DDKT – ABO Blood Groups, Tissue Matching, and Sensitization

Deceased donor kidney transplantation (DDKT) is a life-saving option for patients with end-stage renal disease. However, success depends on multiple immunological factors that influence donor-recipient compatibility.

ABO Blood Group And Transplantation

The ABO blood group system is crucial in DDKT, determining donor-recipient compatibility. Kidney transplantation typically requires matching blood types to prevent immediate graft rejection, as naturally occurring anti-A and anti-B antibodies can cause hyperacute rejection if an incompatible kidney is transplanted.

Blood group O recipients face the greatest challenge due to their universal production of anti-A and anti-B antibodies, limiting them to O donors. In contrast, individuals with blood group AB have the broadest compatibility, as they lack these antibodies and can receive kidneys from any ABO group. This disparity leads to longer wait times for group O patients. Data from the United Network for Organ Sharing (UNOS) and the Organ Procurement and Transplantation Network (OPTN) show that blood group O patients often wait significantly longer than AB recipients.

Advancements in ABO-incompatible (ABOi) kidney transplantation have expanded options for patients who would otherwise face prolonged wait times. Desensitization protocols involving plasmapheresis and immunosuppressive therapy can reduce anti-A or anti-B antibody levels, enabling successful ABOi transplants. Studies in The New England Journal of Medicine and Transplantation indicate that with proper preconditioning, ABOi kidney transplants achieve comparable long-term outcomes to ABO-compatible transplants. However, ABOi transplantation remains more complex and resource-intensive, requiring careful monitoring to prevent antibody-mediated rejection.

Sensitization Factors In DDKT

Sensitization in DDKT refers to preformed antibodies in a recipient that can target donor antigens, increasing rejection risk. These antibodies, primarily against human leukocyte antigens (HLA), develop from prior exposure through pregnancy, blood transfusions, or previous transplants. The calculated panel reactive antibody (cPRA) score estimates the percentage of potential donors against whom a recipient has pre-existing antibodies. A high cPRA score makes finding a compatible kidney more difficult, leading to longer wait times and higher rejection risk.

Pregnancy is a major sensitizing event, as the maternal immune system is exposed to paternal HLA antigens from the fetus. Studies in The American Journal of Transplantation show that multiparous women—those with multiple pregnancies—often have higher cPRA scores, complicating their chances of finding a suitable donor. Blood transfusions introduce foreign HLA antigens, contributing to sensitization despite leukoreduction techniques that reduce immunogenicity. Similarly, previous organ transplants can trigger a strong alloimmune response, activating memory B cells and leading to long-term antibody production, further narrowing the donor pool.

Donor-specific antibodies (DSAs) complicate transplantation by increasing the risk of antibody-mediated rejection (AMR). DSAs can activate complement pathways, causing endothelial injury and microvascular inflammation, jeopardizing graft survival. Single-antigen bead assays using Luminex technology precisely identify DSAs, improving compatibility assessments. Research in Transplantation Proceedings shows that even low DSA levels can affect long-term graft outcomes, emphasizing the need for thorough pre-transplant screening and post-transplant monitoring.

Tissue Typing And Crossmatching

Successful DDKT depends on precise tissue matching to ensure donor-recipient compatibility. Tissue typing focuses on HLA, proteins on cell surfaces that help the immune system distinguish self from non-self. Each individual inherits one set of HLA genes from each parent, leading to high variability. Closer HLA matches reduce rejection risk and improve long-term graft survival. Studies from UNOS indicate that recipients with zero HLA mismatches have lower rejection rates and better graft function.

HLA typing uses molecular techniques such as polymerase chain reaction (PCR) and next-generation sequencing (NGS) for high-resolution allele identification, improving precision in matching. While full HLA compatibility is rare, certain loci—particularly HLA-A, HLA-B, and HLA-DR—carry the most weight in transplant success. The Scientific Registry of Transplant Recipients (SRTR) reports that mismatches at these loci affect graft longevity, with HLA-DR mismatches posing the highest rejection risk.

After HLA typing, crossmatching detects pre-existing antibodies that could react with the donor’s HLA. Flow cytometry and complement-dependent cytotoxicity (CDC) assays assess whether a recipient’s serum contains antibodies that could attack donor cells. A positive crossmatch increases the risk of hyperacute or acute rejection, making transplantation unfeasible unless desensitization strategies are used. Flow cytometry crossmatch (FCXM) is more sensitive than CDC, detecting even low levels of DSAs that may contribute to chronic graft dysfunction.