ABO-Incompatible Kidney Transplant, Swaps and Donor Rules

An ABO-incompatible kidney transplant, in which donor and recipient have different blood groups, can proceed when the recipient's antibody titre against the donor's blood group is below 1:256. In Dr. Shafiq Ahmed's protocol, one dose of rituximab and five sessions of plasmapheresis then bring the titre below 1:32 before surgery. Pairs with higher titres can often swap donors with another incompatible couple.

Blood group mismatch is one of three questions that decide whether a family can go ahead with a living-donor transplant. The other two are whether the law allows this donor to give, and how likely the new kidney is to be rejected. Dr. Shafiq Ahmed, Senior Director - Urology, Andrology & Renal Transplant, BLK-Max Super Speciality Hospital, New Delhi, India, answered all three in the question session of his masterclass for doctors across Africa, along with what the donor and the recipient must do for life afterwards. The surgery itself is covered in the robotic kidney transplant complete guide and the step-by-step account of the robotic kidney transplant procedure.

Who can donate a kidney under Indian law

Under Indian law, the straightforward route for a living kidney donor is a near relative, and a donor who is not a near relative needs prior approval from an authorisation committee. India's transplant law limits living donation to protect donors from being paid or pressured. Dr. Ahmed put its purpose simply: the law exists to keep money out of donation and to protect the donor's interest.

The Transplantation of Human Organs and Tissues Act defines a donor's "near relatives" as the spouse, parents, children, brothers, sisters, grandparents and grandchildren. Of these, the spouse is the only donor who is not a blood relative. For near relatives, the blood relationship is proved by DNA testing performed in the hospital as part of the full screening process.

More distant relatives can also donate. Dr. Ahmed has performed transplants from cousins, uncles and maternal aunts, and from a mother-in-law to her daughter-in-law and a father-in-law to his son-in-law. The condition is proof. For a cousin, that can mean DNA testing across the family to construct a full family tree and show that the two are indeed cousins, which he described as the challenging part. Once the authorities are satisfied that the donation is genuine and not a financial transaction, it can proceed with the authorisation committee's approval.

Two limits matter in practice:

• A brother-in-law is not a blood relative, and Dr. Ahmed said he cannot donate under the standard criteria.
• Donation by a friend or other unrelated person is not a route families can plan on: Dr. Ahmed said he has not seen a transplant authorisation committee grant clearance on that basis, and in practice only related donors are eligible.

What this means for international patients

For patients travelling for a transplant, time is short and the patient is often unwell, so Dr. Ahmed's advice is direct: bring a related donor from the family. Only related donors are eligible, and cousins qualify. A brother, sister, spouse, parent or child proceeds without hassle, while a cousin as donor means bringing full family documentation, completing all the DNA testing and constructing the family tree, and he acknowledged that this is genuinely difficult for international patients. Under the Transplantation of Human Organs and Tissues Rules, every transplant involving a foreign national also requires prior approval from an authorisation committee. The referral pathway, embassy verification and costs for international patients are set out in a separate masterclass article on kidney transplant in India for international patients.

ABO-incompatible kidney transplant: the antibody threshold

When a willing family donor has the wrong blood group, the transplant is still doable, provided the recipient's antibody level against the donor's blood group is low enough. Everyone carries antibodies against the blood groups they do not have. A person with blood group B, for instance, has anti-A antibodies, which would attack a kidney from a group A donor. The question is how much antibody the recipient carries, measured as a titre: the highest dilution of the recipient's blood at which the antibody can still be detected. A titre of 1:256 means a great deal of antibody; 1:8 means very little.

Dr. Ahmed used the example of a married couple in which the wife is group A and wants to donate to her husband, who is group B. The team measures the recipient's antibody titre against the donor's blood group and, in his protocol:

1. Checks the starting titre. If it is below 1:256, the transplant can proceed.
2. Gives one dose of rituximab, a drug that depletes B cells, the immune cells from which antibody-producing cells develop.
3. Performs five sessions of plasmapheresis, a procedure that filters antibodies out of the blood plasma.
4. Confirms the titre has fallen below 1:32 before transplant, ideally to 1:16 or 1:8. Anything below 1:32 is acceptable to proceed.

The two numbers do different jobs. The starting threshold of 1:256 decides whether desensitisation is attempted at all; the target of below 1:32 decides when the operation can go ahead. Above the starting threshold, Dr. Ahmed's route is a swap.

Kidney swap transplant when titres are too high

If the couple's antibody titre is too high, a swap may solve the problem. A kidney swap, or paired exchange, matches two incompatible donor and recipient pairs so that each donor gives to the other pair's recipient. In Dr. Ahmed's example, a couple with high titres would look, often through their dialysis centre, for another pair with the reciprocal mismatch: a recipient who needs a group A kidney but has a group B donor. Each donor then gives to the compatible recipient, and two impossible transplants become two possible ones.

Indian law recognises swaps alongside donation by near relatives. Dr. Ahmed has performed many swap pairs, including around three to four international swaps in which the nephrologist in the referring country made the pairing, matched the compatible donors and confirmed that each couple would donate to the other.

Is kidney donation safe for the donor?

In Dr. Ahmed's experience, a healthy person can donate a kidney to a loved one without problems, and his selection rule is that the donor must be absolutely fit to donate. Public campaigns on organ donation mostly concern deceased donors. Much of the fear around donation, in his experience, comes from a lack of knowledge.

Unlike a liver donor, whose liver regrows, a kidney donor lives with one kidney and must protect it. His guidance for donors:

• Watch the family history. Donors with diabetes or hypertension in the family should check for both regularly.
• Hold an optimal weight and follow a disciplined diet.
• Avoid unnecessary painkillers and antibiotics, which can harm the kidney when taken too often.
• Have an annual check-up. Four simple tests show whether the kidneys are healthy: blood pressure, a urine test for protein, a kidney function test and an ultrasound.

Dr. Ahmed recommends the same annual check to everyone, donors or not, on the principle that no one is healthy until it has been confirmed.

Rejection risk after ABO-incompatible kidney transplant

Asked whether rejection is more likely with an unmatched donor, Dr. Ahmed's answer was that it is no longer the threat it once was. Rejection was very high in the 1990s; today it is far less common, although antibody-mediated rejection remains more frequent after ABO-incompatible transplant than after a compatible one. The change came from immunology. Teams can now identify before surgery which patients will not have a successful transplant and exclude them, using tests such as:

• Virtual crossmatch: comparing the recipient's known anti-HLA antibodies with the donor's tissue type, before any blood is mixed.
• Single-antigen bead testing: identifying exactly which donor tissue antigens the recipient has antibodies against.
• Panel reactive antibody (PRA) testing: estimating how sensitised the recipient is to tissue from the general donor population.

These tests are highly specific and can show whether a kidney will suit a recipient and with what chance of success. The published figures put the difference in proportion:

Even so, the large majority of ABO-incompatible kidneys keep working, and graft survival comes close to that of compatible transplants. His conclusion: rejection is not the major issue in kidney transplant that people believe it to be, whether the transplant is ABO-compatible or not.

How rejection is diagnosed and treated

Rejection after a transplant from an unmatched donor is diagnosed in the same way as after a compatible one, and treatment follows the type of rejection the biopsy shows. Dr. Ahmed's sequence:

1. Watch the trend. The first signs of suspected rejection are a rising creatinine trend and a change in the kidney's urine output.
2. Confirm by biopsy. Kidney biopsy, practised worldwide, is the gold standard test. Non-invasive donor-derived DNA tests, which measure fragments of the donor kidney's DNA in the recipient's blood, are now available in India, though not yet widely used across the world.
3. Give pulse steroids for cellular rejection. First-line treatment of T-cell-mediated rejection is pulse therapy with high-dose steroids. If the response is good, the patient continues on maintenance treatment. Antibody-mediated rejection also needs plasmapheresis, usually with intravenous immunoglobulin, from the outset.
4. Escalate if needed. If the response is poor, second-line treatment is rituximab or plasmapheresis to remove preformed antibodies, chosen according to the condition and managed by the nephrologist.

The first six months after kidney transplant

Dr. Ahmed described the first six months as very crucial in any transplant, because three risks peak together: drug toxicity, infection and rejection. For patients who travel for surgery and return home, continuity of care decides the result. Creatinine levels go up and down during this period. Patients need to:

• check their immunosuppressant drug levels regularly
• maintain extreme hygiene to avoid infection
• stay in touch with the referring physician at home, and keep the transplant team in the loop as well

Tacrolimus levels are kept within predetermined target ranges, adjusted by trial and titration in the early period.

Lifelong immunosuppression, at the lowest effective dose

Beyond six months, visits become less frequent, but blood tests and drug levels must continue, and patients can never fully relax about the health of the kidney. Immunosuppression continues for as long as the kidney works; it is lifelong. What changes is the intensity. Doses fall to the minimum possible and the number of medicines falls too: in Dr. Ahmed's practice, steroids are reduced and eventually stopped, and the antifungals and antibiotics given early on are discontinued. Two drugs remain for the long term, tacrolimus and mycophenolate mofetil, because high doses are no longer needed to prevent rejection after six months. Whether steroids are withdrawn varies between transplant centres, and many keep a low maintenance dose, so the decision rests with each patient's transplant team. Rejection, medication and long-term survival are also covered in a separate article on life after kidney transplant.

The purpose: a return to normal life

For Dr. Ahmed, the measure of all of this is a normal life. After six months, transplant recipients should return to whatever they did before, whether studying, teaching, practising medicine or running a business. That, he said, is what the transplant is for. For nephrologists referring patients, the practical sequence is clear: identify an eligible family donor early, test blood group and antibody titres, consider a swap where titres are too high, and plan shared follow-up for the first six months. The doctors' questions and Dr. Ahmed's complete answers are on the masterclass's Live Discussion page, and the nephrology hub lists related masterclasses.