Who are highly sensitized kidney patients?
Among the thousands of individuals in need of a kidney transplant worldwide, there is a consistent group for whom the search for a suitable donor presents a unique set of challenges. These patients are called highly sensitized.
Highly sensitized patients have very high levels of antibodies which react to foreign tissues. These antibodies are called donor specific antibodies (DSAs) and are typically generated due to previous blood transplants, pregnancy as well as previous transplants. A consequence of high DSA levels is that these patients have a much lower chance to find an acceptable matched donor. Therefore, the patients accumulate on transplant waiting lists facing a much longer time on dialysis and for some, never able to receive a matched donor kidney.
There are over 70,000 patients on kidney transplant waiting lists in the European Union (EU) and United Kingdom (UK) alone, with approximately 20,000 new patients added to the kidney transplant waiting list each year1. Of these, between 10 and 15% are classified as highly sensitized2. In some countries highly sensitized patients make up as much as 30% of the waiting list2.
What leads to a patient becoming highly sensitized?
The process leading to the creation of DSAs is called sensitization and occurs when a patient has been exposed to foreign human proteins, meaning not created in their own body, for example due to a previous organ transplant, a blood transfusion or pregnancy.
The severity of the sensitization is defined by three factors: the broadness of the sensitization (meaning the number of human leukocyte antigens, HLAs, for which a patient has developed unacceptable DSAs), the strength of the antibody reaction, and the specificities. The higher these factors, the lower the likelihood of finding a compatible donor organ. For example, patients who are highly sensitized (cPRA≥80%) have antibodies against numerous common HLAs that result in ineligibility to >80% of the organs3.
The barriers to successful transplant
When kidney patients experience the loss of kidney function, called End Stage Renal Disease (ESRD), it becomes necessary to make up for the lost kidney function through a renal replacement therapy (RRT), which involves either dialysis or kidney transplantation.
When transplanting a patient, the ideal solution is to use a HLA compatible organ, as the risk of rejection increases with the level of incompatibility between the donor and the recipient.
When a compatible organ is not available, an incompatible organ can be considered as a potential alternative. Without effective therapies when transplanting an incompatible organ, the immune system can trigger an immune response against a transplanted organ, which can potentially lead to the loss of the organ in a short period of time.
A much longer wait on dialysis
The presence of DSAs remains a significant and often impenetrable barrier to kidney transplantation for highly sensitized patients.This results in some patients living on dialysis for years, with four to six hours of treatment three to four times per week, which is associated with high cost, a poor quality of life and an increased mortality rate4.
1. Newsletter Transplant 2015-2021. Available at: https://freepub.edqm.eu/publications. Last accessed November 2021.
2. EDQM. (2020). International figures on donation and Transplantation 2019 and SRTR Database and individual assessments of allocation systems.
3. Melissa Y Yeung, “Overview of HLA sensitization and crossmatching” Available at: https://www.uptodate.com . Last accessed November 2021.
4. Orandi et al., “Survival Benefit with KidneyTransplants from HLA-Incompatible Live Donors”, N Engl J Med (2016;374:940-50) Data from Global Observatory on Donation and Transplantation, http://www.transplant-observatory.org.