What does a very high Calculated Panel Reactive Antibody (cPRA) percentage indicate about a kidney transplant candidate's sensitization status and transplant probability?

A very high Calculated Panel Reactive Antibody (cPRA) percentage indicates that a kidney transplant candidate has a significant level of sensitization, meaning their immune system has developed pre-formed antibodies against a large proportion of the human leukocyte antigens (HLAs) found in the general donor population. These antibodies are proteins produced by the immune system that recognize and target foreign HLA antigens, which are unique markers present on the surface of most cells in the body, including kidney cells. Sensitization typically occurs due to prior exposure to foreign HLA antigens through events such as blood transfusions, previous organ transplants, or pregnancy. A cPRA of, for example, 99% means that the candidate has antibodies that would likely react positively against 99% of potential deceased or living kidney donors. This positive reaction, detected through a crossmatch test, indicates incompatibility and a high risk of hyperacute rejection if a transplant were to proceed, making that particular donor unsuitable. Therefore, a very high cPRA percentage directly correlates with a severely diminished transplant probability. Such a candidate will face extreme difficulty in finding a compatible donor, as their immune system is poised to reject nearly all available kidneys, necessitating specialized strategies like participation in paired kidney exchange programs, desensitization protocols, or the accumulation of additional wait time points to improve their chances of receiving a compatible organ.