(Vienna, 6 August 2026) In a study recently published in eBioMedicine, a research team from the Division of Nephrology of the Department of Medicine III has confirmed that, in addition to HLA tissue compatibility, genome-wide genetic compatibility also significantly influences the long-term success of kidney transplants. Furthermore, a combined compatibility score has been developed which could help to better predict the individual risk of rejection and tailor immunosuppressive therapy more precisely.
Kidney transplantation is the best treatment for patients with irreversible kidney failure. It not only prolongs life but also usually enables those affected to enjoy a near-normal quality of life. A prerequisite for long-term transplant success is that the immune system accepts the donor organ as well as possible. To date, the selection of a suitable donor organ has been based primarily on so-called HLA tissue markers. These molecules are found on almost all cells in the body and are used by the immune system to distinguish between "self" and "non-self ". The better these tissue markers match between donor and recipient, the lower the risk of an immunological reaction (rejection). However, HLA genes account for only around 0.1 per cent of all human protein-coding genes. Whether genetic matching in the rest of the genome also plays a role has, until now, been insufficiently investigated.
As early as 2019, the research group was able to demonstrate for the first time in a study published in The Lancet (DOI: 10.1016/S0140-6736(18)32473-5) that genome-wide genetic compatibility between donor and recipient has a significant influence on the long-term survival of kidney transplants. In the study now published, state-of-the-art exome sequencing technologies and a specially developed bioinformatics pipeline were utilised. This enabled the influence of genome-wide genetic compatibility, in addition to traditional HLA matching, to be investigated in an independent cohort.
The key finding: the earlier findings were impressively confirmed. The influence of genome-wide genetic compatibility on graft survival was almost identical to that reported in the 2019 study. Furthermore, the researchers developed a new combined compatibility score that takes into account both HLA and genome-wide genetic matching.
"This combined score could represent an important step towards personalised transplant medicine in the future," says study leader Rainer Oberbauer, Head of the Division of Nephrology and Dialysis at the Department of Medicine III at MedUni Vienna. "This could protect low-risk patients from overtreatment whilst enabling more targeted treatment for high-risk individuals – with the aim of further extending the lifespan of transplanted kidneys and reducing the side effects of therapy." The study was funded by a grant from the Vienna Science and Technology Fund and the NIH/NIAID.
Publication: eBioMedicine
The combined impact of HLA and non-HLA mismatch between donors and recipients on kidney transplant survival: a genomic analysis in a prospective cohort.
Michael Kammer, Andreas Heinzel, Stephen Shoebridge, Roman Reindl-Schwaighofer, Karin Hu, Hao Shan Chen, Alexander Kainz,Ismail Daoudi, Ana F. David, Gottfried Fischer, Brendan Keating, Matthias Niemann, Rainer Oberbauer.
https://www.sciencedirect.com/science/article/pii/S235239642600304X