The donor dilemma

Having a kidney transplant is the best treatment for kidney failure but there is a drastic shortage of suitable organs. More than 5,000 people are on the kidney transplant waiting list and five people die every week waiting for their new kidney.  

To save more lives, doctors are now starting to accept ‘marginal’ kidneys– kidneys that may not be in an ideal condition, often from older or higher risk donors– but these may work less well after transplantation and patients may then require another transplant.   

Rescuing marginal kidneys

Normothermic perfusion is a technique pioneered with our funding by Professor Mike Nicholson, which revives donor kidneys by flushing them with warm oxygenated blood prior to transplant. This offers an excellent opportunity to give special treatments directly to the kidney before transplantation and as it is performed while the kidney is outside of the body, there are fewer concerns about side effects in a patient.  

Dr Emily Thompson and her team are investigating therapies that can be delivered via normothermic perfusion to revive and repair these marginal kidneys. Emily has previously shown that treating kidneys with stem cells helps to repair damage and improve their function and this newly published work explores the possibility of using a novel drug that interferes with damaging molecules in the kidney. 

MicroRNAs can cause damage to donor kidneys and are an attractive target for therapy

Ribonucleic acid (RNA) is an important molecule that converts genetic information from our DNA into the body’s proteins. MicroRNAs are very small strands of RNA that can bind to larger RNA molecules and stop them from making proteins. Researchers have seen changes in the levels of microRNAs in a range of different diseases, including cancer, autoimmune and degenerative diseases and they have also been shown to play a role in ischaemia-reperfusion injury – the damage that happens when blood flow returns to a tissue that has been starved of oxygen for a period of time, as is the case during kidney transplant. 

Targeting microRNAs to rescue damaged donor kidneys

It is possible to make a drug that targets microRNAs and stops them from working but there is a big hurdle to overcome in making sure the drug reaches the right place without causing too many side effects.  

In this study, Emily used the normothermic perfusion technique to deliver a drug that targeted one specific microRNA that is believed to be involved in ischaemia-reperfusion injury to human kidneys that had been deemed unsuitable for human transplant.  

The team showed that the drug was delivered directly to the damaged cells, and it restored the levels of the target proteins to normal levels. This is huge step forward in the treatment of damaged kidneys as it means other drugs could be designed and delivered in a similar manner to block the activation of certain genes associated with kidney injury.  

Emily said: “This is really exciting as it offers a new way to make more kidneys suitable for transplant. It could offer hope to more people on dialysis and potentially shorten the waiting list.  This work has completely changed our thinking as it shows that we can pre-treat the kidney directly, instead of treating the whole patient before or after transplantation. This opens up exciting opportunities to explore other therapies in this setting, for example, treatments that could potentially reduce the need for lifelong immunosuppression. Currently these tests are done in the lab but if they transfer to the patient setting, as we hope they will, those who receive a transplant may receive better quality kidneys that last a lifetime.” 

This work was awarded The Patey Prize at The Surgical Research Society Annual Congress in 2021. The Patey Prize is widely regarded as the highest award for surgical research in the UK.