For people with end-stage chronic kidney disease in South Africa, deceased donor organ transplant has, until now, been seen as the only potential lifeline, but now ABO-incompatible kidney transplantation has increased survival chances.
In the SA Medical Journal, nephrologist Zunaid Barday writes that ABO-incompatible kidney transplantation gives patients with chronic kidney disease requiring dialysis and without a blood group-compatible donor an alternative option.
He discusses using Glycosorb ABO immunoadsorption (IA) columns in performing ABO-incompatible living-donor kidney transplants on three patients – the first time this technique has been used in Africa.
He writes:
Kidney transplantation provides the best long-term outcomes for patients with end-stage chronic kidney disease who are well enough to receive a kidney transplant but the shortage of deceased donor organs worldwide, and especially in South Africa – deceased-donor donation rates here are among the lowest in the world – means living kidney donation options need to be more actively explored.
Unfortunately, sometimes patients don’t have a living-donor option, often having no relatives or friends offering to donate, while many who do are not suitable or are blood group or tissue incompatible.
Blood group incompatibility has long been an absolute barrier to organ transplantation, because blood group antigens are not only expressed on red blood cells but on almost all cells in the body, including endothelial cells. Preformed anti-A or anti-B (or both) isohaemagglutinin antibodies develop soon after birth in all humans who do not have the cognate blood group, even without prior blood transfusions.
These isohaemagglutinin antibodies are thought to result from contact with A- and B-like antigens in the intestines from exposure to various nutrients and bacteria, and almost always induce hyperacute antibody-mediated rejection (ABMR) if present in a recipient transplanted with an ABO-incompatible organ, resulting in very poor graft outcomes.
Back in the late 1980s, techniques were developed to overcome this phenomenon, initially involving splenectomy and plasma exchange to reduce the titres of these isohaemagglutinin antibodies to a level that would allow safe transplantation.
Subsequently, it was found that rituximab, an anti-CD20 monoclonal antibody that triggers destruction of B cells (which produce antibodies), could be safely substituted for splenectomy.
In the early 2000s, Glycorex Transplantation AB, a Swedish health technology company, developed an immunoadsorption (IA) column (IAC) with the brand name Glycosorb ABO. The three different specificity columns remove either anti-A or anti-B isohaemagglutinin antibodies, or both simultaneously if needed.
The columns contain synthetic terminal trisaccharide A or B (or both) blood group antigen covalently bound to a Sepharose matrix. During the IA procedure, plasma is separated from the other blood constituents in the same way as with plasma exchange (via filtration or centrifugation), but then instead of the plasma being discarded, as would be the case with plasma exchange, it is passed through the Glycosorb IAC, where the specific anti-A or anti-B (or both) isohaemagglutinin antibodies are bound.
After passing through the IAC, the plasma is returned to the patient. Insignificant amounts of other antibodies or proteins are removed, and no replacement solution like albumin or fresh-frozen plasma (FFP) is required.
These IACs have been used successfully in more than 6 000 patients throughout the world, but not in Africa.
First in SA
The first use in an ABO-incompatible kidney transplant recipient took place at Groote Schuur Hospital early in 2023. Subsequently two more have been performed at UCT Private Hospital.
More ABO-incompatible living-donor transplants are planned at both hospitals in the coming months.
Since our first case at Groote Schuur Hospital was publicised, there has been strong interest from both patients on dialysis and their treating nephrologists, as well as from healthcare funders couuntrywide, regarding this technique.
The key elements, from our first three patients using Glycosorb ABO IACs to allow safe kidney transplantation from ABO-incompatible living donors include: (i) anti-A/B isohaemagglutinin titre measurement; (ii) B-cell depletion using rituximab; and (iii) antibody depletion – ideally done with an IAC.
Clinical cases
Patient 1 was 35 and had been on haemodialysis and on a deceased-donor waiting list for nine years, as she had no blood group-compatible living-donor options. She was blood group B. Her brother, who was blood group A, was tested to be a potential donor. They were tissue compatible, being haploidentical with only a 3/10 HLA-mismatch and no DSAs, and he was therefore worked up as a donor nephrectomy.
Patient 2 was 68, a blood group O dialysis patient who had been on haemodialysis for one year. He had no willing living-donor options except for his ABO-incompatible wife. She was blood group A, and they were tissue compatible with an 8/10 HLA-mismatch and no DSAs.
Patient 3 was 40 and had developed ABMR two years after her first kidney transplant and soon after giving birth to her child. Despite plasma exchange, her graft failed. She had been back on haemodialysis for almost three years. She had a sister who had never been tissue typed or cross-matched against her, (being blood group incompatible) but she was tested – and while not HLA identical, she was haploidentical and with only a 4/12 mismatch.
The patient only had one strong DSA against the four mismatched alleles and had negative CDC and flow cytometry T- and B-cell crossmatches to her sister.
As per our protocol, blood group A subtyping was done to look for non-A1 blood group, as this can be treated practically as a blood group O donor, making desensitisation unnecessary, unless the recipient has very high anti-A antibody titres. All three donors were blood group A1.
Results
After the procedures, Patient 1 had a significant drop in titre after rituximab and achieved the target level of 1:4 (22) after the first IA session pretransplant, and did not require another session thereafter.
Patient 2 had an increase in titres after screening, which did not decrease after the use of rituximab. He also had a rebound in antibody titre overnight after the first IA session, which necessitated a second IA session on the morning of surgery, but titres remained low thereafter.
Patient 3 had a very high titre at screening of 1:256 (28), which spontaneously decreased before receiving rituximab, but did not decrease further following rituximab. She also did not show a good response to the first IA session and needed a second session on the morning of surgery.
Her titre remained low until day eight8, when it suddenly increased from 1:4 to 1:16 (24) despite her creatinine being at its lowest level since the transplant at 98 μmol/L. She therefore received her third session of IA with titres reducing to 1:8 (23) for two days thereafter, and again needed a fourth session on day 11 when her titre increased to 1:32 (25), but titres subsequently remained at acceptable levels.
All three patients had good responses in terms of graft kidney function.
Patient 2 developed ureteric obstruction, diagnosed on day eight, requiring percutaneous nephrostomy placement on day nine, and subsequently had a complicated urological course, but at the time of writing has good renal function with all the urological issues resolved.
Patient 3 also developed a ureteric stricture, diagnosed on day 13, requiring a nephrostomy the same day. A double-J stent was placed on day 15 and the patient was discharged on day 17 after the nephrostomy was removed.
Neither had a stent placed at the time of transplant.
All of the patients have latest estimated glomerular filtration rates of between 47 and 87 mL/min/1.73 m2 using the CKD-EPI formula (patient 1 at 87 mL/min 6 months post-transplant, patient 2 at 47 mL/min at five months post-transplant, and patient 3 at 57 mL/min at three weeks post-transplant).
No patient required a biopsy to exclude rejection, and all were discharged on prophylaxis against cytomegalovirus (valganciclovir), tuberculosis (isoniazid) and Pneumocystis jirovecii (co-trimoxazole).
As per the protocol, patients needed between one and four sessions of IA and received rituximab ~ one month before transplantation.
All the patients achieved the target isohaemagglutinin antibody titre of 1:4 pretransplant. Only one patient with the highest initial screening titre (1:256) needed IA post-transplant. None of the patients experienced clinical rejection, and all had good graft kidney function at discharge and at the time of writing.
Our first experiences with ABO-incompatible living-donor kidney transplants using Glycosorb IACs have shown that this is an effective technique in allowing ABO-incompatible transplants to be performed successfully in an SA setting
Zunaid Barday MB ChB – Division of Nephrology and Hypertension, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital.
See more from MedicalBrief archives:
Africa’s first incompatible kidney transplant at Groote Schuur
Why I gave my kidney to a stranger — and why you should, too
Less-than-perfect kidneys can be successfully used for transplants
Medical students tackle SA’s organ donation crisis