Targeting the immune response to improve outcomes after kidney transplant

27 March 2025

Dr Louise Walport from Imperial College London has received a Kidney Research UK research project grant of £250,000 to look at developing a drug to prevent the kidneys being damaged by the immune system during transplant surgery. This will be a collaborative project with Dr Ben Schumann from Imperial College London and Professor Steven Sacks and Dr Subhankar Mukhopadhyay from King’s College London. This project builds on findings from previous Kidney Research UK funded research by members of this group.

The problem

Over 6,000 people in the UK are on the waiting list for a kidney transplant. Maximising the number of kidneys available for transplant and ensuring good long-term health of transplanted kidneys is crucial to ensure that as many people as possible can receive a donor kidney.

Decreased blood flow to a donor kidney activates the immune system in the recipient, which can damage and reduce the lifespan of the kidney and can make some unsuitable for transplant. Poor circulation in the donor, and problems during the surgical retrieval process, can both reduce blood flow to a donor kidney.

The solution

Certain markers are found on the surface of kidney cells in response to decreased blood flow, and they are recognised by a protein which activates the first part of the immune response, damaging the marked cells. Louise will look at developing drug molecules which prevent the interaction between this protein and the marker molecules made by the kidney cells when blood flow is lost.

Drug development: a closer look

The surface of the protein being targeted is shallow, so finding a drug that is able to bind to it and have its effect is more challenging.

Cyclic peptides (special types of small protein molecule containing a ring structure) are able to form interactions and bind to these shallower surfaces. Cyclic peptides which bind to the protein target will be selected from a large collection of molecules and coated with markers similar to those which the protein usually binds.

These cyclic peptides will be tested to see if they can prevent the inflammatory response to loss of blood flow in the kidney.

A green image, which looks like lots of peas squashed together, with grey lines with red and blue dots on them

Image of a cyclic peptide (grey) bound to a protein (green), created by Louise’s lab using a technique called cryo-electron microscopy which allows researchers to “see” what proteins look like (Image from the RCSB PDB (RCSB.org) of PDB ID 8R8U).

What could this mean for kidney patients?

By developing a drug which prevents inflammation following loss of blood flow before and during transplant surgery, this could inform treatments that increase the number of kidneys suitable for transplant in the future.

Head and shoulders of a female wearing a striped top.

Dr Louise Walport

Meet the researcher

“I am passionate about leveraging the potential of cyclic peptide drugs to improve patients’ lives. By combining mine and Ben’s expertise in chemistry, with Steve’s and Subhankar’s expertise in kidney biology, we hope our work will lead to a new approach to increase the numbers of healthy kidneys available for transplantation. I am excited to get started and grateful to Kidney Research UK and all its donors for this opportunity.” Dr Louise Walport