Organ ‘bio-age’ determines performance of transplanted kidneys

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Organ ‘bio-age’ determines performance of transplanted kidneys, scientists discover

Issued: Fri, 23 Jan 2009 16:07:00 GMT

Scientists at the University of Glasgow have discovered that the bio-age of a kidney is the biggest factor in predicting how well it might work and how long it might last after transplantation and potential problems that might arise.

They can now tell, for example, why some older organs can work very well, while some younger organs don’t.

The researchers developed a method of measuring bio-age by examining a number of substances – or biomarkers – within kidneys to ascertain how healthy their cells were by looking at how many miles were on the cells’ clock, as opposed to simply how chronologically old they were.

They found that bio-age was twice as influential as chronological age in determining the future function of transplanted kidneys, but by combining the two factors doctors can make the best choice of which organs are most suitable for transplant.

The discovery could potentially be applied to other organs and have major implications for the NHS, saving money and wastage, improving patient care and combating donor shortages by making the most of the limited pool of organs available for transplantation.

Dr Paul Shiels, Senior Lecturer in the Department of Surgery, Division of Cancer Sciences, University of Glasgow, said: “The age of any organ is determined not by its age in years but by how many miles are on its cellular clock, ie: how biologically young and healthy its cells are and how much capacity they have for repairing themselves.

“The more damage cells accumulate the less they are able to repair themselves, but damage can be accumulated over different periods of time. So, older people who have been exposed to fewer stressors in life may have younger organs than younger people whose cells have greater damage.

“Through our study we have been able to determine the bio-age of kidneys and predict how long they are likely to last and what sort of reactions or complications might occur after transplantation, which enables us to prescribe medicine to combat those effects before they exhibit themselves.

“Further larger trials are needed but ultimately this could make more organs available for transplant and improve the quality of life of donor recipients.

“We believe this technique could be applied to a range of other organs and to study conditions such as cancer and neurodegeneration.”

Donor age is currently the main determiner of which kidneys will be used for renal transplant as older organs often perform poorly, though many function just as well as younger ones.

However, the new research enables doctors to find out through a simple blood test, whether kidneys from older people are actually biologically younger than their years and suitable for transplant.

Kidney function can be determined by measuring blood levels of creatinine. Creatinine is a waste product in the blood created by the normal breakdown of muscle cells during activity. Healthy kidneys take creatinine out of the blood and put it into the urine to leave the body. It is the kidneys’ job to filter creatinine so if they are not working properly, creatinine levels in the blood will be elevated.

The researchers found that kidneys which had lower levels of the gene cyclin-dependent kinase 2a (CDKN2a) pre transplant, had lower levels of creatinine after six months and one year post transplant, and hence were functioning better.

The research, which involved Surgeons at Glasgow’s Western Infirmary and looked at around 75 organs, was funded Darlinda’s Charity for Renal Research and the Cunningham Trust.

The scientists are now in the process of applying for more funding to extend the trial to look at larger numbers of organs and difference types of genes.

Notes to editors

    * Darlinda’s Charity was established in 1987 by Sunday Mail astrologer Rita Madhok, better known as Darlinda to readers, after she was treated for renal failure at the Western Infirmary. She wanted to give something back to the medics who had helped her and established Darlinda’s. After passing away in 1995, Rita’s husband, Dr Rajan Madhok continued the work of the charity which is the largest benefactor of the Western Infirmary’s Renal Unit. Darlinda’s has raised £700,000 since 1987. www.darlindascharity.co.uk
    * The Cunningham Trust is a Scottish based Trust funding basic biomedical research.
    * The gene CDKN2a is believed to help keep cells in a state of senescence – or old age – when they can no longer divide. Therefore the less CDKN2a there is in an organ, the younger the organ is biologically. Most cells are limited in the number of times they can divide, due to the risk of genetic errors occurring over time. Often, cells can malfunction and continue to divide, essentially becoming immortal, and result in cancers.

For more information contact Stuart Forsyth in the University of Glasgow Media Relations Office on 0141 330 4831 or email s.forsyth@admin.gla.ac.uk

http://www.gla.ac.uk/news/headline_106927_en.html