To prevent rejection of donor kidneys, researchers with the PROCARE study are developing a better matching algorithm. In addition, transplant patients with an increased risk of rejection are followed for at least two years. Research leader dr. Henny Otten: "If we find indications for rejection in their blood, we can offer customized medication early."

For most patients with renal failure, a kidney transplant is the best option. In the Netherlands, around 750 kidney patients are on the waiting list for a donor kidney. The waiting time for a donor kidney of a deceased person is on average 2.5 years. Once a kidney patient is eligible for a transplant, it is important that the donor kidney matches the recipient as well as possible. But some of the tests used for this are now 30 years old. As a result, there is not always a good match, which can lead to the rejection of the donor kidney.

"Thanks to funding from the Dutch Kidney Foundation and close collaboration between nephrologists and laboratory specialists, we have been able to map new insights," says medical immunologist Henny Otten (Center for Translational Immunology, UMC Utrecht). The collaboration with all Dutch transplantation centers made PROCARE 1.0 research a special project. “The problem of donor kidney rejection has been investigated from different angles. The insights we have gained with new laboratory techniques are now being applied in all Dutch transplant centers."

Longer functioning

The research team again studied the data of more than six thousand kidney transplants, performed between 1995 and 2005, and investigated what was important for a successful kidney transplant. "We linked the analysis of stored blood samples to data on patient health, such as the period in which a kidney functioned well," says Henny. All data is systematically brought together in a huge database. It is now clear which factors are important and which are not. For example, it appears that the new, sensitive and accurate method for measuring HLA antibodies directed against donors is very important for determining the risk of rejection. Insights such as these help to ensure that donor kidneys can function longer in the future."

Smart match

Kidney patients who are on the waiting list for a transplant depend on dialysis. This replaces only a small part of the kidney function. The quality of life is also limited. In 2019, more than 60 kidney patients died while on the waiting list. More than 100 patients were taken from the list, because they could no longer handle a transplant due to a deteriorated condition. "A more effective allocation of donor kidneys makes patients less likely to return to the waiting list," explains Henny. The expectation is that waiting lists will become shorter in the long term. With a smart match you also minimize the production of HLA antibodies against the donor kidney.

Matching algorithm

The researchers' second project is called PROCARE 2.0. It will start in 2020 and has two pillars. "First we will check the results from our first study on a recent group of patients," says Henny. “We do this to determine which data from PROCARE 1.0 we need to include in order to arrive at a better matching algorithm. To this end, the team will analyze the data from more than 9,000 kidney transplants, performed between 2006 and 2016, using the new insights and analytical techniques from PROCARE 1.0. The aim is to develop a better algorithm for the allocation of donor kidneys.

National collaboration

“In addition, it is important that we can estimate the long-term perspective of each patient as good as possible. The chance of success with a large group of people does not say everything about the individual chances of success," says Henny. To achieve this, the researchers will continue to monitor transplant patients with a high risk of rejection for at least 2 years after the transplant. In these patients, blood is regularly analyzed for the specific types of white blood cells and antibodies. An increase may be an indication of an increased risk of rejection. "If that is the case, then we can provide personalized medication early to prevent this," says Henny. "And because all transplantation centers participate in the project, we can thus achieve a better treatment of the threat of rejection of donor kidneys throughout the Netherlands."

PROCARE is a collaboration between the UMC Utrecht, Amsterdam UMC, LUMC, UMC Groningen, Radboudumc, Maastricht UMC and Sanquin Amsterdam and is funded by the Dutch Kidney Foundation.