Targeting miR-21 to inhibit the inflammatory response following ischaemic kidney injury

Around 5000 people in the UK are waiting for a kidney transplant as the optimum treatment in kidney failure. To meet this demand there is a push to use organs from more marginal donors.

These organs are more susceptible to injury from ischaemia reperfusion so by targeting this injury we could improve the quality and availability of donor organs, leading to better outcomes for patients.

I will investigate how ischaemia reperfusion injury in the kidney is affected by an inhibitor to microRNA-21 using a human whole organ model. I’ve chosen to target microRNA-21 as inhibition is protective in rodent models of kidney injury.

An inhibitor has also reached clinical trials in Alport Syndrome raising the possibility of progressing to early trials in transplantation.

I will deliver a microRNA-21 inhibitor during machine perfusion to human kidneys that have been declined for transplantation.

I will explore the effect on gene expression and assess the impact on kidney injury through urine output, histology and biomarker measurements.

My project brings together the technology of machine perfusion to deliver a microRNA inhibitor directly to donor kidneys in isolation. If this strategy reduces kidney injury, we could potentially improve early transplant outcomes and graft longevity.