Dear Editor, ABO-incompatible (ABOi) renal transplantation with baseline isoagglutinin titer >1:256 is considered high, with challenging outcomes.1 We present a successful ABOi transplant with baseline titer 1:1024 (gel card technique), managed using rituximab, bortezomib, and immunoadsorption. Our patient was a 33-year-old man with IgA nephropathy on maintenance hemodialysis for 3 years. He consented to an ABOi renal transplant with his father (blood group A1 +ve) as donor, while the patient was O +ve. His baseline isoagglutinin titer was 1:1024, with a haploidentical match, negative complement-dependent cytotoxicity, negative flow crossmatch, and negative single antigen bead assay for Class 1 and Class 2 antibodies. He received 200 mg rituximab 14 days pretransplant. After 1 week, the titer remained 1:1024. The patient started tacrolimus (0.07 mg/kg), mycophenolate sodium (360 mg TID), and steroids (0.5 mg/kg) 14 days before transplantation. CD 20 B-cell percentage was 0.04%, indicating B-cell suppression. He received bortezomib (2 mg) 5 days pretransplant. His titer before immunoadsorption (Glycosorb® anti-A column) was 1:512. He underwent hemodialysis followed by immunoadsorption for 14 h with heparin, monitoring aPTT, INR, and anti-A titers every 4 h. Heparin was stopped 4 h pretransplant at titer 1:16. Immunoadsorption was continued until titers reached 1:8. Intraoperatively, methylprednisolone (1 g) and anti-thymocyte globulin (1 mg/kg) were given. The graft became turgid postanastomosis with good urine output. Anti-A titer reached 1:64 on post-operative day 1 (POD1), requiring repeat immunoadsorption. Normal renal function was achieved on POD2, with creatinine 0.9 mg/dl, and titers remained stable at 1:32. Tacrolimus levels were maintained at 5–8 ng/ml. A rebound titer of 1:128 on POD10 was managed with immunoadsorption and 3 cycles of plasma exchange. The patient was discharged on POD17 with creatinine 1.2 mg/dl and titer 1:32. He was on standard post-transplant prophylaxis of valganciclovir 450 mg/day and cotrimoxazole 480 mg/day at discharge. He maintained normal renal function (creatinine – 1.1 mg/dl) at 5-month follow-up without any infection risk. This case highlights combining rituximab, bortezomib, and immunoadsorption cost-effectively. Rituximab, an anti-CD20 monoclonal antibody, at 200 mg doses sufficiently suppresses B cells with reduced infection in ABOi renal transplantation.2 The presence of high ABO antibody titers >1:512 (our patient − 1:1024) is at a very high risk of antibody-mediated rejection and graft loss, leading to inferior transplant outcomes, justifying the use of aggressive immunosuppression in the background of negative anti-human leukocyte antigens antibodies.1,3 Bortezomib, a proteasome inhibitor with 40–193 h half-life, arrests short- and long-lived plasma cells,3 reducing antibody burden when given 3–5 days before transplantation. Rituximab administration should occur 2 weeks before transplantation to deplete mature B cells.4 The utility of Bortezomib is justified considering that bortezomib is the only commercially available treatment option that leads to plasma cell apoptosis and inhibits future alloantibody production in this high ABO antibody titer background.3 We performed a 14-h immunoadsorption with patient consent to reach acceptable anti-A titers, followed by repeat immunoadsorption on POD1 and POD 10 using the same ethylene oxide-sterilized cartridge.4 We utilized the physiological concept of a large surface area combined with the surface porosity of the immunoadsorption cartridge to operate for 14 h, which led to the anticipated reduction in antibody levels. Utilizing immunoadsorption cartridges multiple times lowers the costs associated with managing antibody rebound, while not impacting other immunoglobulins or compromising patient safety. This treatment reduced ABOi renal transplantation costs to INR 10–11 lakhs, including medications, consumables, transplant, and procedure costs. The cost of plasma exchange is around Rs. 40,000–50,000/session, and a titer of 1:1024 may entail a minimum of 7–8 plasma exchanges, which would cost around Rs. 2.8 lakhs–4 lakhs. The immunoadsorption cartridge costs approximately 2.7 lakhs with the potential of three reuses with ethylene oxide sterilization, entailing a total cost of 3 lakhs and repeat reuse procedural cost amounting to Rs. 10,000. The cost of bortezomib is approximately Rs. 2500/2 mg vial. Hence, a superior modality of immunoadsorption combined with bortezomib is economically comparable to the standard plasma exchange therapy used in ABO-incompatible transplantation. The Indian work group also recommends immunoadsorption if the initial titer is greater than 1:128 or if there is a requirement for more than four plasma exchanges.4 Due to limited data on cartridge reuse safety4 and antibody removal kinetics, we limited treatment to three immunoadsorption cycles. There are no long-term data on the risk of post-transplant infections, graft rejection, or graft loss by the adoption of a bortezomib-based regimen with immunoadsorption versus standard plasma exchange plus rituximab treatment in the present medical literature. This regimen may be adopted in low- to middle-income countries for ABOi renal transplantation, pending further validation on case-to-case basis. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Authors contribution The author was responsible for the conception, design, visualization, investigation, drafting of the text, sourcing, and editing of clinical images, investigation results, critical revision of important intellectual content and final approval of the manuscript. Data availability statement The data for substantiating the findings of this study are available with the corresponding author and can be made available on request. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Gerry George Mathew (Thu,) studied this question.