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 shown by ten years of research from Radboudumc involving 96 patients. Since patients currently do not receive medication against this trained immunity, this research offers clues to improve the lifespan of donor kidneys. The research has been published in the American Journal of Transplantation.
The results of kidney transplants have improved significantly over the past few decades. In the 1990s, about forty percent of transplanted kidneys experienced a rejection reaction within the first year. This percentage has now decreased to ten to fifteen percent. Additionally, doctors today can almost always save the kidney in case of a rejection reaction. This progress is mainly due to medications that suppress the body’s acquired immune response.
Memory
However, while rejection in the first year has drastically decreased, the lifespan of transplanted kidneys in the long term has barely improved: a donor kidney lasts on average about fifteen to twenty years. According to internist-nephrologist Raphaël Duivenvoorden from Radboudumc, more attention should be paid to another bodily response for that long term, namely the innate immunity.
“Patients currently only receive medications targeting T-cells, thus suppressing the acquired immunity. That immune response is slow, specific, and has a strong memory, and has always received much attention in transplant research,” says Duivenvoorden. “But for about ten years, we have known that another form of immunity, innate immunity, which responds faster and less specifically, also has a memory. We call this trained immunity. And it turns out that this response is a predictor of how long a kidney ultimately lasts.”
Tolerance
Duivenvoorden and his team followed 96 recipients of a donor kidney for up to ten years post-surgery. They investigated how long the kidney continued to function. They also took measurements from blood samples of the patients before and after the surgery. PhD candidate Inge Jonkman: “We used a laboratory test that shows to what extent the blood stimulates the trained immunity. What did we find? The lower the response in the test of the blood taken one week after the operation, the longer the transplanted kidney lasts.”
This finding provides insights into prolonging the lifespan of a donor kidney. Duivenvoorden: “We believe that the immune system may become more tolerant of the transplant if we suppress trained immunity. This may lead to reduced scarring of the kidneys, which we want to investigate further. Now that we know that innate immunity plays a greater role in the lifespan of transplanted kidneys than previously thought, we can develop new treatment strategies. By creating a treatment that suppresses trained immunity, we may ensure that transplanted kidneys last longer.”
Emerging Trends in Kidney Transplantation Insights
Recent research from Radboudumc reveals exciting breakthroughs in improving the longevity of transplanted kidneys. A lab test measuring trained immunity—a particular immune response—one week post-transplant could serve as a predictor for how long a donor kidney will last. With no current medications targeting this aspect of immunity, the findings open up new avenues for enhancing kidney transplant outcomes.
Understanding Immunity in Transplantation
Traditionally, medical advancements focused on suppressing acquired immunity, predominantly the T-cell response, reducing early rejection rates from 40% in the 1990s to a promising 10-15% today. However, while short-term outcomes have drastically improved, the average lifespan of a transplanted kidney remains stuck at 15-20 years. Researchers now emphasize the need to explore innate immunity, specifically trained immunity, which has shown potential as a significant factor influencing long-term kidney transplant viability.
Trained Immunity as a Predictor
Dr. Raphaël Duivenvoorden and his team studied 96 kidney transplant recipients over a decade, linking post-operative blood response to longer kidney function. The critical discovery was that a lower response in trained immunity correlated with extended kidney lifespan. This insight reshapes our understanding of how the body’s immune system can adapt and tolerate transplant organs.
Paving the Way for New Treatments
Future treatment strategies may focus on moderating trained immunity to enhance organ tolerance, potentially reducing kidney scarring over time. By inhibiting the effects of trained immunity, transplantation procedures could evolve, promoting donor kidney longevity. As research progresses, tailored therapies that modulate innate immune responses could revolutionize kidney transplantation and patient outcomes.
Looking Ahead
The shift in focus from solely acquired to the nuanced role of trained immunity redefines the future landscape of organ transplantation. As researchers dive deeper into this promising area, we may witness a significant transformation in how kidney transplants are approached, aiming for longer-lasting and healthier outcomes for patients.