What Are Eplets in Kidney Transplants? How Eplet Matching Can Help You Get the Best Possible Transplant Outcome
If you have been diagnosed with kidney failure and are considering a kidney transplant, you’ve probably heard a lot about matching, such as blood type, tissue type, or antibodies. One word you may not be familiar with is “eplets.”
Just like blood and tissue type, eplet matching plays an important role in kidney transplants—how well the donor’s eplets match the recipient’s can significantly affect how long the transplant lasts.
How Are Kidneys Matched?
Before we talk about eplets, let’s review how kidneys have been matched in the past. Historically, matches were made by comparing human leukocyte antigens (HLA): genes specific to human beings that you get from your parents. A six out of six antigen match (most common with identical twins and some full siblings) was considered the best, while a zero out of six antigen match was not as good, but still better than staying on dialysis.
Antigen matching has been the standard for determining donor-recipient compatibility for many years, but now there is a better, more accurate way that is based on eplets.
What Are Eplets?
Just as atoms are made up of many smaller components, antigens are composed of smaller units. These smaller units are called eplets.
Eplets are tiny parts of proteins found on the surface of your cells. When you undergo a kidney transplant, your immune system investigates the donor kidney to see if it looks “foreign.” If your body spots too many unfamiliar eplets, your immune system may see the kidney as a threat and start attacking it. This can lead to organ rejection, which may shorten the life of the transplant—or could even cause it to fail.
By comparing the eplets on your cells with those on a donor kidney, doctors can look for a “low eplet mismatch”—in other words, a kidney that looks more familiar to your immune system. The fewer mismatched eplets, the lower the risk that your body will create antibodies against the new kidney.
The Advantages of a Low Eplet Mismatch Kidney Transplant
Eplet matching has several key benefits:
Reduced risk of rejection: After the first year of transplant, 63% of graft failure cases (when the transplanted kidney stops working either partially or completely) are caused by rejection . This happens when a patient’s immune system attacks what it sees as a foreign body—the transplanted kidney (or graft). It does this by forming de novo DSA (new antibodies), which target the transplanted kidney and can cause the transplant to fail. The fewer the eplet mismatches between the donor and the recipient, the lower the chance that de novo DSA will form, and the more likely the transplant will last a lifetime.
Lower immunosuppression medication: With a low eplet mismatch, it may be possible to safely lower the dose of immunosuppressive medications after transplant. This can help reduce unwanted side effects such as increased risk of infection, loss of appetite, nausea, vomiting, diabetes mellitus, hair loss, and hand tremors.
Low Eplet Mismatch Transplants and the National Kidney Registry
The National Kidney Registry (NKR) is a pioneer in low eplet mismatch transplants. In 2020, the NKR launched Kidney for Life, which uses advanced matching technology that incorporates state-of-the-art eplet mismatch analysis.
According to the NKR’s 2025 Outcomes Report:
- Individuals who received a kidney with a medium to high eplet mismatch were much more likely to develop harmful antibodies (de novo DSA) within three years of their transplant (up to 538% higher risk than with a low eplet mismatch).
- Patients who received a low eplet mismatched kidney had a significantly lower rate of de novo DSA formation, which is the precursor of rejection and graft failure.
- Of patients who achieved a low eplet mismatch transplant through the NKR’s Kidney for Life initiative, only 1% showed de novo DSA formation one year post-transplant, compared to 18% for high eplet mismatch patients.
How Can You Get a Low Eplet Mismatch Kidney Transplant?
Eplet matching is a relatively new approach in transplantation, but it is growing. The NKR facilitated 386 low eplet mismatch transplants in 2024, up from 11 in 2020.
If you register as a kidney patient through the NKR and choose a transplant center that participates in the Kidney for Life program, you may be able to achieve a lower eplet mismatch, reducing your chances of rejection and helping your transplant last longer.
While the Kidney for Life initiative is an excellent option for incompatible donor-recipient pairs, it is also available to kidney patients with a compatible donor.
Almost every match can be improved: “perfect” matches (six out of six antigen matches) are very rare, occurring in less than 1% of cases with unrelated donors. Even if you have a compatible donor, you can still participate in an NKR paired exchange. In this program, a donor gives a kidney to another recipient in exchange for a better-matched kidney—often with a lower eplet mismatch—for their loved one. In 2024, 314 donor-recipient pairs (264 with a medium eplet mismatch and 50 with a high eplet mismatch) entered an NKR paired exchange to obtain a low eplet mismatch transplant.
Eplet matching is a new and powerful tool in kidney transplantation, helping doctors find better matches for patients to reduce the risk of rejection. If you’re getting ready for a transplant—or even if you already have a donor lined up—it’s worth talking to your transplant team about participating in an NKR swap to find the best possible match.
Want to learn more about NKR swaps or eplet matching? Talk to your transplant center or visit https://www.kidneyforlife.com for more information.