Laboratory test after surgery predicts donor kidney longevity Underexplored Immune Mechanism Plays Crucial Role in Transplantation

A laboratory test that measures the strength of a specific immune response, known as trained immunity, one week after transplantation can predict how long a donor kidney will last. This is shown by Radboud university medical center based on a study following 96 patients for ten years. Since patients currently do not receive medication against this trained immunity, this research provides new insights that could help improve the longevity of donor kidneys.

The outcomes of kidney transplants have improved significantly over the past decades. In the 1990s, approximately forty percent of transplanted kidneys experienced a rejection reaction within the first year. This percentage has now decreased to ten to fifteen percent. Moreover, nowadays, doctors can almost always save the kidney even if a rejection occurs. This progress is mainly due to medications that suppress the body's acquired immune response.

Memory

While rejection in the first year after transplantation has greatly diminished in the past decades, the long-term survival of transplanted kidneys has barely improved: a donor kidney typically lasts around fifteen to twenty years. According to internist-nephrologist Raphaël Duivenvoorden of Radboudumc, more attention should be given to another immunologic response for long-term survival, namely innate immunity.

‘Patients currently only receive medication targeting T-cells, which suppresses the acquired immune response. This immunologic reaction is slow, specific, and has a strong memory, which has always been the focus of organ transplant research’, says Duivenvoorden. ‘But for about ten years now, we’ve known that another form of immunity, the innate immunity, which reacts 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 transplanted kidney will ultimately function.’

Tolerance

Duivenvoorden and his team followed 96 recipients of donor kidneys for up to ten years after surgery. They observed how long the kidney continued to function and also measured blood samples from the patients before and after the operation. PhD candidate Inge Jonkman explains: ‘We used a laboratory test that shows to what extent the blood stimulates trained immunity. What did we find? The lower the reaction in the test on blood from one week after the surgery, the longer the transplanted kidney lasted.’

This finding offers new possibilities to extend the lifespan of a donor kidney. Duivenvoorden: ‘We believe that the immune system could become more tolerant to the transplant if we inhibit trained immunity. This could potentially lead to less rapid scarring of the kidneys, which we plan to investigate further. Now that we know that innate immunity plays a larger role in the longevity of transplanted kidneys than previously thought, we can develop new treatment strategies. By creating a treatment that inhibits trained immunity, we might be able to extend the lifespan of transplanted kidneys.’

About the publication

This research has been published in the American Journal of Transplantation: Trained immunity suppression determines kidney allograft survival. Inge Jonkman, Maaike M.E. Jacobs, Yutaka Negishi, Cansu Yanginlar, Joost H.A. Martens, Marijke Baltissen, Michiel Vermeulen, Martijn W.F. van den Hoogen, Marije Baas, Johan van der Vlag, Zahi A. Fayad, Abraham J.P. Teunissen, Joren C. Madsen, Jordi Ochando, Leo A.B. Joosten, Mihai G. Netea, Willem J.M. Mulder, Musa M. Mhlanga, Luuk B. Hilbrands, Nils Rother, Raphaël Duivenvoorden. DOI: 10.1016/j.ajt.2024.08.006.

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