|Year : 2020 | Volume
| Issue : 4 | Page : 346-348
A case report of ABO and human leukocyte antigen incompatible renal transplant – Being immunologically smart
Pranaw Kumar Jha1, Ajay Kher2, Vijay Kher1
1 Department of Nephrology and Renal Transplantation, Medanta Institute of Kidney and Urology, Gurugram, Haryana, India
2 Department of Nephrology, Max Super Speciality Hospital, Ghaziabad, Uttar Pradesh, India
|Date of Submission||08-Jul-2020|
|Date of Acceptance||04-Oct-2020|
|Date of Web Publication||30-Dec-2020|
Dr. Pranaw Kumar Jha
Department of Nephrology and Renal Transplantation, Medanta Institute of Kidney and Urology, Medanta – The Medicity, Sector-38, Gurugram - 122 001, Haryana
Source of Support: None, Conflict of Interest: None
Blood group and human leukocyte antigen (HLA) incompatibility are major immunological barriers in renal transplantation. Desensitization and subsequent transplantation improve the longevity and quality of life of these patients when compared to being on a waitlist. For best outcomes, a complete repertoire of immunological workup and an in-depth understanding of these tests are important for choosing the most suitable donor against whom the recipient is least sensitized. We present an interesting case of a sensitized patient who had the option of undergoing renal transplant with either a blood group incompatible mother or a compatible aunt as the prospective donor. Despite the blood group incompatibility, the mother was chosen as the donor in view of the lower strength of anti-HLA antibodies against her. The patient had a successful posttransplant outcome with good graft function at 1 year follow-up. Careful donor selection after detailed immunological workup is important while transplanting sensitized recipients. HLA incompatibility rather than blood group incompatibility should be the deciding factor in such cases.
Keywords: Blood group incompatibility, desensitization, human leukocyte antigen incompatible, kidney transplantation
|How to cite this article:|
Jha PK, Kher A, Kher V. A case report of ABO and human leukocyte antigen incompatible renal transplant – Being immunologically smart. Indian J Transplant 2020;14:346-8
|How to cite this URL:|
Jha PK, Kher A, Kher V. A case report of ABO and human leukocyte antigen incompatible renal transplant – Being immunologically smart. Indian J Transplant [serial online] 2020 [cited 2021 Jan 22];14:346-8. Available from: https://www.ijtonline.in/text.asp?2020/14/4/346/305434
| Introduction|| |
Renal transplantation is the best treatment for patients with end-stage renal disease (ESRD). Unfortunately, almost 54% of the willing donors can potentially get rejected due to immunological barriers of blood group incompatibility and human leukocyte antigen (HLA) sensitization. Although deceased donor transplants and paired kidney exchange (PKE) can be helpful in such cases, it is not always feasible. Such patients can be successfully transplanted after desensitizing them, but the donor selection should be done carefully, choosing the one against whom the recipient is minimally sensitized. The present case emphasizes this point.
| Case Report|| |
A 23-year-old female was on maintenance hemodialysis since April 2015. She had a history of severe postpartum hemorrhage leading to acute cortical necrosis. She had required multiple blood transfusions (8 units). Her other comorbidities included hypothyroidism for 2 years.
Long-term renal replacement therapy was discussed with the patient and her family and they opted for renal transplantation. Her blood group was O positive. The willing blood group compatible donors were father and maternal aunt. After the initial donor workup, complement-dependent cytotoxicity (CDC) and flow cytometry crossmatch were done. CDC and B cell flow cytometry crossmatch with father was positive and hence he was rejected. Next, the maternal aunt underwent a complete workup followed by immunological investigations. CDC crossmatch was negative, but the flow cytometry crossmatch came positive (both T and B cell). A flow cytometry panel reactive antibody was done which confirmed the highly sensitized status of the recipient (Class 1- 48% positive and Class 2- 83% positive). Single-antigen bead assay by Luminex showed multiple Class 1 (against A antigen) and Class 2 antibodies (against DRB and DQ antigens).
She was registered for deceased donor transplantation. There was no suitable pair with O group donor for PKE. The option of considering the mother (blood group B positive) as a donor for ABO-incompatible (ABOi) renal transplant and the risk involved in such transplants (chances of hyperacute rejection) was discussed but the patient and family were unwilling for the same.
The patient continued maintenance hemodialysis at her native place and subsequently developed hepatitis C infection (genotype 1a) in 2018. She was treated with sofosbuvir and ledipasvir for 3 months and went into remission. In view of deteriorating clinical condition and dialysis-related complications, the patient and family came back for transplantation. The mother was worked up as a donor. The patient's anti-B blood group antibody titer (immunoglobulin G) was 1024. After complete donor evaluation, CDC and flow crossmatch was done which showed negative CDC but weakly positive T-cell flow crossmatch and positive B-cell crossmatch. A repeat crossmatch with the aunt showed positive T and B flow crossmatch [Table 1]. HLA typing of the patient, mother, and aunt is also shown in [Table 1]. HLA typing showed 2/6 mismatch with the mother and 5/6 mismatch with the aunt. Repeat single-antigen bead test was also done [Table 2]a which showed class 1 and 2 antibodies against the aunt but only class 2 antibodies against the mother.
Considering the patient's higher sensitization status against the aunt, the mother was chosen as donor despite blood group incompatibility. The patient underwent desensitization as per the center protocol. After crossmatch test results the patient received IV rituximab 200 mg (day-25). One week after this oral tacrolimus was started at 0.05 mg/kg/day in two equal divided doses and MMF-S at 720 mg twice daily. Cascade plasmapheresis (CP) was started at this juncture (day-18). Five grams of IVIG were given after each session of CP. Alternate day CP and hemodialysis were done. After nine sessions of CP, the anti-B blood group antibody titer reached eight and the patient underwent transplant. She received anti-thymocyte globulin induction (1.5 mg/kg/dose on the day of transplant and postoperative day 2). Intravenous methylprednisolone (500 mg) was given intraoperative. Oral prednisolone (40 mg) was started from postoperative day 1 and tapered to 20 mg on discharge. Serum creatinine on discharge was 1 mg/dl [Figure 1]. Her post-transplant course so far has been uneventful with no episode of infection or rejection. Hepatitis C virus RNA level done at 3 months posttransplant was negative. A protocol biopsy done at 7 months posttransplant showed normal graft morphology except for positive C4d staining on immunofluorescence, which is usually seen in cases of ABOi transplants due to accommodation [Figure 2]. Repeat single-antigen bead tests done at 1 and 6 months showed stable donor-specific antibodies (DSAs) [Table 2]b. At the end of 1 year follow-up, she had a good graft function with a serum creatinine of 1.2 mg/dl and no proteinuria.
|Figure 1: Preconditioning and transplantation timeline. MMF: Mycophenolate mofetil, MP: Methylprednisolone, CP: Cascade plasmapheresis, HD: Hemodialysis, ATG: Anti-thymocyte globulin|
Click here to view
|Figure 2: Protocol biopsy at 7 months showing normal morphology by light microscopy and positive C4d staining on immunofluorescence|
Click here to view
| Discussion|| |
Highly sensitized ESRD patients or those with blood group O tend to accumulate on the deceased donor as well as PKE list. Living donor transplantation after desensitization has been shown to provide a significant survival advantage for patients with HLA sensitization, as compared with waiting for a compatible organ despite the higher rate of acute antibody-mediated rejections., Outcomes of ABOi transplants are at par with compatible transplants.
A Korean nationwide cohort study by Ko et al. showed that biopsy-proven acute rejections (BPAR) were higher in HLAi and ABOi + HLAi group compared to ABOi and control group of compatible transplants. The authors concluded that HLAi transplantation was more important risk factor for BPAR than ABOi. Hence, careful selection of a donor against whom the prospective has least number and strength of donor-specific anti-HLA antibodies is important
In our patient, we had to choose between the maternal aunt and the mother as donor. Although the maternal aunt was a blood group compatible donor, the recipient had multiple antibodies against her class 1 and 2 HLA antigens leading to a positive B and T cell crossmatch. While the mother was a blood group incompatible donor there was only class 2 antibodies against her and that too of lower strength when compared to the aunt. Hence, the flow crossmatch showed weak positivity for T cell and positivity for B cell. The outcome in such a case will be better with the donor against whom a recipient has lesser sensitization despite the added factor of ABO incompatibility. The driving factor will be HLA incompatibility and so the donor should be chosen against whom the recipient has lesser number of donor-specific anti-HLA antibodies and of lower strength. Hence, the mother was chosen as the donor and the patient had a good posttransplant outcome so far.
Concluding, appropriate donor selection is important in dealing with highly sensitized recipients. It requires extensive immunological workup pretransplant and close follow-up and monitoring in the posttransplant period. The patient should be counseled for the need of regular DSA monitoring and need of protocol biopsy depending on the center protocol. While selecting the donors opt for the one against whom the prospective recipient is least sensitized.
Declaration of 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, initials would not be published, and all standard protocols will be followed to conceal their identity.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Karpinski M, Knoll G, Cohn A, Yang R, Garg A, Storsley L. The impact of accepting living kidney donors with mild hypertension or proteinuria on transplantation rates. Am J Kidney Dis 2006;47:317-23.
Roodnat JI, van de Wetering J, Claas FH, Ijzermans J, Weimar W. Persistently low transplantation rate of ABO blood type O and highly sensitised patients despite alternative transplantation programs. Transpl Int 2012;25:987-93.
Marfo K, Lu A, Ling M, Akalin E. Desensitization protocols and their outcome. Clin J Am Soc Nephrol 2011;6:922-36.
Montgomery RA, Lonze BE, King KE, Kraus ES, Kucirka LM, Locke JE, et al
. Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med 2011;365:318-26.
de Weerd AE, Betjes MGH. ABO-incompatible kidney transplant outcomes: A meta-analysis. Clin J Am Soc Nephrol 2018;13:1234-43.
Ko EJ, Yu JH, Yang CW, Chung BH, Korean Organ Transplantation Registry Study Group. Clinical outcomes of ABO-and HLA-incompatible kidney transplantation: A nationwide cohort study. Transpl Int 2017;30:1215-25.
[Figure 1], [Figure 2]
[Table 1], [Table 2]