Analyzing donor-recipient mismatches in kidney transplants

Kidney transplant survival and the genetic landscape of donor-recipient variations.

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Kidney transplantation is a life-saving medical procedure that offers a chance for a better quality of life for individuals with end-stage kidney disease. However, the success of kidney transplantation depends on various factors, one of which is the compatibility between the donor’s kidney and the recipient’s body. Incompatibilities or mismatches between the donor and recipient can lead to complications and reduce the chances of a successful transplant. This new study from Yale University delves into the importance of studying these mismatches in kidney transplantation.

Throughout evolution, humans and all mammals have developed the ability to distinguish between their cells and foreign ones. This crucial insight comes from Madhav Menon, MD, an associate professor of nephrology medicine and the study’s corresponding author.

Madhav Menon said, “This is great for fighting infection but also causes the body to mount an immune response and reject a transplanted kidney that it recognizes as foreign. The best scenario for successful transplantation is receiving an organ from an identical twin. Suppose the donor is a non-identical twin or a sibling. In that case, the kidney will still be rejected because the body recognizes even the smallest differences.”

Researchers have found that a specific region in our genes called the human leukocyte antigen (HLA), located on chromosome six, is essential for kidney transplant success. If the HLA genes of the donor and recipient are similar, the transplant is more likely to succeed.

Researchers like Madhav Menon, MD, are trying to understand another gene called LIMS1. Learning more about how it affects transplants could help create treatments for cases where donor and recipient genes differ.

Even when HLA genes match, transplants can still fail, so Menon is investigating if other genes in our genes need to be checked for the transplant to work well.

In their research, Menon and his team examined 20,000 genes in the human genome, not including HLA genes. They looked at around 600 kidney transplants and found that a mismatch in a gene called LIMS1 increased the risk of the transplanted kidney failing.

LIMS1 gene mutations, joint in the U.S., can lead to changes in another nearby gene called GCC2 and its protein levels. When there’s a mismatch in LIMS1, it can cause scarring in the transplanted kidney and immune reactions in the recipient.

This study, published in the Journal of Clinical Investigation, is essential for the transplant community. According to Menon, It can help identify risk levels, monitor transplant patients, and possibly develop new treatments.

“If we can figure out how this LIMS1 mismatch works, we can create treatments for cases where donor and recipient genes are different,” said Dr. Menon.

Yale’s Nephrology Section is dedicated to providing top-notch patient care, conducting research, and educating future leaders in nephrology. They aim for their faculty and trainees to become leaders in academic nephrology. More about their mission and work is given on their website, Nephrology.

In conclusion, the study of mismatches between donor and recipient in kidney transplantation is a critical area of research that holds promise for enhancing the success rates of kidney transplants. By understanding genetic variations and their impact on transplant outcomes, medical professionals can develop more precise and practical strategies to ensure the long-term survival of transplanted kidneys and the well-being of transplant recipients.

Journal Reference:

  1. Zeguo Sun, Peter S. Heeger et al., Multiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival. The Journal of Clinical InvestigationF. DOI: 10.1172/JCI170420.
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