Kidney transplantation replaces a failing kidney with a healthy one from a donor for individuals with end-stage renal disease. Success depends fundamentally on the body’s immune system accepting the new organ rather than rejecting it as foreign. A careful process of immunological matching between the donor and recipient is necessary to minimize the risk of immediate organ failure. Traditionally, this required compatible blood types, but advancements now offer pathways to overcome this barrier.
The Necessity of ABO Blood Type Matching
The ABO blood group system is the first compatibility test performed before a kidney transplant. This system is based on specific antigens, or markers, on the surface of red blood cells and kidney tissue. A person’s blood type determines which antigens they have: Type A has A antigens, Type B has B antigens, Type AB has both, and Type O has neither.
The immune system naturally produces antibodies against antigens not present on its own cells. For instance, a person with Type A blood has pre-formed anti-B antibodies. If a Type B kidney were transplanted into a Type A recipient, these antibodies would immediately recognize the foreign B antigens.
This recognition triggers hyperacute rejection, a rapid and severe immune response. The recipient’s antibodies bind to the donor organ’s blood vessel walls, causing inflammation and clotting that swiftly destroys the kidney. Therefore, a compatible blood type is traditionally required to ensure the recipient lacks antibodies against the donor’s blood group antigens.
Compatibility rules follow those of blood transfusions. A Type O donor is universal because their organ lacks A or B antigens, making it safe for any recipient. A Type AB recipient is the universal recipient because they possess both antigens and lack anti-A or anti-B antibodies. Type O recipients, however, can only safely receive a kidney from a Type O donor, as they have both anti-A and anti-B antibodies.
Beyond Blood Type: Tissue Compatibility and Crossmatching
While ABO matching is the first hurdle, long-term transplant success also depends on Human Leukocyte Antigens (HLA). HLA are proteins on the surface of almost all nucleated cells, serving as genetic markers that allow the immune system to distinguish self from foreign material. The goal is to find a donor whose HLA markers are as close a match as possible to the recipient’s.
HLA typing identifies the specific markers a person inherited. Since a perfect match is rare unless the donor is an identical twin, the focus shifts to ensuring the recipient lacks antibodies that would attack the donor’s specific HLA markers. Anti-HLA antibodies can develop from previous exposure to foreign tissue, such as blood transfusions, prior transplants, or pregnancy.
The crucial test is the crossmatch, a miniature test transplant performed in a laboratory. It mixes the recipient’s blood serum, which contains antibodies, with the donor’s lymphocytes, which express HLA antigens. A “positive crossmatch” means the recipient’s antibodies attack the donor cells, indicating a high risk of immediate rejection. A “negative crossmatch” is necessary to proceed, showing no pre-formed antibodies pose a significant threat to the donor kidney.
Medical Pathways for ABO Incompatible Transplants
Medical science has developed protocols to make ABO-incompatible (ABOi) transplants possible, despite the traditional requirement for compatibility. These procedures, known as desensitization, focus on removing or neutralizing the recipient’s pre-formed anti-A or anti-B antibodies before the transplant. This approach significantly expands the donor pool by allowing a willing living donor to proceed even if their blood type is incompatible.
The primary method for physically removing these antibodies is plasmapheresis, a procedure similar to dialysis. The recipient’s blood circulates through a machine that separates the plasma, which contains the antibodies, from the blood cells. The plasma is discarded and replaced with a substitution fluid, effectively lowering circulating antibody levels to a safe range.
Recipients often receive intravenous immunoglobulin (IVIg) therapy alongside plasmapheresis. IVIg is a preparation of pooled antibodies that suppresses the immune system and prevents the body from rapidly producing new anti-A or anti-B antibodies. This treatment, sometimes combined with immunosuppressive drugs like rituximab, helps maintain the low antibody level achieved by plasmapheresis.
Desensitization protocols require intensive monitoring of antibody levels before and immediately after surgery. The goal is typically to reduce the antibody titer, or concentration, to a specific low threshold, such as 1:8 or less, before the transplant proceeds. ABOi transplants require a more rigorous and sustained course of immunosuppression to ensure the long-term survival of the organ.
Navigating Incompatibility Through Kidney Paired Exchange
For living donor and recipient pairs who are incompatible due to blood type or anti-HLA antibodies, the Kidney Paired Exchange (KPE) program offers a logistical solution. KPE overcomes incompatibility by arranging a “swap” between two or more incompatible pairs. The incompatible donor donates to a compatible stranger instead of their loved one.
In a simple two-way exchange, incompatible Pair A is matched with incompatible Pair B. Donor A gives a kidney to Recipient B, and Donor B simultaneously gives a kidney to Recipient A. This arrangement ensures both recipients receive a compatible organ and both willing donors save a life. Exchanges can also involve complex chains of three or more pairs, sometimes initiated by an altruistic non-directed donor.
KPE programs are facilitated through national registries using computer algorithms to identify the optimal match for each pair. By participating, the donor and recipient pair trade their incompatibility for a compatible match from the database. This solves the blood type or crossmatch problem and often provides the recipient with a better overall HLA match, contributing to longer graft survival.