1. Why Blood Type Alone Is Not Enough for a Transplant
A kidney transplant is an operation in which a healthy kidney from a donor is placed into the body of a person whose own kidneys have failed. The donated kidney can come from someone who has recently died, or from a living person such as a relative or friend [1].
Before the operation, the transplant team looks at whether the patient's immune system is likely to accept the new kidney. Blood type is one factor that can make a wait shorter or longer [1]. The other is HLA, short for human leukocyte antigen. HLA is a set of small proteins found on cells, sometimes called a person's "tissue type" [3]. HLA matching is a genetic test that compares these proteins in two people to see how closely their tissues match [2].
The immune system uses markers like these to tell "me" from "not me." If the patient's immune system recognizes the kidney's HLA as foreign, it may attack the kidney. That attack is called rejection. So how much does a mismatch really matter?
2. How Much Does a Mismatch in HLA Raise the Chance That a Kidney Fails?
A research team led by the US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) looked at kidney transplant data from 1987 to 2013. They studied 189,141 first-time adult transplants in the United States, all with kidneys from donors who had died. Each mismatched pair of tissue proteins was linked to a 13 percent higher risk of the transplant failing, meaning the patient had to go back to dialysis [2]. The NIDDK summary does not say whether this is a relative or an absolute increase, so it is best read as a rough size of the effect, not as a 13-in-100 chance.
That is a statistical result across many people, not a prediction for any one patient. NIDDK also notes that how important HLA matching is, compared with other factors such as the recipient's age and ethnicity, has been debated for many years. The researchers said more study is needed, but that closer matching could help kidneys last longer [2].
If mismatches matter, why are mismatched kidneys ever used? The answer is a group of medicines.
3. What Anti-Rejection Medicines Can and Cannot Make Up For
Anti-rejection medicines, also called immunosuppressants, turn down the immune system so that it does not attack the new kidney. NIDDK says newer drugs have somewhat overcome the effects of tissue mismatch, but they do not remove the need for good genetic matching [2]. This is why a perfect HLA match is not required for a transplant to go ahead.
The medicines have a cost. People with a transplanted kidney take them every day, and MedlinePlus says this continues for the rest of their lives [4]. NIDDK explains that these medicines weaken the immune system, which can lead to infections, and that over long periods this can increase the risk of some cancers. Some of them can also cause other problems, such as high blood pressure or diabetes, in some people [1]. Not everyone has all of these effects, and transplant teams run regular tests to keep watch.
So a better HLA match and the medicines work together. Matching is not the only tool, and the medicines are not a free pass. The next part of the story is about something that can already be inside a patient's body before any kidney is offered.
4. How a Person Can Build HLA Antibodies Before a Transplant
Antibodies are proteins the immune system makes to stick to things it sees as foreign. Some kidney patients already have antibodies against HLA that is not their own. These patients are called "sensitised." NHS Blood and Transplant (NHSBT), the organization that runs organ donation and blood services in the United Kingdom, explains that these antibodies can bind to a transplanted kidney and cause rejection. Patients with many antibodies cannot receive most kidneys, so they may wait many years [3].
Where do the antibodies come from? One route is blood transfusions. Kidney patients often need transfusions, and even a standard red blood cell transfusion contains a small number of white blood cells that carry HLA. If that HLA differs from the patient's, the body can learn to recognize it as foreign. NHSBT says past research suggests that 38 percent of kidney transplant patients develop HLA antibodies after a red blood cell transfusion [3]. That is roughly 4 patients in 10 in those studies, and not a guarantee for any one person.
Pregnancy is another route, because a baby's blood can carry HLA that differs from the mother's, and NHSBT says women can become sensitised this way. NHSBT's programme to give "double matched" blood, matched for white blood cells as well as red ones, aims to prevent these antibodies. In a pilot, patients who received only double matched blood did not make HLA antibodies against their transplanted kidneys [3]. So antibodies are a reason doctors need one more check, which is the next step.
5. How Doctors Test a Kidney and a Patient Together Before the Operation
Comparing HLA types on paper cannot show whether a patient already has antibodies that would attack a particular donor. For that, transplant teams do a cross-match. NIDDK describes it as testing the donor's blood against the patient's blood to help predict whether the patient's immune system will accept or reject the new kidney [1].
Patients on the waiting list also give a blood sample every month, so the center always has a recent one to test against any kidney that becomes available [1]. A kidney from a relative is more likely to be a good tissue match than a kidney from an unrelated person [1].
Taken together, these checks look at different questions. Blood type checks one part of whether a transplant may be suitable. HLA typing asks how similar the tissues are. Cross-matching asks whether this patient's blood reacts to this donor. And what is still unknown?
6. What Doctors Still Argue About When They Match Tissue Types
NIDDK says the importance of HLA matching, compared with factors such as age and ethnicity, has been debated for many years, and that the new study "reinforces the value" of matching for kidneys from donors who have died [2]. Researchers also say that more research is needed.
The studies described here are about kidneys. Nothing in them shows that HLA matters equally for every organ, so this article does not claim that. If you want to compare kidneys with other organs, the original reports are the place to start.
7. A Card Game That Shows Why a Perfect Match Is Hard to Find
Real HLA has many more variations than this game. It only gives a feeling for why exact matches are rare.
Cut paper into 12 small cards. On each card, draw three boxes in a row. Color each box with one of four colors: red, blue, yellow or green. Pick colors at random: for each box, draw one of four colored slips from a bag, then put it back before the next draw. Each card now stands for one person's "markers."
Pick one card as the patient. Search the other 11 cards for one that matches all three boxes. Often there will be none, though sometimes you may find one or more. Then search for a card that matches in at least two boxes. Those are much easier to find. A perfect match is rare, and a partial match is common, which is part of why doctors have to decide how much of a mismatch is acceptable.
If you want to read the original sources, the NIDDK pages about kidney transplants and the 189,141-transplant study are written for the public, and the NHSBT page explains transfusions and antibodies in plain language.