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Kidney transplants often fail; this is why

Many kidney transplants fail due to genetic incompatibility.

Washington: Genetic incompatibility may be the reason why many kidney transplants fail, even if donors and recipients fit well together, a recent study has observed.

According to the study published in the Journal of Medicine, genomic collision is a genetic incompatibility between the kidney donor and the recipient, causing the recipient to build up an immune attack on the donor protein.

The new study could lead to more precise matching between donors and patients and kidney failure. The same genomic collision may also occur with heart, liver and lung transplants.

Successful organ transplantation depends on ensuring genetic compatibility between the donor and the recipient. This is done by matching the human cell surface proteins of the donor and recipient to help the immune system determine which cells are as foreign as possible.

However, mismatches can only explain about two-thirds of transplants that fail for immunological reasons. "The rest of those errors are probably due to less common antigens, or so-called less important histocompatibility antigens, but the identity of most of these antigens and how they lead to rejection is largely unknown," said senior co-author Krzysztof Kiryluk.

The study found that kidney recipients with two copies of a deletion near a gene called LIMS1 had a significantly higher risk of rejection when the donor's kidney had at least one full-size version of the same gene. Transplanted organs usually experience a significant period of low oxygenation, which appears to enhance the genomic collision.

The findings may apply to other types of organ transplants, because LIMS1 is also expressed in the lungs, heart and liver. Similarly, other genetic incompatibilities can also contribute to the rejection of these organs.

"This project illustrates how genetic analysis makes clinical care possible by enabling better matching and the antibody test may offer a non-invasive method for screening for organ rejection in persons with an existing transplant," explained another co-author Ali G. Gharavi from.

"The LIMS1 gene has not been previously discovered in previous searches, partly due to the limited sample size of previous studies. We estimate that a traditional genome-wide association study would need to analyze a minimum of 13,000 kidney recipients to find this gene," Kiryluk concluded.

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