Research

In this section of the Charity’s website medical researchers that have received Grants from Kidney Research Yorkshire have an opportunity to describe progress on the work in which they are engaged.

Making Research Happen

Here at Kidney Research Yorkshire we have just one thing that we focus on every day. This is to ensure that the highest quality research is funded, and that this makes a real difference to people’s lives.

Dr Andrew Mooney (scientific adviser to Kidney Research Yorkshire) and Dr Nick Hornigold (post-doctoral scientist supported by Kidney Research Yorkshire) attended the American Society of Nephrology Annual Meeting in Denver, Colorado.

Their work, which has been supported by Kidney Research Yorkshire , had been selected for presentation at their annual meeting meeting, which is widely regarded to be the most important kidney research meeting in the world.

Dr Hornigold presented three pieces of work at the meeting. The research he conducts with Kidney Research Yorkshire support focuses on the role of a protein, Hic-5, which appears to play a critical role in the development of kidney disease. Hic-5 has previously been identified as an important protein in moths, where it plays a role in the development of muscles used for flying, but amazingly it is found in many other animals where it has been proposed to control several different processes important for life.

Dr Hornigold has shown that it is not normally present in the glomerular part of kidneys, where blood filtering happens, but it is present in some of the tubules in the kidneys, where the filtrate from the blood is processed into urine. Dr Hornigold’s research shows that as kidney disease develops, Hic-5 appears in glomerular cells in the kidney, and its appearance is associated with a change in these cells so that they behave differently and start to form a scar in kidneys that stops them working properly. This work was published earlier this year in the premier renal journal Kidney International.

At the meeting, Dr Hornigold presented the most recent advances in this work, supported by Kidney Research Yorkshire. His first presentation demonstrated that with experimental drugs it is possible to prevent the appearance of Hic-5 in experimental kidney disease in animals, and this is associated with an improved outcome. His second presentation explained how this effect happens, and his final presentation explained the recent fascinating observation that during kidney disease, Hic-5 disappears from the tubular cells that normally have this protein inside them. Therefore it appears that Hic-5 has important roles to play in different types of kidney disease.

Dr Hornigold said “Attending a meeting like the American Society of Nephrology is a great opportunity. We have the chance to show what we have been doing in Yorkshire to a truly worldwide audience, so we can all work towards the goal of improving the outlook for patients with kidney disease.” He added “At previous meetings, scientists from Japan saw our results and undertook experiments themselves to confirm and add to our findings. It is amazing to think that work done in Yorkshire is being reproduced and developed in so many corners of the world.”

Dr Mooney said “The response to our work was very positive indeed. Many researchers from around the world sought us out to speak to us about it. It is a long way to come, but it is a unique opportunity to show what we have been doing to a world audience of kidney scientists. All of us really think that this research could lead to new treatments for patients with kidney disease, and without the support of Kidney Research Yorkshire this work would simply not have been possible.”

PAEDIATRIC RESEARCH

A £300,000 legacy left mysteriously to a Yorkshire charity is helping youngsters coping with debilitating kidney diseases.

Kidney Research Yorkshire was left nearly £300,000 in the will of Mary Strang a few years ago..

It is still unclear why, but Mrs Strang, from Bailiff Bridge near Brighouse, stipulated the money must go to the charity to help treat babies and toddlers with kidney disease who were being treated in Leeds.

Clinical Psychologist Simone Friedel, supports children, parents and siblings going through dialysis and with issues around transplants.

Kidney Research Yorkshire asked Simone for an update on her work during the last 3 years.

“The main areas of my job centre around managing the psychological “side-effects” of a chronic or acute medical condition and its management. Renal diagnoses often entail a long-term or chronic course thus requiring families to adjust to the reality of the diagnosis and learn the skills necessary to carry out various forms of treatment at home. For the children and young people themselves they are often faced with various, repetitive, invasive tests that most are naturally frightened off – nobody like needles or blood tests!! My job is broadly to a) help children/young people (YPs) to adjust to the reality of their diagnosis, b) help them learn and develop coping strategies to deal with tests and their treatment, c) help them develop resilience to deal with the significant demands arising from their condition and its treatment, including issues around adherence. (Adherence is the degree to which patients take their medicine as directed).

I’m trained in different therapeutic techniques, including CBT, and over the last 3 years I have received further training in ACT (acceptance and commitment therapy) and compassion-focussed therapy- this gives me a tool kit to help tackle specific problems, ranging from procedural distress (needle phobia) to low mood, anxiety problems, adjustment issues, adherence problems to name a few.

I really enjoy my job – as you can see it’s so varied and gives lots of opportunities for developing things further. I’m lucky to be part of a lovely team who value my work and work collaboratively. Finally, while I often see people who are deeply affected by the impact of their/their child’s renal condition, and it can be hard to see it -after all I’m a parent myself, I feel it is a privilege to walk their journey with them – often from the child’s diagnosis to the point where their condition is manageable/ in remission / post-transplant and seeing how young people can flourish despite the demands on them is very rewarding. I’ve had some really lovely feedback from families and it is nice to know that my work is valued.

If I had one thing to wish for – it would be to have more time to do more”.

Sophie Yates, Clinical Nurse Specialist helps families whose child is on peritoneal dialysis overnight at home, by visiting them at home and providing them with support.

Sophie gave us this update:-

“I continue in my role primarily training and supporting children and their families on Peritoneal Dialysis.  I also help support some of our chronic patients who are not yet at the point of dialysis but may have multiple needs and require support.  The main objective of my role is to keep the children and families at home as much as possible, and reduce the amount of time visiting hospital.

As part of my role I organised two nights away for some of our haemodialysis families and also some of the teenagers (without parents) to Drayton Manor, this was great for our patients and families to meet each other and get a better understanding of the different types of dialysis and transplants.  It also allowed some of our families who may not normally get an opportunity such as this to have a weekend away”.

Dr Maggie Fitzpatrick gave us this report on an eight year old kidney patient being treated with grant support under this legacy.

She is generally doing very well. She had a deceased donor renal transplant in August 2013 having been on peritoneal dialysis for some time before that which was obviously quite a challenge for her and her family. The transplant is now functioning well following a few complications in the early post transplant period. She was 7 in September and is attending school regularly, has a good apetite and is now thriving which is great news. She has unfortunately has some problems recently with urinary tract infections which we are managing but the transplant is still working well for her. She does need to take a number of medications to prevent rejection, needs to maintain a good fluid intake and is also on a small dose of a prophylactic antibiotic to help prevent urine infections.

Investigation into the use of peripheral blood transitional B cells as Biomarkers for renal graft outcomes

Through research funded by Kidney Research Yorkshire, Dr Baker has found that some specific cells of the immune system (transitional B cells) are found in the blood of people with kidney transplants in different amounts, and the number of cells seems to associate with how long the transplant lasts.

It is hoped that this will ultimately lead to personalised treatment – ie different immunosuppression medications given to different patients according to the number of these cells found in their blood.

This could both improve the length of time the transplants last, and avoid giving too much drug to people who don’t need it or too little to those that do. Also, understanding this basic biology will improve our knowledge of how the body responds to transplants and could even lead to novel treatments in the future.

Dr Richard Baker – Leeds Teaching Hospitals NHS Trust

Polyomavirus-associated nephropathy (PVAN)

Polyomavirus-associated nephropathy (PVAN) is a serious, emerging complication in kidney transplant recipients, and is now a leading cause of kidney transplant rejection. It is caused by destructive replication of the BK polyomavirus (BKPyV) in the kidney. This virus establishes a lifelong infection in the host, which remains sub-clinical in healthy individuals. However, in kidney transplant patients, where the immune system is being suppressed by therapeutics to prevent rejection, the virus can grow uncontrolled and cause kidney destruction and disease.

Prevalence of PVAN is increasing and currently afflicts up to 10% of all kidney transplant patients. Presently, there are no effective direct acting drugs targeting BKPyV, and therefore the clinician is faced with the dilemma of moderating the dose of immunosuppressive drugs to allow the patient’s immune system to battle the virus, which raises the risk of kidney transplant rejection. There is a clear unmet need for better therapies for PVAN, and the route to their discovery lies in a better understanding of the molecular mechanisms underlying BK infection.

Using this pilot grant, we wish to test BK virus entry as a potential tactic to intervene in the development of PVAN. We have used existing high-resolution structural information on the interaction between BK virus and its host receptor on a kidney receptor to develop a large number of drug compounds with the potential to interfere with this critical interaction and prevent infection of the target cell. Initially, we will screen a large panel of compounds and subsequently focus on a small number of lead compounds to study in greater detail. Using cell-based assays and structural biology we will determine how these compounds prevent BK infection and then using our expertise in medicinal chemistry we will engineer these compounds to improve their inhibitory properties.

This project brings together skills in the BK virus, kidney biology, structural biology and medicinal chemistry. Using experimental systems developed with Kidney Research Yorkshire funding, this multidisciplinary project aims to directly prime the development of future therapies against PVAN.