When a person requires a kidney transplant, a thorough biological assessment is necessary to ensure the best possible outcome. Transplantation is a life-saving procedure for individuals with end-stage renal disease. The body’s immune system naturally views the new organ as a foreign invader, so careful matching must occur between the donor and the recipient. This compatibility process is multifaceted, involving several distinct biological hurdles that must be cleared to allow for long-term graft survival.
Blood Type Compatibility (ABO)
The first requirement for kidney donation is compatibility within the ABO blood group system. The rules for organ compatibility mirror those for blood transfusions, where specific antigens on the surface of red blood cells determine the blood type. If a recipient receives a kidney from an incompatible ABO blood type, the immune system will recognize the organ’s antigens as foreign and immediately launch an attack.
People with blood type O are considered universal donors because their cells lack A and B antigens, making their organs compatible with all other blood types. Conversely, individuals with blood type AB are universal recipients. ABO compatibility is a mandatory starting point, but successfully passing this initial screen does not guarantee immunological acceptance. The Rh factor is not a factor in kidney matching.
Genetic Tissue Typing (HLA)
Beyond blood type, a complex compatibility check involves Human Leukocyte Antigens (HLA), which are proteins found on the surface of most cells. These antigens act like a biological identification tag, signaling to the immune system whether a cell belongs to the body or is a foreign threat. The HLA system is the most variable set of genes in the human genome, meaning it is highly unlikely for two unrelated people to have a perfect match.
The immune system’s reaction to a transplanted organ is dictated by the degree of difference in HLA markers. Typing focuses on six major markers, three inherited from each parent, located at the A, B, and DR loci. Transplant centers assess the number of mismatches across these six antigens, aiming for a lower number, with a perfect match being zero out of six.
A closer match, such as 0/6, significantly lowers the risk of rejection and often allows for lower doses of immunosuppression medication. Minimizing the HLA mismatch remains a goal, particularly for a first transplant, because long-term success is tied to genetic compatibility. However, due to highly effective anti-rejection drugs, successful transplants are common even when a donor and recipient have a full 6/6 mismatch.
Crossmatching and Antibody Screening
Even if the blood type and HLA markers are favorable, a final immunological barrier exists in the form of pre-formed antibodies. The recipient’s body may have become “sensitized” to foreign tissues through past events like blood transfusions, previous transplants, or pregnancies. This sensitization results in the creation of antibodies that are primed to attack foreign HLA markers.
The Panel Reactive Antibody (PRA) test determines the degree of sensitization by measuring how many HLA types a recipient’s blood reacts against. A PRA score is expressed as a percentage, where a higher number, such as over 85%, indicates a highly sensitized recipient who will be very difficult to match.
The definitive test performed just before the surgery is the crossmatch, which directly checks for the presence of donor-specific antibodies in the recipient’s blood. This test involves mixing the recipient’s serum with donor lymphocytes. If the recipient’s antibodies attack the donor’s cells, the result is a positive crossmatch, indicating a high risk of hyperacute rejection. A negative crossmatch confirms that no problematic pre-formed antibodies are present, giving the final medical clearance for the transplant to proceed.
Options for Incompatible Pairs
When a willing living donor is incompatible with their intended recipient due to ABO or crossmatch barriers, several modern solutions exist. The most common and successful strategy is the Kidney Paired Donation (KPD) program, often called a paired exchange. This logistical solution involves incompatible donor-recipient pairs swapping kidneys with other incompatible pairs to ensure that every recipient receives a compatible organ.
The pairs are entered into a registry where a computer algorithm identifies a chain of exchanges, allowing all individuals to receive a compatible kidney from a stranger. KPD has dramatically increased the number of living donor transplants, providing an immunologically safe path to transplantation for pairs who otherwise could not proceed.
Alternatively, desensitization protocols are medical treatments used to actively reduce or remove the recipient’s antibodies reacting against the donor. These intensive protocols may involve treatments like plasmapheresis, which filters the antibodies from the blood, or the use of specific medications. Desensitization is generally reserved for cases where an incompatible living donor is available but a suitable match through KPD cannot be found. While effective, these protocols require more intense immunosuppression and carry a greater risk compared to a standard compatible transplant.