Update magazine - Autumn 2021 by Kidney Research UK

Bumper 60th anniversary issue!

Update. Autumn 2021

Issue 26

The magazine from Kidney Research UK

A 21st century solution to potassium testing Page 12 Reflections on 60 years of kidney research Page 6

Exciting gene therapy developments for nephrotic syndrome Page 14

News

Ethnicity adjustment removed from NICE chronic kidney disease guideline The latest National Institute of Health and Care Excellence (NICE) chronic kidney disease (CKD) guideline update, released at the end of August, has removed the recommendation to adjust for black ethnicity when estimating how well a patient’s kidneys are working.

Welcome. I’m delighted to introduce your special 60th anniversary issue of Update magazine. Looking through the following pages, I hope you’ll enjoy reading details of how far we’ve come since 1951. I also hope that you can share my sense of pride as we have all played our part in what has been achieved. Since our inception, we’ve contributed major advances to the world’s understanding of kidney disease. And we’ve made life-changing developments in dialysis, transplantation and genetics, among many other areas. You can read about a few of the highlights on pages 6-9. None of this would have happened without brilliant supporters like you. Our birthday is also the perfect time to look forward. We have a bold strategy to lead a revolution in kidney health by 2030. And with your help, our researchers are taking big leaps towards a day when everyone lives free from kidney disease. Every step we take brings new discoveries, and new innovations. From the astonishing achievement in developing gene therapy by Professor Moin Saleem’s team (pages 14–15), to the hand-held sensor Professor Fiona Karet and her team are working on, which will allow patients to monitor their own potassium levels at home (pages 16–17). We have much to be excited about, not just in the future but today, this week, this year. However, some changes can’t come soon enough. Kidney failure continues to be a devastating blow that impacts every aspect of a person’s life, as well as that of their family and friends. Paula and Kirsty’s story on pages 16-17 highlights the disappointment and hope on the road to kidney transplantation that will be familiar to too many people. We’re working to make the struggle and worry that comes with kidney failure a thing of the past. Our current transforming treatments campaign is key to this.

This change will prevent overestimation of kidney function in people from black ethnic groups and enable early treatment for chronic kidney disease (CKD). Estimated glomerular filtration rate (eGFR) is the test most commonly used to calculate how well a patient’s kidneys are working and determine their stage of kidney disease. Until now, NICE recommended applying a correction factor when calculating eGFR in a person from a black ethnic group, a decision based on studies in patients who self-identified as African-American in the USA. Our staff and researchers have been increasingly concerned that the adjustment for ethnicity doesn’t reflect the wide diversity within ethnic groups in the UK and have been pushing for change to the guideline. For some patients, unnecessary adjustments could lead to overestimation of their eGFR,

delayed diagnosis of chronic kidney disease, and a delay in treatment or transplant listing. In the 2021 NICE CKD guideline, the recommendation to adjust for ethnicity has been removed as it is no longer seen as valid or accurate. Dr Aisling McMahon, executive director of research, innovation and policy at Kidney Research UK, said, “Eliminating health inequalities has long been one of our top priorities and we are proud to have been part of the discussions that led to this change which will ensure everyone is treated equally regardless of ethnicity. “Any future research into improving the accuracy of eGFR calculations must ensure that all ethnic minority groups are fully represented.”

Dr Aisling McMahon

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finest professionals, to luxury spa breaks and holidays.

Thank you again for being on this journey with us. Together we are improving the lives of everyone who has, or will go on to develop, kidney disease. We have to keep our foot on the research accelerator.

Choose from a delightful collection of watches, necklaces, rings, bracelets, brooches and earrings set with diamonds, sapphires and rubies made by renowned designers including Bastian, Roberto Coin and Gucci.

“Supporters showed enormous generosity when we ran our first ever auction earlier this year, making a huge difference to our life-saving research in a year when fundraising has been especially challenging,” commented Gemma Howell, head of philanthropy and partnerships. “And I am delighted that the selection of jewellery and experiences we now have on offer will not disappoint!”

Sandra Currie, Chief executive

Alternatively, bid for an experience like no other, from private dining experiences with the world’s most renowned chefs, sports experiences in the company of the

Start your Bonfire Night with a bang – the auction runs from 5-14 November. Visit www.kidneyresearchuk.org for further details.

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

Cover photo Professor Fiona Karet is working with her team in Cambridge to develop a hand-held potassium sensor so patients can monitor their potassium levels at home.

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

Donor hero Jim pushes the boat out Almost two years after donating his kidney to a near stranger, 80 year old Jim Thompson has undertaken a nine-day canoe trip along the Thames to raise money for Kidney Research UK and Dementia UK. Jim and Angela Deighton met by chance at a funeral. Angela, aged 74, had suffered from kidney disease since childhood, and her kidneys failed completely in 2018. Jim and Angela knew each other vaguely – Jim had pruned a plum tree in her garden – but nothing more. However, by the end of the day, Jim had decided he was going to donate one of his kidneys to Angela. Angela, a retired teacher, explained: “When I was 12, I was in hospital for many months. But they got me through and I returned to school. “My kidney function was monitored closely. Once my kidney function got down to 15 per cent in 2018, I chose to go on the transplant list and in the meantime, go on dialysis.” Angela’s daughter Emma wanted to donate one of her kidneys. She was a “perfect match” but sadly her kidneys were found to have scarring and they couldn’t go ahead. Jim knew about Angela’s situation, she explained: “I think he thought I was looking a bit pale and wan. He said to me, ‘Would you like my well-travelled kidney?’ It was an extraordinary thing to happen. He’s not a relative, not even a close friend, just a connection.” Tests showed Jim was a very good match for Angela, and the operation went ahead successfully in August 2019.

Iron treatment decreases risk of heart failure in patients on haemodialysis Jim Thompson

“I’ll feel eternal gratitude to Jim for giving me back my life,” said Angela. “I think he’s the most marvellous person in the world.” Having recovered quickly from the surgery Jim was fit enough to start contemplating his epic solo canoe journey. “My son Ivan helped me enormously, opening locks and going down the towpath on the bike drumming up support from boaters and walkers,” said Jim. “He cycled hundreds of miles in the end.

A whole pub came out to cheer me on! It was really emotional. I came under a bridge and the whole bankside was full of about 100 people cheering and shouting. Angela can now get back to the gardening she loves, and enjoy spending time with her grandchild. Jim said: “I’d give another kidney, but I’ve only got one left!” If you’d like to thank Jim for his extraordinary efforts, it’s not too late to donate to his fundraising page: https://bit.ly/3hOhjD9

New results from a pioneering clinical trial that we coordinated to tackle anaemia in patients on dialysis, show that high doses of intravenous iron can also reduce heart failure risks. The PIVOTAL trial (Proactive IV iron therapy in haemodialysis patients) was led by King’s College Hospital and Glasgow University Clinical Trials Unit and funded by Vifor Fresenius Medical Care Renal Pharma. It compared two different clinical approaches to treating anaemia in 2,141 patients receiving haemodialysis treatment: a high dose of iron or the standard low dose of iron if their iron levels dropped too low. Results showed that a higher dose of iron was safe and led to better patient outcomes than giving a low dose, with reductions in heart attacks, strokes, heart failure and deaths. These results were published in the New England Journal of Medicine in 2019. In the new paper, published recently in the Journal of the American College of Cardiology: Heart Failure, researchers used PIVOTAL data to study heart failure events in more detail. Dr Pardeep Jhund, lead author of the paper, explains: “We found that patients who received a higher dose of iron were 44% less likely to be hospitalised for heart failure. This is important because patients who are hospitalised for heart failure are at very high risk of dying.” The researchers also found that patients who received a higher dose of iron were less likely to have multiple hospital admissions for heart failure. Patients who had suffered with heart failure complications previously, and patients with diabetes were most at risk of heart failure events. Dr Aisling McMahon, executive director of research, innovation and policy at Kidney Research UK, said, “We are hugely proud of everyone who helped to make the PIVOTAL trial happen, particularly the patients who volunteered to participate. This is the largest clinical trial we have ever coordinated and we are delighted to see that it is still providing results that will lead to improved treatments and better outcomes for kidney patients on dialysis.”

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

News

Kidney patient hospital referrals improved A study we funded that discovered a way to help GPs predict which patients with chronic kidney disease (CKD) are more likely to need dialysis or a kidney transplant in the future has directly led to changes in the updated NICE CKD guidelines. In the study, which we funded alongside NIHR Applied Research Collaborations East Midlands, Dr Rupert Major and his team from the University of Leicester modified and tested a tool called the Kidney Failure Risk Equation (KFRE). This is a calculation that uses data collected from patients with CKD, including estimated glomerular filtration rate (eGFR: an assessment of how well a patient’s kidneys are working), the amount of protein in the patient’s urine, their age and their gender, to predict their risk of developing kidney failure within two and five years. The results are then given as a percentage. The updated guideline recommends that GPs now use the KFRE and refer patients to a

kidney specialist if they have a 5% or higher risk of needing dialysis or transplant in the next five years. “I believe the KFRE will empower patients to understand their risk of their kidney disease progressing and in turn identify ways that they can reduce this risk,” explains Rupert. “It will also help doctors to communicate risk. One of the many findings of the study, was that it may also reduce the number of referrals to hospital kidney specialists without affecting the number of cases detected of people needing dialysis or a transplant.” Dr Rupert Major Going forward, researchers must continue to study KFRE, both to ensure that it continues to accurately predict risk as treatments for kidney disease improve, and to further understand how decisions are made based on its predictions.

Exhibition gets go ahead Nineteen months since the pandemic disrupted planning, an art exhibition featuring photographic portraits and compelling stories of kidney patients will take place at the OXO Gallery in London.

“We have devised this project using art and storytelling as a way to portray the strength, vulnerability and resilience of those who are affected by chronic kidney disease, shining a light on some of the challenges they face,” said Maddy. “Our aim is to share thought provoking, inspiring human stories that offer

Next year we’re repeating a number of successful events from 2021 and introducing some new ones. Keep your eyes peeled on our website for more details. We would love to hear about your own event and find out what fundraising activities you would like to see from us. Contact our supporter care team to let us know. Step into Christmas December 2021 New Year New You January 2022 #850Challenge January Quit for a Bit February World Kidney Day Thursday 10 March Spring Tea Party April Kidney Research UK Gala Dinner, The Brewery, London Saturday 9 April Star Wars Day Wednesday 4 May

The Survivors: Life Unfiltered exhibition is the brain child of award-winning photographer and creative director Richard Booth, with copywriter and kidney patient advocate, Maddy Warren, and is jointly funded by dialysis technology company Quanta, Kidney Research UK and Kidney Care UK. Featuring over 30 people affected by kidney disease from different ages and backgrounds including former premiership footballer Andy Cole, it first had life in a digital space when it was launched virtually after the Covid-19 pandemic postponed its tour of public galleries and exhibition spaces across the UK. But now both Maddy and Richard are delighted to share it in the ‘real world’ too.

Diary dates

Skydives June Abseil June London Nightrider 11-12 June

Asif Ali, as featured in the exhibition

a different perspective on the world, as well as to provide important education about kidney health.” The exhibition takes place in the OXO Gallery on London’s South Bank, from 26 October to 7 November, 11am-6pm and is free to attend. If you would like to join a private view event hosted by Kidney Research UK from 6-8pm on 3 November, please email specialevents@kidneyresearchuk.org for details.

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

#850CycleChallenge July/August Great North Run Sunday 11 September (tbc) London to Brighton Cycle Ride Sunday 11 September TCS London Marathon Sunday 2 October Andy Cole Fund Gala Dinner, The Dorchester, London Thursday 3 November

The inside track on the work to protect kidney patients from Covid Miranda Scanlon writes I’ve been the lead of the Kidney Research UK Lay Advisory Group since April this year, but I’ve been a kidney transplant patient for much longer – 15 years in fact! Like so many other transplant patients I was shielding for much of the first year of the Covid-19 pandemic. The NHS Covid-19 vaccination programme brought new hope to clinically extremely vulnerable (CEV) people. We were placed higher up the vaccination list than others our own age and the promise of going back to normality was extremely welcome after the year of isolation. So it was very concerning when evidence began to suggest that some transplant patients weren’t producing any antibodies at all in response to two doses of the vaccine, and others were producing just low levels. As 19 July ‘Freedom Day’ approached, when the government was set to remove most of the remaining restrictions protecting people from Covid, we became aware of a great deal of anxiety amongst kidney patients. Despite being double vaccinated, were we still at risk of Covid - and even more so if others stopped wearing masks and social distancing and Covid rates rose? For many of us, Freedom Day was the day we might once again be imprisoned in our own homes. The worry was especially great amongst those needing to take public transport to work or living with school-aged children. What we needed were facts based on the best and most recent evidence and for these to be translated into clear and consistent messaging for kidney care health professionals and for kidney patients. To do this Kidney Research UK teamed up once again with other members of the Kidney Charities Together (KCT) group – Kidney Care UK, PKD Charity, NKF and Kidney Wales, as well as the UK Kidney Association, the professional body for the UK renal community. In the UK, the Medical Research Council had funded the OCTAVE study to look at vaccine efficacy in immunosuppressed people and Kidney Research UK had joined forces with other kidney charities to fund a similar study for haemodialysis patients. I was invited to a meeting where clinical researchers began to share the early results of their studies with other renal professionals and kidney

charities. It was amazing for me to see the scientists and health professionals discussing and interpreting results that were ‘hot off the press’ and then work together with kidney patients and the KCT communications teams, to decide what advice should be given to kidney patients. The speed at which research was being translated into policy and practice was incredible. As Freedom Day arrived, the KCT group, led by Kidney Research UK, was ready to get the message out to kidney patients – get fully vaccinated, but continue to socially distance and seek advice from your kidney care team if you have any worries. The meetings continued throughout the summer. From the evidence from around the world, including the UK, it became clear that the protection provided against Covid-19 in kidney patients was much improved on being given a third dose of an mRNA vaccine (eg Pfizer-Biotech or Moderna). Our focus changed to begin lobbying the JCVI (Joint Committee on Vaccinations and Immunisation) who make the decisions on who can have the Covid vaccination. There was a period of frustration in August, when everything seemed to grind to a halt. The UKKA had presented compelling evidence to the JCVI about the need for the third dose in kidney patients, ahead of the booster programme, but there was no response. It seemed ironic that while everyone was away enjoying a summer holiday, kidney patients were still left potentially unprotected and stuck at home. With the support of the KCT group, the UKKA therefore published a position statement on 13 August 2021, calling publicly for the JCVI to urgently prioritise the third dose. Again, this was backed up with a co-ordinated social media campaign by all the KCT charities. On 1 September, we were rewarded with the announcement from the JCVI that

For many of us, Freedom Day was the day we might once again be imprisoned in our own homes. immunosuppressed people could have a third dose of an mRNA vaccine as part of their primary Covid-19 vaccination schedule. At the time of going to press, discussions are ongoing about when vulnerable dialysis patients and people at CKD stage 5 can have a further dose as well. Recent research published in the Lancet has shown that haemodialysis patients can also have a poor antibody response to only two doses and there is a fear that these patients – less able to protect themselves due to frequent journeys to hospital for treatment – could be left at risk. As a kidney patient, I want to say how much I appreciate the hard work put in by all of the communications teams in the KCT group, the research teams, all those involved at UKKA, and Charlie Tomson, a Kidney Research UK trustee. It has been such a privilege to be able to work with you all. For the latest information about Covid-19 vaccines, visit: www.kidneyresearchuk.org

kidney disease ends here.

60th Anniversary

years of life-changing research.

1960

1970

1961, charity founded as The National Kidney Research Fund

1970-1973, Prototype Lucas Mk.II renal dialysis machine. © Science Museum, London

Dialysis

Unlike pre-1960, different treatment options are now available to patients. In 2014, we introduced the Dialysis Decision Aid – a tool to help healthcare professionals and patients decide the best form of dialysis treatment to suit their lifestyle requirements.

Dutch physician Dr Willem Kolff, known to many as the ‘father of dialysis’, constructed the first dialysis machine in 1943. With World War II in full force and materials scarce, Kolff was forced to be resourceful, and he used household items, including sausage skins, orange juice cans and a washing machine to make his first contraption to clear toxins out of the blood. Since then, huge advances in dialysis machines, the materials and techniques used to gain access to patients’ veins, and the development of peritoneal dialysis in 1980, have meant that the lives of countless kidney patients have been saved.

Many kidney patients rely on haemodialysis to keep them alive. With our funding, Dr Rukshana Shroff from Great Ormond Street Hospital showed that a newer form of dialysis treatment – haemodiafiltration – is more effective, safer and better tolerated by children than conventional haemodialysis. Whilst dialysis is a life-saving treatment, it is also life-limiting. This year, we launched our ‘Transforming Treatments’ campaign, to improve quality of life for kidney patients and reduce the burden of treatment.

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

This year marks our 60th anniversary: 60 years of fighting to end kidney disease through cutting-edge research; On this important milestone, we have handpicked some of our successes to celebrate together.

1980s, we funded Sir Peter Ratcliffe’s work; he went on to be awarded the Nobel Prize in 2019 1971, Kidney donor cards introduced, the forerunners to the organ donor card. © Science Museum, London

1992, we funded Professor Giovanna Lombardi’s work to prevent transplant rejection

1980

Anaemia We are proud to have accelerated several breakthroughs in the treatment of anaemia, common in kidney patients. This means they don’t produce enough red blood cells and it can leave them feeling exhausted. In the 1980s, we funded research by Peter Ratcliffe (now Sir Peter Ratcliffe). Peter studied how the kidneys control the gene affecting the production of erythropoietin (EPO) – a hormone that stimulates bone marrow to produce red blood cells. This work led to the widespread use of manufactured EPO which has made a significant difference to the lives of kidney patients with anaemia and has enormous

1990

potential to help treat other diseases including cancer. Sir Peter was awarded the most prestigious award in science in 2019 the Nobel Prize.

better for treating anaemia than giving a lower dose and that patients were less likely to die or have heart attacks, strokes or heart failure.

Although EPO has drastically improved the treatment of anaemia, many kidney patients on haemodialysis still require intravenous iron supplementation. Historically there was very little evidence for how much iron is safe and effective to give to kidney patients. Between 2013 and 2018, we facilitated one of the largest renal clinical trials ever undertaken in the UK – the PIVOTAL (Proactive IV iron therapy in haemodialysis patients) trial. The trial, led by King’s College Hospital, in partnership with Glasgow University Clinical Trials Unit, showed that giving haemodialysis patients a higher dose of iron was safe, effective and

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60th Anniversary

Building our community We are proud to invest in talent and fund opportunities throughout the career ladder to enable skilled students to become kidney researchers. However, we know we can’t end kidney disease alone and, especially in the last decade, we have harnessed the power of community by establishing networks, identifying alternative sources of funding and partnering with other charities and organisations to drive change. In 2007, we joined forces with several kidney organisations to establish the UK Kidney Research Consortium (UKKRC), which fosters and drives collaborative research

2017, the first UK kidney biobank launches Since 2010 we’ve funded Professor Mike Nicholson’s work on normothermic perfusion

into kidney disease. In 2016, the UKKRC published the first UK Renal Research Strategy, bringing together professional and patient organisations to identify areas where research is needed to deliver maximum benefits in the health and wellbeing of kidney patients and those at risk of kidney disease. Tackling health inequalities has long been at the heart of our work and in 2019, we drew together experts across the UK to publish a report into kidney health inequalities in the UK showing that certain groups of people are at greater risk of developing kidney disease. This report brought into sharp focus the work needed to address the inequalities that lead to poorer kidney health outcomes. In 2017, we led collaborative efforts to launch NURTuRE (the National Unified Renal Translational Research Enterprise) – the first UK kidney biobank. By collecting and storing biological

samples from 3,000 patients with CKD and at least 800 patients with idiopathic nephrotic syndrome and linking these to clinical data through the UK Renal Registry, this resource will accelerate understanding of kidney disease and development of new treatments. In the last year, the kidney community has been challenged like never before in the face of the Covid-19 pandemic. We responded quickly to this critical need, in partnership with several other kidney charities, by funding two important studies to try to better protect kidney patients from Covid-19. The first investigating how well Covid-19 vaccines work in patients who go to hospital for their dialysis treatment, and the second examining whether a tapeworm treatment can prevent Covid-19 in vulnerable patients. We continue to work closely with these organisations to advocate for kidney patients and understand how best to keep them safe.

2015, Pharmaceutical treatment approved for ADPKD

2010

2000

2020 2020, we supported King’s College Hospital rehab team to launch Kidney Beam, a free online wellbeing service

Transplant Since the UK’s first successful deceased donor and living donor kidney transplants in 1959 and 1960, respectively, we have had a key role in driving huge progress in transplantation research. In 1992, with our funding, Professor Giovanna Lombardi at Imperial College London discovered that specific white blood cells called regulatory T cells (Tregs) might be able to prevent transplant rejection in patients with lupus. Giovanna is now working as part of an international consortium to test whether treatment with Tregs can reduce the number of immunosuppressive drugs transplant recipients require, and early results have shown that this therapy is safe in kidney patients. Since 2010, our funding has enabled Professor Mike Nicholson and his team to develop a pioneering technique to increase the quality and lifespan of kidney transplants and this technique is currently being trialled in patients. The technique, called ‘normothermic perfusion’, involves

flushing the kidney with warm oxygenated blood before transplantation, to revive it and reverse any damage caused by cold storage. This has the potential to repair kidneys that would have previously been deemed too damaged for transplantation, increasing the available pool of donor kidneys.

Normothermic perfusion also offers a unique opportunity to deliver therapies straight to the kidney before transplantation. With our funding in 2020, Dr Emily Thompson from Newcastle University discovered that, when combined with normothermic perfusion, treatment with stem cells, called multipotent adult progenitor cells, can improve the quality and function of damaged kidneys.

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

Genetic discoveries In the last six decades, our knowledge of genetics has come a phenomenally long way, and this has fuelled some life-saving discoveries for kidney patients. In the early 1980s, researchers were beginning to map human disease genes. Dr Stephen Reeders, then a registrar at the Oxford Renal Unit, decided to do the same for autosomal dominant polycystic kidney disease (ADPKD) – a life-threatening inherited condition that can cause kidney failure – and he discovered and mapped the gene PKD1. Seeing the potential in his work, we funded Stephen and his team to investigate how faults in this gene could lead to ADPKD. Decades later, in 2015, as a result of this early research, the first ever pharmaceutical treatment in Europe for ADPKD – Tolvaptan – was approved.

Wellbeing Living with kidney disease is relentless and can inevitably put a huge strain on mental health and wellbeing. Historically this has not been at the forefront of kidney medicine, but we are striving to change that. In 2019, we supported Dr Alex Hamilton from the University of Bristol to conduct the Surveying People Experiencing young Adult Kidney failure (SPEAK) study; an online survey assessing challenges faced by young adults with kidney disease. The results highlighted the emotional impact of kidney disease on young people and Alex is now researching treatments and initiatives used to help young adults with other chronic conditions to see if they could help kidney patients. With the extra challenges the pandemic has brought, focusing on mental health has never been more important. In May 2020 we partnered with the Centre for Mental Health, releasing a statement of intent outlining the actions needed to transform kidney services to support patients’ mental health. During the first Covid-19 lockdown, kidney patients were more isolated than ever.

We supported King’s College Hospital renal physiotherapist, Dr Sharlene Greenwood, to launch and research whether Kidney Beam – a free online wellbeing service for people living with kidney disease – can help patients manage their physical and mental health. In May 2020, England and Manchester United footballing legend Andy Cole set up the Andy Cole Fund with us, to raise money for research into transplants and mental health support for kidney patients.

Long road ahead We have come a long way in 60 years. Treatments for kidney disease have changed dramatically and many people can now live a long, fulfilling life. However, this is not the case for all kidney patients, we still have a long way to go. With your help, in the next 60 years, we will enable early diagnosis of kidney disease and early intervention, transform treatments, and make sure everyone in the country receives the quality of care. Kidney disease ends here.

kidney disease ends here.

Kidney pioneers

Kidney pioneers – personal reflections on the development of UK renal services. In the UK today, over 70,000 people are either on dialysis or have received a kidney transplant. But 60 years ago the medical profession was highly sceptical of these fledgling innovations – and the pioneering renal teams who championed them.

Here, some of the individuals who helped to shape and develop modern kidney care share memories of the path to progress.

Teamwork Early renal teams were often viewed with suspicion by other medical departments because they worked differently, often rejecting traditional conventions. They involved kidney patients in decision making and were the first to develop nurse-led services. “From very early on we did things differently. We asked our nurses to do a tremendous number of things, not just in the dialysis unit, but also on the ward as well. I think we were regarded as thoroughly horrible by a number of people. We had sharp elbows, we occupied space and we took over. We grew ferociously! We ran the renal units as a large family, including the patients. Many non-renal clinicians felt that it was quite wrong and unethical even, to involve patients with the burden of deciding what might be best for them.” Professor Stewart Cameron “We were the first type of nurses to be given that level of responsibility. Now there are many nurse-led services and nurse consultants in a variety of specialties, but it did all start in renal. It was also the first time I’d worked in a situation where the patient was an equal. Renal patients had to do things for themselves, otherwise, they wouldn’t have survived. And they became partners, friends and colleagues.” Sally Taber “More than 40 years on I am still in contact with some of my patients. These were lifelong commitments.” Professor Sir Cyril Chantler

Celebrated nephrologist Professor Stewart Cameron CBE, FRCP spent the majority of this career at Guy’s Hospital and King’s College Medical School, where he helped to develop kidney dialysis and transplantation.

Royal Free Hospital Renal Unit patient and nurse with dialysis machine, 1968.

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

Paediatric nephrologist Professor Sir Cyril Chantler GBE trained at Guy’s, Hammersmith and Great Ormond Street hospitals. While at Guy’s, he helped to devise a method of measurement of kidney function in children. He later researched diet and growth failure in children with renal impairment, helping to establish paediatric nephrology as a clinical specialty.

Innovation and determination The 1950s and 60s was a time of great innovation when the first bulky dialysis machines and the beginnings of renal transplantation began to offer hope to kidney patients. However, life on early dialysis was very hard and in 1969-70 deadly outbreaks of hepatitis B, which claimed the lives of hospital staff and patients, threatened the permanent closure of renal units. But teams persevered, developed new ways of working and accelerated the rollout of home haemodialysis. “It was a fascinating time – a time of excitement, seeing chronic renal failure reversed by transplantation and by dialysis. And the patients were very courageous; they knew they were in new worlds.” Professor Sir Netar Mallick “After the hepatitis outbreak some people in the rest of the hospital thought that the programme should come to an end. But the renal unit went on and that was mainly due to our Senior Sister who had a tremendous capacity for keeping cool and keeping the morale of the nurses up.” Dr Anne Lambie Sometimes nephrologists had to take matters into their own hands to force change. Professor Sir Cyril Chantler recalls how he went public in the 1980s to force the Government into funding a nationwide dialysis and transplant service for children. “I can remember appearing on Panorama with a little clip saying, ‘we can treat children in renal failure, but the Government is not prepared to pay for it’. Which didn’t make me very popular, but that’s what we did.” Professor Sir Cyril Chantler

Professor Sir Netar Mallick is professor emeritus of renal medicine in Manchester. He planned Cardiff’s first renal unit, was associate director of Manchester’s renal transplantation unit from its inception in 1968 and developed an internationally recognised department of renal medicine integrated with the transplantation service. Accomplished renal clinician and researcher Dr Anne Lambie began her medical training at just 16 in 1945 and was based in Edinburgh for the majority of her career. She witnessed dialysis and kidney transplantation in its infancy. A committed teacher, she later helped to reform the curriculum for trainee doctors.

Now there are many nurse-led services and nurse consultants in a variety of specialties, but it did all start in renal. It was also the first time I’d worked in a situation where the patient was an equal. Renal patients had to do things for themselves, otherwise, they wouldn’t have survived. Sally Taber

Inspiration Looking back over their careers, all our pioneers are agreed that their determination and inspiration came from the bravery and resilience of their patients. “I feel so proud to have been involved in the early days. A lot of the progress we witnessed was down to the resilience of patients – to actually go through all that they did, and still say, ‘life is well worth living, let’s keep going with it’.” Sally Taber

As a student nurse, Sally Taber cared for some of the UK’s first dialysis and transplant patients, becoming (arguably) the UK’s first transplant coordinator. She helped to establish the European Dialysis and Transplant Nurse Association and was instrumental in the development of the Transplant Games. She was president, open section, of the Royal Society of Medicine and was chair of trustees at Kidney Care UK.

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Potassium sensor

Empowering kidney patients to monitor potassium levels. At Kidney Research UK, we are determined to push research beyond the discovery stage to the point where it can make a difference to kidney patients’ lives.

We were awarded two Kidney Research UK grants, which enabled us to progress to the point where we needed a lot more investment. Professor Fiona Karet

e caught up with Professor Fiona Karet, professor of nephrology at the University of Cambridge, honorary consultant at Addenbrooke’s Hospital, and former Kidney Research UK trustee, whose work is nearing implementation. With help from our funding, Fiona and her team are developing a hand-held device to quickly and simply measure potassium levels to empower kidney patients to monitor their own potassium.

Why are potassium levels important? Potassium plays a crucial role in the body – it helps to balance blood pressure and supports nerves and muscles. In healthy individuals, the kidneys control potassium levels. But if the kidneys are not working properly, levels of potassium in the body can become dangerously high, or in some patients low, and this can be fatal. Low potassium causes symptoms such as fatigue, weakness, cramps or seizures, but if potassium levels get too high, people generally have no symptoms until it is too late. There is currently no way for kidney patients to measure their own potassium levels – they can only be measured via a blood test at the hospital or GP surgery. This is timeconsuming, costly, and can give inaccurate readings if there is a delay between taking the sample and carrying out the analysis. This means that often patients must take precautions that affect their quality of life, such as eating a low potassium diet, without knowing whether they are necessary.

Transforming potassium monitoring In her clinic, Fiona saw many patients suffering due to potassium imbalances with no means of managing their condition themselves. From what they told her, she realised that this was a huge unmet clinical need and had the idea to produce a handheld device for measuring potassium. A simple finger-prick test, much like diabetic patients use to measure their blood glucose, would allow patients to monitor their potassium levels instantly and adjust their diet and medication accordingly. As well as enabling patients to monitor their potassium at home, the device would be valuable in many situations. “GPs, cardiologists and dialysis units could use the device for immediate results. It could also be used to plan medication schedules, so patients only take medications in the time windows where they absolutely need them,” Fiona explained.

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Developing the device

Patient driven

With our funding, Fiona and her team set about developing the sensor. “We were awarded two Kidney Research UK grants, which enabled us to progress to the point where we needed a lot more investment,” Fiona explained. To further develop and manufacture the device, and with our help, the team set up a spin-out company – Kalium Health.

Although the work is hard, Fiona and the team remain driven by kidney patients, who are vocal about how this device will change their lives.

The device includes single-use test strips which measure potassium from a drop of blood in only one minute. “Blood is drawn through a small tube into the test strip which has a potassium-sensitive chemical on an electrode system.” Fiona explains. “This generates an electrical signal which gives a readout telling you the potassium levels in the blood.” Although the concept is simple, development of the sensing technology has been far from straightforward and has required a truly multidisciplinary approach, “We’ve got chemists, physicists, engineers and clinicians working on this,” Fiona explains. The team have made fantastic progress but there are more steps – which Fiona predicts could take another two to three years – before this device reaches patients. They are beginning to test their prototype devices with human blood samples from healthy volunteers, which will be followed by samples from patients. These initial studies are checking that the blood sampling method is robust and that the device gives accurate enough and reproducible results. The next steps will then be to test the device in clinical trials to get regulatory approval for patient use.

Patients involved in developing this research said: “Being able to measure my potassium level would make a huge difference to my life because it would put me in the driving seat.” “This would literally change my life. I could plan my day, schedule infusions, adjust supplements and medications at the first sign of change on the meter instead of after I crash.”

Fiona has been a loyal supporter of ours for many years ever since she began her impressive academic career with one of our training fellowship awards, and she remains deeply appreciative of the support from the charity. “This project would never have started without Kidney Research UK’s funding. It was a leap of faith for the charity, and I and my team are hopeful it will be well repaid!” she says.

Get involved with our transforming treatments campaign featuring Fiona and other inspiring researchers, visit: www.kidneyresearchuk.org/transform-treatments

kidney disease ends here.

Gene therapy

A giant leap for gene therapy.

How gene therapy works Nephrotic syndrome is caused by a single faulty gene. In simple terms, gene therapy involves replacing the faulty gene with a healthy one, essentially curing the condition. But, as you can imagine, this is a hugely complex and challenging process with lots of unknowns. To get the healthy gene into the kidney cells, you need something to transport it there. A virus is the best way to introduce replacement genes into a cell nucleus, as viruses are excellent at breaking into cells. The team used a specially engineered virus that doesn’t cause disease and doesn’t replicate inside a cell, so it doesn’t pose any danger.

A research breakthrough made possible with Kidney Research UK funding could herald the beginning of the end for genetic kidney disease.

n 2015, Kidney Research UK said “yes” to a funding proposal from a young PhD student – Dr Wen Ding, who was working under the supervision of Professor Moin Saleem at the University of Bristol. The team wanted to investigate whether gene therapy could be used to treat childhood genetic kidney disease. We shared Moin’s belief that there was huge potential in this research and awarded £184,000. That potential is now being realised.

An ambitious proposal Wen’s research project was the first of its kind. Moin explained: “While there have been some very notable successes using gene therapy to treat some disorders affecting the eye, liver, brain and muscles, no one had yet succeeded in using it to target kidney disease.” The target of the research was genetic nephrotic syndrome. It’s a devastating childhood kidney disease that causes the filtration structures in the kidney to start breaking down from birth. Protein molecules leak through the damaged structures, causing further damage. The child’s kidneys usually fail within their first 3–5 years.

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

“The biggest hurdle though,” Moin explained, “is getting the healthy gene into the right cell. If it goes into the wrong cells, it is at best ineffective and at worst threatens side effects.” The right cells in the case of nephrotic syndrome are the podocytes, which form one of the kidney’s filtration layers. To get the replacement gene to the podocytes, the team created a ‘promoter’ which is like a genetic address. It makes sure that the gene is delivered to where it’s supposed to be, and is not lost on the way.

The results Finding the right virus to use, the right promoter, and the right dose to administer involved many experiments, but over four years of dedicated work overseen by Moin, Wen homed in on the right combination. Moin said, “After a few weeks of treatment, Wen’s mouse model showed a significant drop in the amount of protein leaking through the podocyte filtration layer into the urine. That was the moment when we knew that this therapy could work.” This was huge. A career defining moment for a young researcher and a thrilling one for the rest of the world. The outstanding results got the attention of a commercial partner capable of taking the research to the next stage.

Big investment Recognising the potential of the team’s breakthrough, Syncona – an offshoot of the Wellcome Trust, has now invested £45 million in developing the gene therapy further. Moin will be chief scientific officer of the newly formed Purespring Therapeutics, working alongside Professor Gavin Welsh, Associate Professor of Renal Medicine at the University of Bristol. “The next steps are to take the treatment into clinical trials,” Moin said. “That involves large-scale, clinicalgrade manufacturing of the treatment. It’s not a trivial thing to do, to get the purity, reliability and volume that you need. This is something that Syncona have lots of experience with.” Syncona’s involvement means that human clinical trials could be underway in as little as three years. Soon after, we hope to see this treatment made available to patients.

Huge future potential The results of Wen’s project will soon be published. Wen said: “I’d like to say a huge thank you to everyone who donates to Kidney Research UK. My project wouldn’t have happened without their support, and it could make a huge difference to people in the future.” This is just the beginning for gene therapy as a treatment for kidney disease. The Bristol team’s discovery lays the foundation for future transformational treatments. “It’s a very ambitious programme of work we’ve begun with Syncona,” Moin said. “And not just to tackle rare kidney diseases caused by a single faulty gene, but to tackle more common diseases in the kidney too.” We’ve all got a lot to be excited about for the near future.

The biggest hurdle though is getting the healthy gene into the right cell. If it goes into the wrong cells, it is at best ineffective and at worst threatens side effects. Professor Moin Saleem

Find out more about our latest research discoveries by visiting: www.kidneyresearchuk.org

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Kidney transplantation

It’s so important for research to help people like Paula with complex antibodies, as the chance of a transplant becoming available is so slim. Kirsty Vaughan

mum of five from Cheshire is holding out hope for a kidney transplant after her potential donor – another mum of five – was also diagnosed with kidney disease. “I was heartbroken and felt like I had let Paula down, despite my own diagnosis,” said Kirsty Vaughan, 47, a business owner from Gwynedd, who first met friend Paula Carberry at antenatal classes 26 years ago. Paula, 52, was first diagnosed with chronic kidney disease after the birth of her fifth child. She initially didn’t notice any significant problems. However, five years on, things started to deteriorate. “I had been referred to the renal department at Manchester Royal Infirmary and I wasn’t coping well,” explains Paula. “Having to face planning what treatment I wanted in future, all that took its toll.” Starting on dialysis helped Paula feel better. She was able to get back into work, eventually moving on to an investment and pension company. Dialysing at home each night has normalised things but is hard. “Obviously it does affect the children as I haven’t got the energy to do things I’d like to. That puts extra pressure on my husband.”

to be a donor I wouldn’t have known until symptoms presented themselves and irreversible damage could have been done. It turns out Paula could have saved me instead of the other way round.” “I was worried for Kirsty,” Paula admits. “But hopefully they’ve caught it early so her problems can be managed with check ups and monitoring.” Paula recently received a call out of the blue – a kidney had become available from a deceased donor. She dashed to the hospital to prepare for a transplant but sadly was told a few hours later that the kidney wasn’t good enough. “I’m trying not to think about being on dialysis for the rest of my life,” says Paula. “You have to have hope and carry on as best you can.” Their hopes lie in research, Kirsty added: “It’s so important for research to help people like Paula with complex antibodies, as the chance of a transplant becoming available is so slim.”

A successful transplant is far from straightforward. Family members offered to donate, but they weren’t a match. Tests showed that Paula’s antibody levels were very high, and doctors explained that they would cause her to reject 99% of potential kidneys. One weekend during a rare girls’ night out in 2019 Paula explained to Kirsty why she had to take it easy. “Before that, she’d kept it to herself,” Kirsty recalls. “She said at any time she could get a call to say a donor kidney was available, and then I realised just how serious it was.

Kirsty Vaughan

“I thought she’s got a grandchild, she had another on the way. She’d been a massive friend for a very very long time, so I thought I could help her and offered to donate my kidney.”

A tough road to transplantation. Antibody sensitivity and donor health are two of the biggest hurdles in kidney transplantation. Mums Paula and Kirsty explain why we need to transform treatments, fast. To make a gift to Kidney Research UK call: 0300 303 1100

“I’m still very disappointed I can’t donate,” says Kirsty. “I’m doing OK. I’ve made a few lifestyle changes and am going for regular check ups. If I hadn’t been tested

Tackling antibody sensitivity If someone is exposed to foreign tissue types, perhaps during pregnancy or if they have had a blood transfusion or a transplant, their immune systems will have developed human leukocyte antigen (HLA) antibodies. On joining the transplant waiting list, people have their HLA antibodies measured and compared with those of the general population. If a patient has antibodies against the tissue types found in more than 85% of the population, they are deemed ‘highly sensitised’. They cannot be matched with people with these tissue types as their antibodies will attack them. With our funding, consultant nephrologist from Cardiff University Siân Griffin is leading the ITOPS trial to test a strategy to lower highly sensitised patients’ antibodies and increase their chances of having a successful transplant. The team enrolled 26 patients from Cardiff, Leeds and Bristol and patients were either given standard care – or a combination therapy to try to decrease antibody levels. Antibodies are made by immune cells called plasma cells, which develop from B cells. Remove a patient’s antibodies and their plasma cells will just make more. Patients in the trial were given a combination therapy of the drug rituximab to reduce the number of B cells and the drug bortezomib to target the plasma cells that release antibodies.

Kirsty went through rigorous tests over 14 months. They gradually seemed to be getting closer to their goal – until one final test. In a devastating blow, it was shown that Kirsty was actually in the early stages of a kidney disease herself called IgA nephropathy, and wouldn’t be able to donate.

Paula Carberry

The results from the trial are now being analysed and will be ready to share later in the year.

For more about developments to help highly sensitised patients – and how you can help us transform treatments, visit: www.kidneyresearchuk.org/transform-treatments

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Research round up

Research in action. Earlier this year, thanks to vital support from The Stoneygate Trust, we were able to fund new projects with the potential to either detect kidney disease earlier or transform people’s experiences of dialysis or transplantation.

Identifying kidney disease early in high-risk communities

A virtual reality tool for dialysis training

The eye – a window to the kidney

A simple urine test to spot kidney transplant problems

Kidney disease is more common in minority ethnic communities and people living in deprived areas. It is often without obvious symptoms until it becomes serious, when treatment options are limited.

When the kidneys fail, dialysis can help people stay alive. Dialysis can be done at home as well as in hospital, but this can be daunting.

The most common way to detect kidney disease is to measure the levels of the waste product creatinine in the blood. However, creatinine levels only become abnormal when over 50% of kidney function is already lost. Diagnosing earlier will help people receive treatment sooner.

A donor kidney, once removed, goes without oxygen until it is transplanted. This can cause damage to the kidney tissue so it doesn’t work straight away in the recipient (‘delayed graft function’), increasing the risks of rejection and poorer long-term function of the transplanted kidney. Currently, a kidney biopsy is often needed to test for delayed graft function and rejection. This painful procedure is carried out under general anaesthetic and can lead to complications such as bleeding and, occasionally, loss of the new kidney.

Dr Kate Bramham at King’s College Hospital is researching new cost-effective ways for people from high-risk groups to detect kidney disease early and look after their kidney health. Having protein in the urine can be a sign of kidney disease, and high blood pressure is common in people with early kidney disease and in people from minority ethnic and socio-economically deprived communities. Kate and her team are investigating whether a home urine test using a smartphone app could help detect protein in the urine in 2,400 patients with high blood pressure from six GP practices in south London and identify kidney disease before it becomes more serious.

Dialysis is a practical skill that requires training and the tasks involved need repeating many times. With around 100 children starting dialysis each year across the whole UK, the chances for families of children with kidney failure to learn from each other are limited. It is also hard for nurses to get enough experience performing dialysis procedures in children.  Dr Ben Reynolds, his team at the Royal Hospital for Children in Glasgow and Professor Vassilis Charissis and his team at Glasgow Caledonian University, are developing a virtual reality tool to provide guidance and training for nurses, people on dialysis and their families.

The team will also investigate whether interventions from trained people from the same community or ethnic background can improve patient participation.

The tool will transport users to a virtual dialysis environment with machines and equipment. With subtitles available in different languages, the tool will give users the chance to gain ‘hands-on’ training and support for problem scenarios.

The results will inform the design of a larger study to test whether this approach holds the key to spotting kidney disease earlier and is cost effective.

This new tool could allow patients choosing between different dialysis methods to virtually experience these and make a more informed choice.

Kate’s research is funded by an award of £210,000 in partnership with The Stoneygate Trust.

Ben’s research is funded by an innovation grant for £50,000 in partnership with The Stoneygate Trust.

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

Dr Neeraj Dhaun (Bean) and his team at the University of Edinburgh have discovered that people with kidney disease have thinner layers at the back of the eye – in the choroid and the retina – and this thinning relates to the amount of kidney damage. Using new imaging technology called optical coherence tomography (OCT), Bean and his team will investigate if the eye can be used to predict kidney disease progression.

Dr Tim Bowen and his multidisciplinary team at the Wales Kidney Research Unit, Cardiff University, are working on a new test that could predict delayed graft function without the need for a biopsy.

The team will perform OCT scans on a group of patients with chronic kidney disease over five years to examine whether OCT measurements are linked to patients’ outcomes. They will also investigate if the rapid kidney function improvements seen in patients who receive a kidney transplant, and kidney function loss in those who donate a kidney, are also reflected in their eye measurements.

The team has discovered samples from kidney transplant patients with and without delayed graft function have different levels of molecules called microRNAs which can predict the risk of delayed graft function in patients. Tim and his team have developed a method to electrically detect microRNAs in urine and now aim to make a simple dipstick probe that detects microRNAs in urine samples.

This project could reveal a new way to monitor and detect kidney disease early, when treatment is more likely to work better.

This research could provide a quick, reliable clinical test for delayed graft function that avoids unpleasant biopsies.

Bean’s research is funded by an award of £200,000 in partnership with The Stoneygate Trust.

Tim’s research is funded by an Innovation Grant for £50,000 in partnership with The Stoneygate Trust.

kidney disease ends here.

Write your Will for FREE

For those we’ve lost. A gift in your Will helps our researchers end kidney disease sooner. We’ve teamed up with Farewill to offer you a free Will writing service. You don’t have to leave us a gift to use the service but please consider us if you can. Visit farewill.com/update21 to setup your free Will today.

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