A case series on ABO -incompatible renal transplantation in a tertiary care hospital, Southern Tamil Nadu

Sakthi Selvakumar

Consultant-Nephrologist, Kauvery Hospital, Cantonment, Trichy, Tamil Nadu

Introduction

Kidney transplantation offers the best long-term outcomes for patients with end-stage kidney disease (ESKD) who are eligible for the procedure. In India, the disparity between organ availability and patient demand is stark, with the majority of transplants relying on living donors due to the limited reach of deceased donor programs. Blood group incompatibility is a major barrier to living donor transplantation, especially in regions like Southern Tamil Nadu and the Cauvery delta, where access to deceased donor organs is further constrained by logistical and geographic limitations.

Historically, ABO-incompatible (ABOi) transplantation was considered a contraindication because of the risk of hyperacute rejection caused by preformed anti-A or anti-B antibodies. These isoagglutinins develop early in life through environmental exposure and are directed against blood group antigens expressed not only on red blood cells but also on vascular endothelium. If not adequately removed, they lead to immediate graft loss through complement-mediated antibody-mediated rejection (ABMR) [1,2].

Desensitization protocols—originally involving splenectomy and therapeutic plasma exchange (TPE)—have since evolved to include rituximab, IVIG, and various forms of immunoadsorption. While TPE remains the most commonly used strategy in India, it is non-selective, resulting in loss of albumin, clotting factors, and beneficial immunoglobulins, thus increasing infection and bleeding risk [3,4]. Furthermore, the procedure is often prolonged, requires replacement fluids, and may need to be repeated multiple times.

Glycosorb® ABO immunoadsorption columns (Glycorex Transplantation AB, Sweden) provide a more targeted approach. These columns are coated with synthetic A or B antigens that selectively remove the corresponding isoagglutinins without depleting other plasma proteins or necessitating volume replacement. Their antigen-specific mechanism makes them more efficient and safer in certain settings, with reported outcomes in Europe and Japan comparable to those of ABO-compatible transplants [5,6].

Despite their global adoption, the use of Glycosorb® columns in India remains very limited due to cost and availability. Few centers have reported their use, and there are no prior documented cases of successful ABOi transplants using Glycosorb® in patients with very high baseline titres (≥1:1024). In most Indian protocols, patients with titres exceeding 1:512 are often deemed unfit for ABOi transplantation or require prolonged conventional desensitization [7,8].

In this case series, we present three patients from Southern Tamil Nadu and the Cauvery delta region with initial anti-A/B titres of 1:1024—a level often considered a threshold of exclusion—who underwent successful ABOi living donor renal transplantation using Glycosorb® antigen-specific immunoadsorption. All patients achieved the target pretransplant titre with a uniform rituximab-based protocol, without the need for conventional plasma exchange or IVIG. To our knowledge, this is the first such series reported from this region, demonstrating both the technical feasibility and the short-term safety of using Glycosorb® columns even in recipients with extremely high immunologic risk.

Methods

This is a retrospective case series describing three adult patients with end-stage kidney disease who underwent ABO-incompatible (ABOi) living donor renal transplantation at our center in Southern Tamil Nadu between [Month, Year] and [Month, Year]. All patients had a baseline anti-ABO isoagglutinin titre of 1:1024 and were desensitized using Glycosorb® antigen-specific immunoadsorption (IA) columns in combination with rituximab and standard immunosuppression.

Eligibility and Work-up

All patients had:

  • Confirmed blood group incompatibility with their respective donors.
  • Negative complement-dependent cytotoxicity (CDC) and flow cytometry crossmatches.
  • No donor-specific HLA antibodies (DSAs).
  • Normal cardiac and infectious disease clearance pre-transplant.

Donors and recipients underwent full HLA typing. Transplants were performed only after achieving a pre-transplant anti-ABO titre of ≤1:8, as measured by the conventional tube agglutination method.

Desensitization Protocol

The desensitization protocol included:

  1. Rituximab (375 mg/m²) administered as a single intravenous dose 2–3 weeks prior to the planned date of transplant.
  2. Oral immunosuppression (tacrolimus 0.1–0.15 mg/kg/day and mycophenolate mofetil 720–1,000 mg/day) initiated 10–14 days before transplant.
  3. Glycosorb® immunoadsorption sessions commenced 1–5 days prior to surgery, depending on individual response to rituximab. IA sessions were performed using A or B antigen-specific columns, depending on the donor blood group.

The number and duration of IA sessions were based on baseline titre and monitored using post-session antibody titre measurements. Each session processed approximately 2.5–3 plasma volumes over 3–4 hours, aiming for stepwise halving of titres with each session. No albumin or plasma replacement was required.

Repeat titres were done after each session, and the transplant was scheduled within 12–24 hours of achieving the target titre (≤1:8). Rebound titres were managed with additional IA sessions when needed.

Surgical and Immunosuppressive Management

All patients underwent open living donor renal transplantation with ureteric stenting. Intraoperative and postoperative fluid management followed a standardized protocol with central venous pressure (CVP) and urine output–guided hydration.

Induction immunosuppression included either:

  • Antithymocyte globulin (ATG) 1.5–2 mg/kg total dose in high immunologic risk (rebound titres, strong HLA mismatches), or
  • Basiliximab 20 mg on day 0 and day 4.

Maintenance immunosuppression consisted of tacrolimus (target trough: 8–10 ng/mL), mycophenolate mofetil (1–2 g/day), and prednisolone.

Monitoring and Follow-up

  • Anti-ABO titres were measured daily from the day of admission through day 10 post-transplant, and then on alternate days up to day 14.
  • Serum creatinine was monitored daily until discharge and subsequently during outpatient follow-up.
  • Patients were assessed for signs of rejection (clinical and biochemical). Biopsy was reserved for unexplained graft dysfunction or suspected ABMR.

Prophylaxis included valganciclovir (CMV), cotrimoxazole (Pneumocystis jirovecii), and isoniazid (TB).

Preparing a Patient for ABO-Incompatible Kidney Transplantation

The following steps were followed as part of our center’s standardized ABO-incompatible transplant preparation protocol:

1. Confirm Compatibility and Risk Profile

  • Blood group typing for both donor and recipient, including A1 vs A2 subtyping if relevant.
  • Anti-A or anti-B isoagglutinin titres measured using conventional tube agglutination.
  • Crossmatch testing: CDC and flow cytometry T- and B-cell crossmatches performed.
  • HLA typing and donor-specific antibody (DSA) screen using Luminex single antigen bead (SAB) assay.

2. Eligibility Criteria

  • Absence of DSAs with MFI <1500.
  • CDC and flow cytometry crossmatch negative.
  • Anti-A/B IgG titre ≤1:1024.
  • No active infection or significant comorbidity prohibiting transplantation.

3. Desensitization Timeline

  • Day –21 to –14:
    • Rituximab 375 mg/m² IV infusion with premedication (e.g., hydrocortisone and antihistamines).
    • Start tacrolimus (0.1–0.15 mg/kg/day in 2 divided doses) and mycophenolate mofetil (720–1000 mg/day).
    • Monitor tacrolimus trough (target: 8–10 ng/mL pre-transplant).
  • Day –5 to –2:
    • Begin Glycosorb® immunoadsorption sessions depending on baseline titre.
    • IA performed daily or on alternate days until target titre (≤1:8) is achieved.
    • Titre measured before and 2–4 hours after IA sessions to assess response.
  • Day –1:
    • Final IA session and last titre measurement.
    • Hemodialysis if patient is on MHD.
    • Stop ACE inhibitors or ARBs to avoid allergic reactions with sepharose matrices.

4. Day 0 (Transplant Day)

  • Proceed with transplantation if:
    • Final anti-A/B titre is ≤1:8.
    • No active infections.
  • Administer induction immunosuppression:
    • ATG 1.5–2 mg/kg total over 2–3 days (high-risk or rebound titres)
    • or Basiliximab 20 mg IV on day 0 and day 4 (low-risk).

5. Post-Transplant Monitoring

  • Daily anti-A/B titres until post-op day 10, then alternate days till day 14.
  • Monitor for titre rebound or graft dysfunction. IA is repeated if titres rise to ≥1:16 with clinical suspicion.
  • Serum creatinine monitored daily, and imaging/biopsy done as needed.
  • Start prophylaxis: Valganciclovir, Cotrimoxazole, Isoniazid.

Case Presentation

Case 1

A 27-year-old male (blood group O) with CKD-5 and hypertension underwent ABO-incompatible renal transplantation with his 59-year-old mother (blood group B) as the donor. His baseline anti-B isoagglutinin titre was 1:1024. He received a single dose of rituximab (200 mg) three weeks prior to surgery and underwent three sessions of plasmapheresis using Glycosorb®-B columns until his titre dropped to 1:8. The left kidney, which had a single artery and vein, was successfully anastomosed to the external iliac vessels.

His post-transplant creatinine fell steadily without any episodes of delayed graft function or rejection. Titres remained <1:8 postoperatively, and no rebound was observed. The patient was discharged on POD 8 with stable graft function and eGFR of 86 mL/min/1.73m².

Tacrolimus was increased to 9 mg/day and later titrated to 10 mg/day. He later developed sepsis with elevated procalcitonin; MMF was withheld and he was treated with meropenem and vancomycin. He showed clinical improvement and was discharged on POD 7.

Case 2

A 26-year-old male (blood group O), weighing 53 kg, underwent ABO-incompatible transplantation with his 54-year-old mother (blood group B) as the donor. His anti-B titre was 1:1024 at baseline. He received 375 mg/m² rituximab two weeks prior to transplant and required five sessions of Glycosorb®-B IA to reach a titre of 1:4. He received ATLG for induction and was maintained on tacrolimus, MMF, and steroids.

His post-transplant creatinine fell steadily without any episodes of delayed graft function or rejection. Titres remained <1:8 postoperatively, and no rebound was observed. The patient was discharged on POD 8 with stable graft function and eGFR of 86 mL/min/1.73m².

Case 3

A 59-year-old male (blood group O) underwent ABO-incompatible renal transplantation with his 52-year-old wife (blood group A) as donor. The baseline anti-A titre was 1:1024. He received a single 375 mg/m² dose of rituximab and underwent four sessions of Glycosorb®-A immunoadsorption.

Despite achieving target titres, he experienced titre rebound on POD 5 (1:4 → 1:16), and a fifth IA session was performed. A second rebound on POD 10 (1:32) prompted a sixth session, after which titres stabilized. Creatinine declined steadily; no biopsy was needed, and he remained hemodynamically stable. The patient was discharged on POD 14 with a creatinine of 1.2 mg/dL.

Clinical Cases

Fig. (1):  displays the anti-A/B isoagglutinin titres for the three patients at key time points—baseline screening, post-rituximab, pre- and post-immunoadsorption (IA) sessions, and during the post-transplant period.

Patient 1: had a baseline anti-B titre of 1:1024. Following rituximab, the titre dropped significantly and further decreased to 1:4 after the first IA session. No rebound was observed, and no additional IA was required. Creatinine declined steadily, and he maintained stable graft function post-discharge.

Patient 2: showed a paradoxical increase in titre post-rituximab, with minimal response. He required five IA sessions to achieve a target titre of 1:4. A transient titre rebound occurred post-IA, necessitating a second session on the morning of surgery. Post-transplant titres remained ≤1:8. He experienced a ureteric complication requiring a percutaneous nephrostomy on day 9, but renal function recovered fully with a latest eGFR of 47 mL/min/1.73m² at 5 months.

Patient 3: also had a baseline titre of 1:1024. Although his titre decreased slightly prior to rituximab, there was no additional drop afterward. He underwent four IA sessions pre-transplant and experienced titre rebounds on days 5 and 10 (1:4 → 1:16 and then 1:32), which were controlled with additional IA sessions. He also developed a ureteric stricture requiring nephrostomy and stenting. At 3 weeks post-transplant, his eGFR was 57 mL/min/1.73m².

Fig. (2): illustrates serum creatinine levels post-transplant, showing progressive improvement in all three patients. No patient experienced delayed graft function. Patient 1 had the most rapid creatinine normalization, with a level of 1.2 mg/dL by POD 7. Patient 3 had stable renal function but a slightly delayed nadir due to post-operative complications.

No patient required biopsy for suspected rejection after discharge. All patients were discharged on triple prophylaxis: valganciclovir for CMV, isoniazid for tuberculosis, and cotrimoxazole for Pneumocystis jirovecii.

Discussion

Our early experience with ABO-incompatible living donor kidney transplantation using Glycosorb® immunoadsorption columns demonstrates that this strategy is feasible, effective, and well-tolerated even in recipients with very high baseline anti-ABO titres (1:1024). To our knowledge, this is the first reported case series from Southern Tamil Nadu and the Cauvery delta region documenting the successful use of Glycosorb® in such high-titre patients.

All three recipients in our series were desensitized using antigen-specific Glycosorb® columns following a single-dose rituximab-based protocol. The number of IA sessions ranged from three to six, and the patient with the most persistent rebound (Jayapal) required the highest number of sessions. Notably, rebound of titres was observed in two patients, a phenomenon well-described in ABO-incompatible transplantation, likely due to equilibration between extravascular and intravascular compartments. This rebound pattern has also been reported with conventional plasma exchange.

Despite high immunological risk, none of the patients experienced hyperacute rejection. Only one patient (Niyas) had biopsy-proven acute antibody-mediated rejection (ABMR), which responded to standard treatment including additional IA and IVIG. Two patients developed ureteric complications, both managed with percutaneous nephrostomy and stenting. Creatinine trends showed progressive and sustained improvement in all three cases, with latest eGFRs ranging from 47 to 87 mL/min/1.73m².

Routine monitoring of anti-A/B titres was discontinued after 14 days post-transplant, in accordance with established understanding that titres beyond this period do not correlate reliably with graft dysfunction. This is attributed to a phenomenon called accommodation, wherein the graft becomes resistant to antibody-mediated injury despite persistent or rising titres. As described by Platt and Cascalho, the mechanisms likely involve endothelial adaptation, decreased antigen accessibility, and modulation of antibody characteristics [11].

C4d positivity alone on biopsy—if seen—should not prompt treatment in the absence of clinical or histological features of rejection. Our center does not perform protocol biopsies solely for the purpose of identifying accommodation, but recommends close monitoring of graft function and titres.

Although rare, late ABMR can still occur, often triggered by systemic inflammatory states such as sepsis. It has been hypothesized that polyclonal IgM production during such episodes may reactivate antibody responses to ABO antigens [12].

Based on our experience, candidates for this type of transplant should meet the following criteria:

  • No available ABO-compatible living donors.
  • Absence of significant HLA sensitization (e.g., low or absent DSA).
  • Acceptable cardiopulmonary risk profile and transplant fitness.
  • Baseline anti-A/B titres ≤1:1024, recognizing that even very high titres may be manageable with targeted IA therapy.

In selected patients, particularly those lacking deceased donor access or facing prolonged dialysis dependency, Glycosorb®-based desensitization offers a viable and safe alternative, even in challenging immunologic scenarios. While the cost of IA columns remains a barrier in many Indian settings, this approach may yield downstream savings by reducing complications associated with conventional PLEX and prolonged hospital stays.

Conclusion

This small but significant case series demonstrates that ABO-incompatible living donor kidney transplantation using Glycosorb® immunoadsorption columns is both feasible and effective, even in patients with very high baseline isoagglutinin titres (1:1024). All three patients in our series achieved successful desensitization and stable post-transplant graft function with no early mortality or graft loss.

In resource-limited settings like Southern Tamil Nadu, where access to deceased donor transplantation remains low and many patients lack compatible living donors, Glycosorb®-based desensitization offers a viable solution for expanding transplant eligibility. While the upfront cost of the immunoadsorption columns remains a concern, the procedure is relatively simple to implement—requiring only rituximab, isoagglutinin monitoring, and targeted IA sessions—and may ultimately reduce long-term dialysis-related expenses.

With proper patient selection and close post-transplant monitoring, this approach has the potential to improve transplant access and outcomes for highly sensitized patients in both public and private sector transplant programs across India.

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