Gene signatures help kidney transplant success

Scientists have discovered a molecular signature for the allostatic load ­– or ‘wear and tear’ – of kidneys which could help clinicians understand why some kidney transplants don’t work as well as expected.

The University of Glasgow-led research, published in Aging Cell explains why allostatic load develops at a molecular and cellular level, how it affects physiological function and the role of age-related organ capability and resilience.

Paul Shiels, Professor of Geroscience at the University’s Institute of Cancer Sciences, said: “We now have strong evidence that an organ’s biological age, in combination with physiological stress, plays a major role in DGF, or impaired function, occurring. The findings also suggest that these effects are driven by donor characteristics, which may be more of a factor than transplant stress itself.

“Our findings are important because, not only have we identified the reason why some kidney transplants don’t work when transplanted, we also demonstrate that miles on the biological clock affect the physiological function of organs. This isn’t just clinically important, but is also relevant to how we age and how we can maintain good health in old age.”

In the study, the scientists, in collaboration with NHS Great Glasgow & Clyde surgeons and pharmaceutical company GlaxoSmithKline, studied transplanted kidneys which developed Delayed Graft Function, or DGF. The kidneys which displayed DGF appear to be predisposed to exhibit a greater response to transplant stress and take longer to resolve this.

Previously, the scientists demonstrated that the biological age of transplanted kidneys was important for how well a kidney worked following transplantation, but it was not known why DGF, and the resulting impaired kidney function, occurred.

The scientists now demonstrate that at a molecular level, the kidneys studied displayed a greater magnitude of change in key genes, and elevated expression of features of ageing, consistent with increased allostatic load, or wear and tear.

Prof Shiels added: “By using the signature set of genes from this study to identify less resilient organs before they meet a new recipient immune system, transplant stress could be reduced and outcomes improved. Significantly, the study has identified the targets for doing so, which may be applied not only for transplantation, but for other organs as we age, with a view to improving our years of healthy living.”