16
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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