The transplantation of a kidney requires a thorough screening process to ensure the recipient’s immune system does not immediately destroy the new organ. The body’s defense mechanisms attack anything recognized as “non-self,” and a transplanted kidney is foreign tissue. Compatibility testing uses laboratory steps to predict the likelihood of a severe immune reaction, known as rejection. This multi-step screening is performed before a transplant to provide the best chance for the kidney to function long-term.
The First Hurdle: Blood Group Compatibility
The initial step in matching a kidney donor and recipient is confirming compatibility of the ABO blood group system, similar to the requirement for a blood transfusion. Antigens are present on the surface of red blood cells and the cells lining the kidney’s blood vessels. A person’s blood type (A, B, AB, or O) determines which of these antigens they possess.
If a recipient is exposed to a foreign ABO antigen, their body possesses pre-formed antibodies that will launch a rapid immune attack. For example, a person with Type A blood has anti-B antibodies, and a kidney from a Type B donor would face hyperacute rejection. Type O donors are universal donors because their cells lack both A and B antigens.
Conversely, a Type AB recipient is a universal recipient because they lack anti-A and anti-B antibodies, allowing them to accept a kidney from any ABO blood type. While medical advances now allow for desensitization protocols to remove these antibodies, the preferred and safest route remains an ABO-compatible match.
Genetic Blueprint: Understanding HLA Typing
Beyond the ABO blood group, matching involves analyzing Human Leukocyte Antigens (HLA), proteins found on the surface of most cells. These antigens act as identification markers that the immune system uses to distinguish its own cells from foreign invaders. The closer the HLA match, the less likely the recipient’s body is to recognize the kidney as foreign tissue and mount an immune response.
HLA typing focuses on three specific loci: HLA-A, HLA-B, and HLA-DR. Since an individual inherits one set of antigens from each parent, a total of six antigens are analyzed for both the donor and the recipient (two at A, two at B, and two at DR). The goal is to minimize the number of mismatches between these six pairs.
A “perfect match,” where all six antigens align, is rare, usually occurring only between identical twins. Clinicians aim for the lowest possible number of mismatches, as the HLA-DR locus is often considered the most significant for long-term graft survival. Even with several mismatches, a transplant can be successful due to modern immunosuppressive medications.
The Critical Safety Check: The Crossmatch Test
The crossmatch test is the final safety check before a kidney transplant. While HLA typing identifies the genetic potential for a match, the crossmatch determines the actual presence of pre-existing antibodies in the recipient’s blood directed against the donor’s tissue. The test combines the recipient’s serum (containing antibodies) with the donor’s lymphocytes (white blood cells carrying HLA antigens).
If the recipient’s antibodies attack the donor’s lymphocytes, the result is a positive crossmatch. This indicates the recipient’s body would immediately reject the kidney, a severe reaction known as hyperacute rejection, making the transplant unsafe. A negative crossmatch means no significant antibody reaction occurred, indicating the recipient is immunologically safe to receive the kidney.
The recipient’s overall level of sensitization to foreign HLA antigens is measured by the Calculated Panel Reactive Antibody (cPRA) score. This percentage estimates the proportion of the general donor population against whom the recipient has pre-formed antibodies. A high cPRA score (e.g., 80% or 90%) means the recipient is highly sensitized and will likely have a positive crossmatch against most potential donors.
Navigating Incompatibility: Options When the Match Isn’t Perfect
When testing reveals an incompatibility, options exist to overcome these immunological barriers and achieve a successful transplant.
One effective strategy is the Paired Kidney Exchange (PKE), also known as a kidney swap program. This program is designed for living donor pairs who are ABO or crossmatch incompatible. In a PKE, the pair is matched with others in a national registry, allowing the recipient’s donor to give their kidney to a compatible recipient in the exchange chain. The original recipient then receives a compatible kidney from another donor in the chain, resulting in compatible transplants for all involved.
Another pathway is a desensitization protocol, primarily used for ABO-incompatible and certain HLA-incompatible cases. Desensitization involves administering medications and procedures, such as plasmapheresis, to temporarily reduce harmful antibodies in the recipient’s bloodstream before surgery. This procedure removes antibodies that would otherwise attack the kidney, allowing the transplant to proceed. While desensitization carries a higher risk and requires more intensive post-operative care, it provides an option for patients with a willing, incompatible living donor.