Study identifies why the human body rejects a pig kidney transplant

For the first time, researchers have evaluated the rejection of a pig kidney in a human body for two months from the day of transplantation. The study identified the main mechanisms of the human immune system against the pig organ, insights useful for the development of therapies to prevent rejection.

Valentin Goutaudier, a nephrologist doing postdoctoral research at the Paris Institute for Transplantation and Organ Regeneration in collaboration with the Langone Transplant Institute at New York University, was one of the researchers responsible for the study. The researcher's career is intertwined with the goal of understanding how the human body rejects organ transplants and, from there, developing therapies that prevent this rejection process.

The image shows a surgical team of three healthcare professionals, all dressed in blue surgical gowns and masks. They are focused on a surgical procedure, focusing on a central area where they are using surgical instruments. The setting is an operating room, with medical equipment visible in the background, including monitors and fluid bags. — Medical staff at Massachusetts General Hospital in Boston, USA, where a pig kidney transplant was performed on a living patient - Michelle Rose - 16.Mar.24/Massachusetts General Hospital/AFP

This is the case with the new research on pig kidneys. Doctors have already performed pig kidney and heart transplants on humans , but rejection is a challenge. Goutaudier had previously investigated the immune system's negative response to xenotransplantation, a procedure involving organ transplants between different species, but only for a short period after surgery.

In the new study, presented at a scientific conference of the European Society for Organ Transplantation (ESOT), the analysis time was longer. "We were allowed to continue the study for up to two months after the transplant. This allowed us to evaluate the long-term human response," says Goutandier.

The research consisted of analyzing samples from the kidney of a pig transplanted into a human at seven different time points during the two-month study. Scientists observed that, by the tenth day after the transplant, human antibodies were already identified in the pig organ. This response peaked approximately one month after surgery.

Pig kidney successfully transplanted into human patient

In addition to examining the samples, the investigation was innovative in adopting spatial transcriptomics. The method allowed the identification of specific regions of the kidney where rejection occurred and the main cells involved in the immune response to the transplant.

In the first case, researchers observed that rejection was predominant in the glomeruli, the kidney units responsible for blood filtration . This conclusion was novel and differs from that of human organ transplants. Goutandier explains that, in human-to-human transplants, rejection spreads to other areas of the kidneys.

The step-by-step process of organ harvesting

Regarding immune responses, the study found that innate immune antibodies, such as macrophages, were predominant in the rejection of the swine kidney. "Innate immunity is ancestral immunity. It's shared by different species. So it makes sense that these ancient innate immune cells recognize different species," explains Goutandier. Other immune system cells, such as B and T lymphocytes , were also identified in the organ rejection, but to a lesser extent.

This immune response pattern is similar to what researchers have observed when transplanting pig hearts into humans . Meanwhile, transplanting pig livers into people may produce a different response, but there are also publications reporting some similarities with the rejection observed in kidney transplants.

By identifying in more detail how pig kidney rejection occurs, the study opens the door to developing therapies that prevent the negative response to transplantation. In the research, an experimental, personalized treatment was tested, with positive results in stopping organ rejection.

The idea for the future is to understand all the data compiled by the study to propose therapies for this type of transplant. "Now we have a better understanding of the [pig kidney] rejection process. The next step is to provide precise therapy," says Goutandier.

The researcher points out that it's possible to repurpose existing drugs for this purpose, which would reduce the costs and time required to develop a therapy from scratch. However, it's necessary to precisely identify these therapeutic targets to determine which treatments will be effective for xenograft rejection.