Paediatric Nephrology Clinical Study Group
Children can experience many forms of kidney disease from before birth up to their transition into adulthood. Children may be affected by acute kidney injury, anaemia, cardiovascular consequences of kidney insufficiency, glomerular and tubular abnormalities.
There are currently nearly 1,000 children in the UK who are receiving kidney dialysis or have had a kidney transplant. Children are much more likely to experience the consequences of inherited genetic kidney conditions which although rare individually (less than 1 in 2,000 population), account for several childhood kidney conditions and can be highly debilitating.
In addition to the specific symptoms of renal diseases children experience, they are also developing emotionally, physically and academically during this period and require these needs also be taken into consideration. Research is crucial to improve the outlook and quality of care for children with renal conditions.
Who we are
The Paediatric Nephrology Clinical Study Group is co-chaired by Dr Manish Sinha, Evelina Children’s Hospital, London and Dr Ben Reynolds, Royal Hospital for Children, Glasgow.
Group meetings
We have regular meetings to provide overview and support for all forms of research within paediatric nephrology, In addition to CSG leads, the following colleagues have agreed to act as research leads for their Centres:
- Tamara Mallett – Belfast
- Mordi Muorah – Birmingham
- Wen Ding– Bristol
- Shivaram Hegde – Cardiff
- Manish Sinha – Evelina
- Ben Reynolds – Glasgow
- Louise Oni – GOSH/ Liverpool
- Joseph McAllister – Leeds
- Rachel Lennon – Manchester
- Michal Malina – Newcastle
- JJ Kim – Nottingham
- Matt Harmer – Southampton
We also have specific membership for sub-groups focusing on cystic disease, glomerular disease, transplantation, acute kidney injury, CKD and dialysis.
Our aims:
To improve the renal care and treatments of children with kidney problems.
Our challenges:
- Funding
- Study size (as the majority of conditions are rare diseases) and therefore the need for multi-centre (even international) studies
- Support for setting up studies – local infrastructure often saturated with clinical studies.
Key completed studies:
PREDNOS - This study compared two prednisolone regimes in 237 newly-presenting children with nephrotic syndrome. Led by Professor Nick Webb and funded by NIHR HTA following a pilot funded by Kids Kidney Research and Kidney Research UK, it was published in the BMJ. There was no clinical benefit of extending the initial prednisolone regimen from 8 to 16 weeks.
PREDNOS 2 - This study compared 6 days of prednisolone 15mg/m2 vs placebo at time of upper respiratory tract infection to reduce incidence of disease relapse. Led by Professor Nick Webb and Dr Martin Christian and funded by NIHR HTA, the study recruited 365 UK subjects – making it the largest ever RCT in childhood nephrotic syndrome, and was published in JAMA Paediatrics . There was no benefit of a short course of low-dose prednisolone on the rate of relapse associated with respiratory tract infection.
HOT-KID - This study examined optimal blood pressure control in children with chronic kidney disease. Led by Dr Manish Sinha (Evelina Children’s Hospital) and funded by the British Heart Foundation, the study recruited 124 children with kidney disease and 140 controls. Results were published in the Lancet. Intensive (aiming <50th centile) blood pressure control was associated with less cardiac remodelling.
IKID - This study compared a novel infant haemodialysis/haemofiltration machine with other renal replacement therapies in infants weighing <8kg. Led by Dr Heather Lambert (Great North Children’s Hospital, Newcastle), and funded by NIHR/MRC EME programme, the study recruited 35 children and 62 controls, and was published in Pediatric Critical Care Medicine. The NIDUS delivered safe accurate fluid removal and may have a role in future kidney replacement therapies.
3H - The HDF, Heart and Height study compared different ways of dialysing children with kidney failure. Led by Dr Rukshana Shroff (Great Ormond Street Hospital, London) and funded by Kidney Research UK, 190 children on dialysis were recruited, published in JASN. Haemodiafiltration offers several benefits for cardiovascular health compared to conventional haemodialysis in children as well as adults.
ECUSTEC - This study examined the role of Eculizumab in Shiga-Toxin E. Coli Haemolytic Uraemic Syndrome (STEC HUS). Led by Dr Sally Johnson, Great North Children’s Hospital, Newcastle) and funded by NIHR/MRC EME programme. Recruitment was paused and funding withdrawn during the Covid-19 pandemic so insufficient numbers were reached to draw firm conclusions. However, there was no clear demonstrable benefit of eculizumab on disease severity in STEC-HUS
4C - The Cardiovascular Comorbidity in Children with Chronic Kidney Disease study is an international study led in the UK by Dr Rukshana Shroff, funded by NIHR and Kidney Research UK. It has recruited 707 children with CKD across 55 centres in 12 countries. Multiple analyses are ongoing; baseline data was published in CJASN. High clinic blood pressure was associated with all other surrogate markers for cardiovascular disease in CKD.
PLUTO - This study aimed to determine whether the incidence of abnormal and dangerous plasma electrolyte levels in paediatric renal transplant recipients was different with the use of PlasmaLyte -148 compared to intravenous fluid with current standard composition. Led by Dr Wesley Hayes, Great Ormond Street Hospital, London, this was published in Kidney International in 2024. Use of PlasmaLyte-148 was associated with fewer changes in fluid prescriptions, and hyperchloremia and acidosis were less common.
Active ongoing studies:
ATTOMic - (Access to Transplantation and Transplant Outcome Measures in children) aims to clarify barriers to equity of access to kidney transplantation for children and young people and establish the true economic costs impact of dialysis and transplantation on health status and quality of life. This information will be used to improve counselling for prospective renal transplant recipients and understand why kidneys are allocated differently in the 13 children’s kidney units. Led by Dr Stephen Marks, Great Ormond Street.
BioPTiC – (Biomarkers for Pediatric Transplantation in Children (BioPTiC)) is a national study and resource with protocol for biobanking of samples before, during and after paediatric transplantation with ethical approval obtained for all 13 paediatric nephrology sites (including 10 units that perform paediatric kidney transplantation and other sites for paediatric solid organ transplantation and follow-up of patients longer term). Led by Prof Stephen Marks, Great Ormond Street Hospital for Children NHS Foundation Trust.”
KidneyBEAMKids – Following the success of the online platform Kidney BEAM in encouraging and supporting physical activity in adults with kidney diseases, this study aims to test the feasibility of a trial with a similar online platform aimed at children and young people around the time of transplantation.
DINKY – Multi-European centre trial investigating the utiity of a new medication, imlifidase, in children who are highly sensitised to permit transplantation
Cal-Bal - Calcium Balance studies in children with CKD and on dialysis led by Dr Rukshana Shroff, Great Ormond Street Hospital.
Studies in development:
LIMITS – A follow-up study to the PLUTO trial, this study will randomise children at the time of transplantation to receive either institutional standard of care fluid delivery, or will provide a fixed amount of fluid to be delivered each day in the early post-transplant period. This study will hopefully commence early 2025.
NURTURE-AKI – Following the success of the Nurture-INS biobank, this study will aim to collect blood and urine samples at multiple fixed timepoints in children undergoing significant heart surgery who are at high risk of having an acute kidney injury. These samples will form a new biobank that will be accessible to researchers all over the world working on acute kidney injury. This study will hopefully commence early 2025.
Impact:
PREDNOS – since the trial showed no clinical benefit of an extended prednisolone course, patients will be able to take a shorter course and lower overall dose of prednisolone (steroids). This is important as it may mean reduced side effects such as mood and sleep disturbance and increased appetite.
PREDNOS 2 – steroid courses are no longer given at the time of URTI, reducing overall steroid exposure in childhood
3H – haemodiafiltration is often the first modality of choice for children on HD
Anticipated impact:
HOTKID – we think that tighter blood pressure control in children with CKD improve long term cardiovascular outcomes (an important cause of poor health in adults who have had CKD as children)
IKID – if effective, the NIDUS machine will improve the options for dialysis in critically ill infants
ECUSTEC – if eculizumab is effective in STEC HUS, children may require less intensive treatment and have better kidney function in the long term after STEC HUS
Grants:
Programme grants - NURTuRE (National Unified Renal Translational Research Enterprise): MRC stratified Medicine: Prof Moin Saleem PI.
Personal awards - Richard Coward MRC senior fellowship; Rukshana Shroff NIHR Clinician Scientist; Rachel Lennon Wellcome senior fellowship; Lucy Plumb Clinical PhD fellowship NIHR.
Publications:
Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study. Shroff R. et al; J Am Soc Nephrol. 2019 Mar 7.
Hemodiafiltration is associated with reduced inflammation, oxidative stress and improved endothelial risk profile compared to high-flux hemodialysis in children. PLoS One 13:e0198320, 2018. Agbas et al
Effect of haemodiafiltration vs conventional haemodialysis on growth and cardiovascular outcomes in children - the HDF, heart and height (3H) study. BMC Nephrol 19:199, 2018. Shroff R et al
Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: phase III randomised controlled trial and economic evaluation. BMJ 2019; 365 Webb et al.
Evaluation of low dose daily prednisolone during upper respiratory tract infection to prevent relapse in children with relapsing steroid-sensitive nephrotic syndrome. JAMA Pediatr 2022;176: 236-243 Christian et al
A pragmatic open-label, randomized controlled trial of PlasmaLyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO). Kidney International 2024; 105(2): 364-375. Hayes et al
Efficacy and safety of eculizumab in children with Shiga-toxin-producing Escherichia coli haemolytic uraemic syndrome: the ECUSTEC trial. Efficacy and Mechanistic Evaluation 2024; 11. Ives et al
Intensive compared with less intensive blood pressure control to prevent adverse cardiac remodelling in children with chronic kidney disease (HOT-KID): a parallel-group open-label, multi-centre, randomised controlled trial. Lancet 2023; 7: 26-36. Sinha et al
The Infant Kidney Dialysis and Ultrafiltration (I-KID) study: a stepped wedge cluster-randomised study in infants, comparing peritoneal dialysis, continuous venovenous haemofiltration, and Newcastle Infant Dialysis Ultrafiltration System, a novel infant haemodialysis device. Pediatr Critical Care 2023; 24: 604-613. Lambert et al.
Protocol for a multicentre prospective exploratory mixed-methods study investigating the modifiable psychosocial variables influencing access to and outcomes after kidney transplantation in children and young people in the UK. Kim JS et al. BMJ Open 2024; 14(5): e078150.
UK national study of barriers to renal transplantation in children. Kim JS, Marks SD, BAPN et al. Arch Dis Child 2021; 106(4): 384 - 386.
Got a question? Get in touch.
For more information and to find out about getting involved as a patient or researcher, contact: