Update magazine - Summer 2021 by Kidney Research UK

Update. Summer 2021

Issue 25

The magazine from Kidney Research UK

Four transplants, four rejections – why we’re transforming treatments Page 04 Patient input shapes the future Page 10

Cycling helps heart health on dialysis Page 12

News

Celebrity appearance pays forward childhood luck Comic Rhys James featured in the latest series of Celebrity Mastermind to raise money for Kidney Research UK as a way of saying thanks for an easy recovery after having a kidney removed at the age of 10. © Christopher Thomond, The Guardian

Welcome. It’s my pleasure to guest edit this issue of Update, for Kidney Research UK. It’s a year since I launched the Andy Cole Fund with the charity. With so much going on at this time last year we could have delayed launching the Fund, but it felt really important to put a mark in the ground and say no, things must change. Life is tough for kidney patients, transplants are not a cure and kidney disease can have a really bad impact on our mental health. I know, I’ve been there.

The London-based comedian jumped at the chance to support a charity close to his family’s heart.

Following a series of tests, doctors found one of his kidneys had shrivelled up and failed.

Rhys, 29, who has made a name for himself in programmes like Mock The Week, had to revise 250 episodes of The American Office comedy series as his specialist subject.

“I was told it could happily sit there if need be, but because it was causing so much pain, they advised it was better to take it out.”

Rhys has no kidney issues now, but at the age of eight, he began getting pains in his side and when he was 10 years old the pain had become excruciating.

Just before the first lockdown I was at a dinner talking to potential donors about the Fund, then suddenly the world was completely different.

Removal surgery took place at Great Ormond Street Hospital and he remained under their care for checkups until he was 16. Meanwhile, the remaining kidney is fine and Rhys enjoys good health.

When I was at Great Ormond Street Hospital, I saw kids in the same ward with far more complicated and serious issues. While it wasn’t minor, the procedure I had was done so efficiently and my recovery time was minimal. Doing Celebrity Mastermind was a great chance to pay forward to help others who have not been as lucky.

Like so many others, I’ve dealt with months of isolation and felt pretty anxious while following the news about Covid-19. I’ve been really pleased the charity is doing the hard graft on behalf of patients, and researching how best to protect us from this virus. It really feels like the charity’s got our backs. I was invited to record the charity’s BBC Radio 4 appeal at the end of May. I think speaking up is one of the most important things we can do – how else will more people understand kidney disease and why research is so important? But I know it’s also one of the hardest things to do. The response to the appeal has been brilliant, with people donating and sharing their own stories. So thank you to everyone for your support – and I’d say don’t stop there. If we all get behind Kidney Research UK, dialysis will get better, transplants will last longer, and we can live healthier, happier lives. We all need hope. Guest editor PS Find out more about the Andy Cole Fund here: www.andycolefund.org

Registered charity no. 252892. Scottish charity no. SC039245.

Put your best foot forward and join us for our 2021 virtual ‘My Bridges Walk’ to help keep research going. The popular event will be held virtually, which means you can choose where you walk, who you walk with and at what time. Our Bridges Walks normally see hundreds of people taking part by walking seven miles at their own pace across bridges in London, Glasgow and Newcastle. We may not be able to meet each other in person to celebrate, swap stories and share our passion for research at our Bridges Walks in the normal way, but together, we hope we can share our mission to fundraise for the future.

Cover photo Four time transplant recipient Paul Cookson faces the rest of his life on dialysis. He’s supporting our new campaign, aiming to transform treatments for people with kidney disease.

We need your help more than ever. If you can donate, please visit www.kidneyresearchuk.org/donate

This year we are asking people to set their own challenge to raise funds and help build a bridge towards a cure for kidney disease. Why not surprise us – it could be walking in your front room, the garden, local park or, lockdown restrictions permitting, walking further afield. It could be the perfect excuse to connect with family, friends or work colleagues to raise money for a cause close to your heart. Walk on Sunday 22 August to fund vital research into kidney disease. Your walk, your way! Our number one priority is the safety and welfare of our supporters so please adhere to Government guidelines when completing your challenge. Don’t forget to share your story with us on your social media challenges by using #MyBridgesWalk. To register your challenge, visit: www.kidneyresearchuk.org

Diary dates We hope the following events will take place this year, please keep an eye on our website for details and other ways you can support us. #850Challenge Throughout 2021 #850CycleSportive (new event) July 2021 Skydives Saturday 3 July & Saturday 2 October Six-Tea Party Saturday 24 July & Sunday 25 July My Bridges Walk Sunday 22 August Vitality Big Half Sunday 22 August Glasgow Kiltwalk Sunday 29 August Tour o the Borders Sunday 5 September

World Kidney Day winner

Great North Run Sunday 12 September Virtual Virgin London Marathon Sunday 3 October

World Kidney Day went with a bang on 11 March this year and our joint digital campaign with other kidney charities and professional organisations reached thousands across the UK. People loved our photo competition and shared their favourite pictures with the big yellow kidney to spread awareness of kidney disease.

Virgin London Marathon Sunday 3 October Charity Golf Day, The Belfry Thursday 7 October Kidney Research UK Gala Dinner – The Brewery, London Saturday 9 April 2022

Huge congratulations to Rachel Bartlett McArdle, who won the prize of £250 Amazon vouchers. She posted a fabulous picture of her mum on Instagram, snapped before she donated a kidney to help Rachel’s dad receive one through the paired donor programme.

Andy Cole Fund Gala Dinner – The Dorchester Hotel, London Thursday 3 November 2022

Opening the door to new research ideas We have launched our Open Door initiative to drive new research ideas and transform kidney patients’ lives even more quickly.

Andy Cole

Contact the editorial team Kidney Research UK, Nene Hall, Lynch Wood Park, Peterborough PE2 6FZ 0300 303 1100 pressoffice@kidneyresearchuk.org Website: www.kidneyresearchuk.org Designed by www.adeptdesign.co.uk

Your Bridges Challenge for 2021

As well as our usual research grants funding rounds for researchers, we now want to open up new ways to capture and support ideas to make a difference for people with kidney disease. Anyone – patients, carers, industry, companies, researchers, scientists, doctors or health professionals – can share

their research ideas with us and together, we will explore how to move them forward.

For advice on how best to secure

Here are some examples of the things you could approach us with through Open Door:

You have a great idea for research but

To get advice on how to take your

research to the next stage To seek support with commercialising your product For help building a network of people to work with To approach patients to steer your research idea

funding for your idea are not sure how to make it a reality  “Great ideas can come from anywhere,” said Professor Jeremy Hughes, kidney doctor and chair of our board of trustees. “We’re really excited to see what comes through the Open Door and how we can accelerate discoveries and innovations to make a real difference to patients’ lives.”

disease To make a gift to Kidney Researchkidney UK call: 0300ends 303 here. 1100

Transform treatments

Let’s transform treatments. Over the next three years we are striving to raise £3 million to transform treatments for people with kidney disease. In this and future issues of Update we’ll be telling you why transforming treatments is so vital, about the research we are funding, the research still needed and the people you can help by supporting our work.

aving been through four kidney transplants, four rejections and spent 20 years on dialysis, 43 year old software engineer Paul Cookson from Cambridge needs treatments to improve, fast. Paul has had kidney problems since he was born. He had an operation to reimplant his badly positioned ureter (which carries urine from the kidney to the bladder), but after a urine infection his kidneys failed. He was still just a baby. “I narrowly avoided dialysis as a child,” he explains. “The doctors kept me going with diets and blood transfusions. Then I had my first transplant when I was seven years old. Not a lot of places were doing paediatric renal care, but I was lucky to get transferred to Guy’s Hospital – my dad heard about Guy’s on the radio.”

Survival at stake By the time he was 15 Paul’s first transplant was failing and he needed another new kidney. Immunosuppressants try to stop the immune system attacking a transplanted organ with antibodies. In Paul’s case the antibodies won the fight and his second kidney transplant failed. Thankfully, a third transplant attempt shortly after, in 1993 was successful. Paul went to university, on a strict programme of medication and regular check ups. But eight years on, his third transplant failed and Paul was back to square one, after he contracted shingles encephalitis. “That was quite touch and go,” he recalls. “The shingles had spread to my brain. The doctors didn’t know whether I would actually survive. I did, but my transplant didn’t.”

Mental health impact The shingles had spread to my brain. The doctors didn’t know whether I would actually survive. I did, but my transplant didn’t. Paul Cookson

To make a gift to Kidney Research UK call: 0300 303 1100

Paul now had a big adjustment to make, coping with life on dialysis and it’s not been easy. “I have had depression at times, I’ve also seen a psychologist to help me as well,” he says. “I do the dialysis at hospital in the evenings so I can go to work and do a 9 to 5 job. Most weekends I can get a bit worn out after about 10 hours on the machine in all during the week. “I tend to have a bit of a nap on the machine when I’m exhausted. I have had some issues when my blood pressure has dropped and I can get leg cramps, which can get quite annoying.”

It was 14 years before Paul had his fourth transplant in 2015, aged 38. He had been warned his previous transplants and blood transfusions meant that his antibody levels were now very high, making it difficult to find a matching kidney. Paul says: “My consultant decided they would try removing some of the antibody matching criteria to increase my chances of getting a match, with the plan being to tackle any problematic antibodies after the transplant. I agreed to go ahead.” Sadly, it didn’t pay off, rejection started happening within a week of his operation. Doctors tried replacing the plasma part of his blood containing the antibodies, but his blood became too thin and his blood vessels kept leaking. “The plasma exchanges were risking my life, so they decided to stop,” he explains. “They couldn’t save the kidney. “The chances of me ever having another transplant are probably very slim. Unless some new treatment comes along – you never know where research will go.” Paul is resigned to a life on dialysis, for now. We don’t think this is good enough, which is why we are pledging to transform treatments by: Making kidney transplants last longer Reducing the burden of treatment and monitoring Improving the quality of life for people living with kidney disease E nsuring everyone has equal access to treatments and care. Visit www.kidneyresearchuk.org/ transform-treatments to find out how you can help us ensure that people like Paul have a brighter future.

Giving hope for the future Thanks to vital support from the Stoneygate Trust, we have recently been able to fund six new projects which could prove life-changing, if not life-saving for people like Paul. Here’s a taster of our new grants: Helping transplants last for longer – £237,000 Dr Maria Kaisar and team at the University of Oxford will analyse blood samples from donors to develop a mathematical model to predict how well a donor kidney will function after transplant. The model could help doctors accurately assess kidneys, transplant only the best and identify suitable kidneys from donors previously deemed too high risk.

Tackling low blood pressure during dialysis – £234,000 Professor Nick Selby will tackle the sudden drop on blood pressure some patients experience during haemodialysis by using pressure sensors on the dialysis tubing. He’s working with teams across the University of Nottingham and Derby, Royal Derby Hospital and the University of Derby. This new technology could help doctors predict a sudden drop in blood pressure and prevent unpleasant symptoms and long-term negative effects on patient health and survival.

kidney disease ends here.

Covid-19 vaccines

Offering hope in uncertain times. The last year has been like no other. As a charity, we have faced some really difficult times, and had to make some difficult decisions. But the pandemic has also meant we have adapted to the needs of people with kidney disease and taken opportunities that could make a real difference. We have worked more closely with the professional organisations and charities in the kidney community than we ever have before to protect, inform and support patients facing the dangers of Covid-19.

Dr Michelle Willicombe and Dr Steve McAdoo from Imperial College London, with Dr Ed Carr from Dr Rupert Beale’s lab at the Francis Crick Institute, are studying how well these vaccines provide immunity to Covid-19 infection. They will find out how long this immunity lasts and ultimately how well these vaccines can protect patients by taking samples from 1,200 kidney patients across the UK. This study will begin by investigating how people on haemodialysis respond to the vaccines, and we hope will be expanded to include other groups of kidney patients. “Vaccines are the best way to protect kidney patients,” said Sandra Currie, chief executive of Kidney Research UK.

New study to reveal how well Covid-19 vaccines protect dialysis patients In March, we joined forces with the National Kidney Federation (NKF), Kidney Wales and several kidney patient associations to fund a new research study to discover how well Covid-19 vaccines work in people who go to hospital for their haemodialysis treatment.

To make a gift to Kidney Research UK call: 0300 303 1100

“But with other vaccines, the degree of kidney disease or whether someone is taking immunosuppressants means they don’t always work as well as they should,” she explains. “It’s vital we understand how effective the Covid-19 vaccines are, so patients know if other protective measures are also needed. This information will also help doctors tailor treatment for them – including identifying the best time they should receive booster doses.”

Trial to protect kidney patients prioritised by the Government

We supported the Government’s vaccine campaign

In the last issue of Update, we wrote about the new PROTECT-V trial which we are helping to fund, led by Dr Rona Smith at the University of Cambridge. The trial is testing whether a nasal spray version of the anti-tapeworm drug niclosamide can help protect patients on dialysis from Covid-19.

In March, Kidney Research UK signed an open letter with 21 other health charities across the UK to encourage people with long-term health conditions and their carers to come forward for their Covid-19 vaccine.

Since then PROTECT-V has received urgent public health badging from the Department of Health, which means the trial will be rolled out across the country and therefore more people will have the opportunity to take part. A further 15 sites at hospitals around the UK are recruiting patients to the study, or will be shortly. Talk to your nephrologist to find out whether you can take part in the trial.

Vaccines are the best way to protect kidney patients. Sandra Currie, chief executive of Kidney Research UK

Two of our supporters who have both had a kidney transplant, Louise Carten and Lewis Daniels, explaining why they would have the vaccines themselves. The Government campaign urged people in the cohort six category to come forward for their jab and not to wait for their vaccine invitation letter. Vaccines Minister Nadhim Zahawi said: “I am grateful to the charities who are encouraging more people in [cohort 6] come forward. “The vaccine is our way out of this pandemic and offers the chance to protect yourself and others – that’s why it’s vital that people get their jab.”

Working with the kidney community to provide vaccine information We have worked very closely with the professional organisations and charities in the kidney community to create accurate, reliable information about the Covid-19 vaccine for people with kidney disease. We hope this collaborative approach will signal a new way of working in the future. Using a specially designed training programme, we are also working to get reliable information out to people in communities who are more hesitant to receive the vaccine. Our peer educator volunteers and faith leaders from Christian, Sikh, Hindu and Muslim communities are being empowered by these sessions to hold their own talks and webinars in their communities in the coming weeks. The training has been well received, as our peer educator volunteer and kidney patient Hilaria Asamu commented: “It is important that our community put aside our fears, suspicions and hesitancy about the vaccine.  “We must educate ourselves, and others and ask questions, to help us make informed decisions about taking the vaccine,” she said. “This will help to protect, not only ourselves, but others within our homes and community like me.”  Visit our information page www.kidneyresearchuk.org/ covid19vaccineinfo

The vaccine is our way out of this pandemic and offers the chance to protect yourself and others – that’s why it’s vital that people get their jab. Nadhim Zahawi, Vaccines Minister

kidney disease ends here.

Transplant process

Could fat help make more kidneys suitable for transplant?

Fat has notoriously been given a bad name. But what if it could be used for good? With funding from Kidney Research UK, Dr Rashida Lathan and her colleagues at the University of Glasgow are investigating whether fat cells could repair damaged kidneys and make more organs suitable for transplant.

More donor kidneys are desperately needed

n the UK, over 5,000 patients are waiting for a kidney transplant. Often, if organs come from older, sicker donors, or donors who have died, they don’t function well after transplant or can’t be used because they are too damaged. This is because these kidneys are susceptible to ‘ischaemia-reperfusion injury’ during the transplant procedure – tissue damage caused when blood supply returns to a tissue that has been starved of oxygen. “We have kidneys coming in but they’re too poor quality to use as donor organs,” explains Rashida. “The goal of this research is to repair damaged kidneys so more donated organs are fit for transplant and more patients can have this life-saving treatment.”

Using fat cells as treatment Adipose-derived regenerative cells (ADRCs) are cells that are taken from body fat. They are made up of a mixture of different cell types, including a high proportion of stem cells. ADRCs are already being used in clinical trials to repair other organs, such as heart and liver. After some promising results from animal studies, Rashida and her team believe they may also be able to rescue damaged donor kidneys. The team have developed a rat model that mimics the human ischaemia-reperfusion injury. When they injected just one dose of ADRCs from the rats’ own fat tissue, into their renal arteries, they saw a striking reduction in kidney damage. There are many advantages to using ADRCs to repair kidneys. “These cells are extremely easy to access – everyone’s looking to get rid of fat,” explains Rashida. “Machines have already been developed for easy use within hospitals and they can quickly extract ADRCs from fat tissue, so the whole process

We need your help more than ever. If you can donate, please visit www.kidneyresearchuk.org/donate

of extraction and transplant could be done in the same building on the same day. ADRCs also contain a lot more stem cells than bone marrow, and the fact that these cells can be taken from patients’ own bodies makes it a safer treatment, as you are not introducing something foreign into the body.”

How do ADRCs repair kidneys? Rashida is now investigating exactly how ADRCs improve kidney structure and function. She believes they release (secrete) molecules that signal to surrounding kidney cells. To help her understand which molecules have a therapeutic effect on the kidneys and which cells release them, Rashida has been studying which proteins are being made in individual ADRCs. She has found several potential therapeutic molecules — and many are known to be important for repairing other parts of the body. One question raised by this research is whether the signalling molecules could be a therapy by themselves or whether the actual cells are needed. “We don’t know if delivery is as important as secretion,” explains Rashida. “Our data shows ADRCs accumulate mainly within the glomeruli [filtering units] of the kidney, so that contact and targeting might actually be essential to deliver the therapy.” As well as the rat model, Rashida and her colleagues also work with 3D organoids —miniature kidneys grown in a dish. These are used to test the effects of treatment with either molecules or individual types of cells from the ADRC cell mixture to understand more about the mechanisms involved.

The goal of this research is to repair damaged kidneys so more donated organs are fit for transplant and more patients can have this life-saving treatment. Dr Rashida Lathan too damaged to be used for transplant but donated to research. They will investigate the effect of treating these kidneys with ADRCs as well as normothermic perfusion: connecting the kidney to a machine that flushes the organ with oxygenated blood.

How close is this research to the clinic?

Rashida’s work so far suggests that, along with normothermic perfusion, injecting a patient’s own ADRCs through the renal artery during the transplant procedure may improve both the function of the transplanted kidney and the outcome for the patient.

Alongside the rat and organoid model work, Rashida is also working with Robert Pearson, a PhD student at the University of Glasgow, to test the effect of ADRCs on human kidneys

Although early results are very promising, there are more steps to provide important safety data before clinical studies in people, which we would expect in the next 5–10 years.

kidney disease ends here.

Kidney Voices for Research

Patients with purpose. Patient input has always been important to the charity and new developments this year will ensure patients have an even louder voice. Phil Smith, the outgoing chair of our lay advisory committee, explains

hil Smith’s relationship with research started the minute he finished his first ever clinic session with his consultant, after being diagnosed with IgA nephropathy. He was introduced to two researchers looking for people to take part in a project on exercise funded by Kidney Research UK. Phil was intrigued, and his new vocation as an ‘expert patient’ began. “I went on to help organise the IgA national conference, which Kidney Research UK was funding and gradually got more involved in the charity,” he explains.

Six years on, being surrounded by fellow patients on the committee has given Phil enormous insight into other people’s experiences, which often contrast greatly with his own patient journey. “Basically, I’m perfectly fit and healthy, other than my kidneys don’t work very well,” he says. A pre-emptive transplant meant Phil avoided dialysis. He has just celebrated his third ‘kidneyversary’ and is hugely grateful.

Designing studies with patients in mind Phil Smith

Used to working on committees in his former career in education, Phil was soon asked to chair the charity’s lay advisory committee (LAC), helping to input into charity activities and bring a patients’ perspective.

Phil’s experience has made him determined to fairly represent others in his role, including in designing research studies before they begin. He recalls attending a research project proposal meeting, where researchers planned a kidney biopsy on each patient recruited.

We need your help more than ever. If you can donate, please visit www.kidneyresearchuk.org/donate

“I asked the people in the room, ‘how many of you have had a renal biopsy?’ And none of them had, but I had, and I talked them through exactly what it was. They ain’t pleasant!”

The more people that are involved, the broader the knowledge base becomes, and the more valid the consensus becomes.

After Phil’s recommendation and on discovering the biopsy wasn’t essential, the plans were hastily altered. So were the plans to delay reimbursing patients for their travel expenses, when he pointed out the economic difficulties many kidney patients face. The project group were hugely grateful for his input.

volunteers’ views, Phil and Barry then helped the academics score each bid to decide which the charity would fund.

“I think there’s been a sea change in the research community over the years,” he says. “I think patient participation is now absolutely at the centre of their concerns. Researchers are looking out for people not just to be part of the research, but actually to give a view on it.”

“It’s powerful. The charity won’t take bids forward if patients are unconvinced by them.”

Kidney Research UK has shifted to focus even more on the patient voice, including through its grants review process, Phil says.

Deciding which research gets funding Phil and fellow LAC member Barry Jacobs have been a part of the grants review panel for some time but in the most recent grants round, the involvement of patients in reviewing the research grants applications that the charity receives has been ramped up. The new process means many more lay (patient) views are now included, as well as the scientists’ perspective. In January 2021, 22 of our new research network volunteers reviewed our latest applications. Their opinions were then shared at the formal decision meeting, and using the network

“It’s more democratic,” Phil says. “The more people that are involved, the broader the knowledge base becomes, and the more valid the consensus becomes.

New group strengthens the patient voice Other changes within the newly renamed lay advisory group will also strengthen patient and public involvement within the charity and influence change externally. Group members will link with external networks, boosting the charity’s connections to the wider kidney community and enabling even better partnership working. Phil welcomes this more inclusive approach. He can’t wait to see the community of expert patients grow.

“There’s going to be a broader body of expertise,” he says. “It will give people with kidney disease a greater sense of being part of something that benefits them, their families and other people in the future. It won’t be about them servicing researchers, it will be about them being intimately involved in something which affects their lives.”

Parting thoughts Whilst his time on the LAC has ended, Phil still plans to stay involved in research. It’s something he strongly advocates. “A lot of people go to clinic once every four months, they have their blood taken, and they have a five minute appointment with a nephrologist. And that’s it. But actually being engaged in research is tremendous. You meet other patients, researchers and clinicians. And now when the research is finished you get told ‘this is what we found out, this is what you’ve contributed to.’ And that’s a really good feeling.”

Miranda Scanlan, who has polycystic kidney disease, will head up the revamped lay advisory group. Visit our website to find out more about her and her plans for the future.

Join our Kidney Voices community to see how you can get involved in research: kidneyresearchuk.org/research/ patient-involvement/kidney-voices-for-research

kidney disease ends here.

Heart health

Cycling on dialysis improves heart health. We know that being more active can help reduce the risk of heart disease, as well as helping to control weight, reduce blood pressure and cholesterol, and improve mental health. Professor James Burton

esearchers at the University of Leicester have discovered that cycling for just 30 minutes during dialysis could transform the heart health of patients with kidney failure. Sponsored by the University of Leicester and funded by the National Institute for Health Research (NIHR), the research also revealed healthcare cost savings of more than £1,400 per patient. When balanced against the cost of the exercise equipment, this could result in significant savings for the NHS. The work was published in two journals: Kidney International and Kidney International Reports.

Transforming heart health with exercise In the UK, more than 24,000 kidney disease patients rely on haemodialysis to stay alive. But although it is life-saving treatment, it can also cause long-term damage to the heart, leaving the heart muscle unable to pump enough blood around the body. Heart disease is sadly the most common cause of death in kidney patients receiving haemodialysis. We already know regular exercise is good for our heart and circulatory systems, but until now, we knew very little about the direct benefits of exercise on patients with advanced kidney disease who are on dialysis. Most patients receive dialysis treatment three times a week for four hours each time. In the CYCLE-HD study, patients were offered 30 minutes of moderate intensity exercise on a specially adapted bicycle during each of their dialysis sessions. Patients were then monitored for six months and their hearts assessed using MRI scans.

Improving the heart’s ability to pump A reliable way to measure heart health is to measure the size of the left ventricle: the heart’s main pumping chamber. In kidney patients on dialysis, the extra strain on the heart can mean the wall of this chamber thickens (called scarring), which can reduce its ability to pump efficiently. At the end of the six-month study, the research team discovered that the left ventricles of patients who had cycled during their dialysis sessions had gone back to a more normal size again. Several other aspects of heart health had also improved – they had less scarring and the major blood vessels were less stiff. These factors all

To make a gift to Kidney Research UK call: 0300 303 1100

dramatically reduce someone’s risk of dying from heart disease. “We know that being more active can help reduce the risk of heart disease, as well as helping to control weight, reduce blood pressure and cholesterol, and improve mental health,” said Professor James Burton from the University of Leicester, who led the study. “For all those reasons – but especially because the risk of heart disease is so high – keeping active is particularly important for people on dialysis,” he continued. “By the time someone has travelled to and from the dialysis unit and spent four hours connected to the dialysis machine, there’s very little time to do anything else that day, and this happens three times a week for most patients. James Burton

“Cycling can keep patients active and help to pass the long periods of time they spend attached to their dialysis machines. “This research also demonstrates that this simple intervention keeps patients’ hearts healthy and offsets the major heart risk associated with kidney failure. We hope this research will lead to other studies examining how to introduce it to other dialysis units across the country.” Researchers will now examine if the scheme could be rolled out to benefit patients across the UK.

“The study shows exercise can offer significant improvements to the heart health of dialysis patients which may have a major impact on their outlook.” “We are delighted to have supported this fascinating study,” said Professor Jeremy Hughes, kidney doctor and chair of trustees at Kidney Research UK.

How Kidney Research UK supported this project A number of prize winning medical students were involved in this research, who we funded through an intercalated degree award which enabled them to take a year out of their medical studies to focus on research. These included: Federica Poli, who looked at helping researchers understand how useful a new kind of heart scan is in dialysis patients. Adam Hurt, who evaluated the cost effectiveness and health benefits of exercise interventions in patients with advanced chronic kidney disease, including CYCLE-HD. Clare Tomlinson, who studied the thickening and scarring of heart tissue in patients with advanced kidney disease.

Kristina says yes to cycling! I have been a patient at the Leicester General renal unit now for 42 years. I started in 1977, had my first transplant in 1980. That lasted for 26 years. I returned to dialysis in 2006 and then was lucky enough to get my second transplant in 2017. Before my second transplant I was asked to take part in the study and I thought, great idea. First of all, anything to fill the time while you’re on dialysis is fantastic, but when I thought about the health benefits – it could only be good for my heart, make my legs stronger, help my muscles. So I immediately said yes. I really enjoyed the cycling programme from start to finish. Initially I thought it may interfere with the dialysis machine, but it doesn’t. I could still talk to all the friends I had who were dialysing in the same room as me. And when I got home, after a short sleep I would feel the benefit from it. If anybody is offered the chance to go on the trial, I would say go for it.

kidney disease ends here.

Research round up

Research in action. In April, for the first time since 2019, we were able to fund three fellowships. A combination of cautious spending by the charity during the last difficult year and the continued loyalty of many supporters has enabled us to prioritise getting our research back on track in 2021.

Understanding how kidney transplant patients’ immune systems respond to infection

Understanding blood pressure control

Understanding how kidney cysts form

Whilst we would normally be funding six or seven fellowships each year, this is progress from where we were last year, having to cancel our fellowship interviews when the pandemic struck. These awards are a significant investment in three young scientists, allowing them to take an important step in their careers, so that their work can further our knowledge of kidney disease.

Human cytomegalovirus (HCMV) is a common viral infection and most of us have been infected with it at some point in their lives. Normally, the immune system controls the virus and it generally causes few, if any, symptoms – but it remains silently present in the body after infection.

High blood pressure increases the risk of heart and kidney disease, but we do not fully understand what triggers it. By studying the pathways involved in genetic diseases that affect blood pressure, we may be able to shed light on how blood pressure is regulated.

One in ten people under 50, and one in five over 50 develop fluid filled sacs, or cysts, in their kidneys. Cysts are often harmless, but they can affect how well kidneys work if they become too large or get infected.

Two genetic diseases that affect blood pressure are Gitelman syndrome (low blood pressure) and Gordon syndrome (high blood pressure). Both are caused by defects that alter the activity of SLC12A3: a protein in the kidney that reabsorbs salt from the urine back into the blood. Therefore, SLC12A3 is an important player in blood pressure control and scientists are investigating other molecules that may be involved in regulating its activity.

Cysts are a feature in many kidney diseases, including polycystic kidney disease, the leading genetic cause of chronic kidney disease. We do not fully understand how and why cysts form in the kidney, but we do know that the cells within them divide many times, allowing the cyst to continue growing.

Because people with kidney transplants take drugs to suppress their immune systems and stop organ rejection, they are vulnerable to HCMV infection. Without treatment, HCMV can cause a severe illness affecting many different organs, including the lungs, liver, and bowel. HCMV is particularly dangerous in patients who haven’t been exposed to the virus but receive a kidney from an infected donor. Although these patients are treated with antiviral drugs for 3-6 months after transplant, 50% still go on to have the virus in their bloodstream. Dr Farah Latif from Cardiff University aims to understand how HCMV

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interacts with the immune system in kidney transplant recipients and how the immune system fights this infection. She will examine how molecules called cytokines – the soluble messengers of the immune system – help to control infection in those who receive a kidney transplant containing HCMV, and how the virus has adapted to manipulate cytokine responses in these patients.  Understanding HCMV infection in kidney transplant patients is the first step towards developing new anti-viral drugs to protect patients from this harmful virus. Farah’s work is funded by a £202,000 Fellowship award in partnership with The Stoneygate Trust and supported by the Wales Clinical Academic Track programme from Health Education and Improvement Wales.

Dr Elizabeth Wan from University College London will study patients’ genes to try to understand how SLC12A3 is controlled. She will study the genes of patients and families who have Gitelman or Gordon syndrome, but without the already documented gene faults, to find new genes that may control SLC12A3.   Elizabeth will also use healthy samples from the UK Biobank to see if SLC12A3 gene changes correlate with changes in blood pressure and heart health. This exciting work will help us to understand the pathways that control blood pressure and may reveal new ways to treat it. Elizabeth’s work is funded by a Clinical Training Fellowship from Kidney Research UK for £281,000.

Dr Richard Naylor from the University of Manchester is working out what makes cysts grow. He has previously discovered that the proteins that surround the cells – the matrix – are important in allowing cells within cysts to carry on dividing.  Richard will use zebrafish and human kidney organoids – miniature kidneys in a dish – as models of cyst formation to investigate how changes in these matrix proteins affect cyst growth. This work has the potential to reveal new targets for patient treatments that will improve the lives of people living with cysts in their kidneys. Richard’s work is funded by an Intermediate Training Fellowship from Kidney Research UK for £209,000.

kidney disease ends here.