A laboratory test that measures the strength of a specific immune response, namely trained immunity, one week after transplantation predicts how long a donor kidney will last. This is evident from a ten-year research study by Radboudumc on 96 patients. Because patients do not currently receive medication against this trained immunity, this research offers leads to improve the lifespan of donor kidneys. The study has been published in the American Journal of Transplantation.
Kidney transplant outcomes have improved dramatically in recent decades. In the 1990s, about 40 percent of transplanted kidneys experienced a rejection response within the first year. This percentage has now dropped to ten to fifteen percent. In addition, doctors today can almost always save the kidney in the event of a rejection reaction. This progress is mainly due to drugs that suppress the body’s acquired immune response.
Memory
However, while rejection has decreased tremendously in the first year, the long-term life span of transplanted kidneys has barely improved: a donor kidney lasts about 15 to 20 years on average. According to internist-nephrologist Raphaël Duivenvoorden of the Radboudumc, in the long term, more attention needs to be paid to a body response other than the acquired immune system, namely the innate immune system.
“Patients now receive only drugs that target T cells and thus suppress the acquired defense. That body response is slow, specific, has a strong memory, and has always received much attention in organ transplant research,” Duivenvoorden says. “But for about a decade, we’ve known that another form of immunity, innate immunity, which responds more quickly and less specifically, also has a memory. We call that trained immunity. And that very response predicts how long a kidney will ultimately last.”
Tolerance
Duivenvoorden and his team followed 96 recipients of a donor’s kidney for up to ten years after surgery. In doing so, they looked at how long the kidney continued to function. They also took measurements of blood samples from the patients before and after surgery. Promovenda Inge Jonkman: “We used a laboratory test, which shows to what extent the blood stimulates the trained immunity. What turned out: the lower the reaction in the test to the blood one week after surgery, the longer the transplanted kidney lasts.”
This finding provides clues to extending the lifespan of a donor kidney. Duivenvoorden: “We think the immune system can become more tolerant of the graft if we inhibit trained immunity. This could lead to less rapid scarring of the kidneys, which we want to investigate further. Now that we know that innate immunity plays a greater role in the longevity of transplanted kidneys than thought, we can develop new treatment strategies. By creating a treatment that inhibits trained immunity, we may be able to ensure that transplanted kidneys last longer.”
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