Autosomal Dominant Polycystic Kidney Disease Clinical Study Group
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease worldwide. It is a chronic, progressive condition characterised by the development and growth of cysts in the kidneys and other organs, notably in the liver in most patients and, less commonly in the seminal vesicles, pancreas, arachnoid membrane and spinal meninges.
ADPKD patients have a higher risk of cardiovascular and cerebrovascular complications, including hypertension, cardiac valvular abnormalities and intracranial aneurysms. Two in three ADPKD patients will experience pain - both acute and chronic - in their lifetime. Pain relief is often inadequate. Kidney and liver cystic complications such as ruptures and infections are frequent and may need surgical intervention if antibiotics are not effective.
Most ADPKD patients develop end-stage renal disease (ESRD), usually before the age of 60 years. ADPKD accounts for approximately one in ten of patients requiring renal replacement therapy (RRT) by kidney transplantation or dialysis. (Data: Renal Registry 31.12.2015). Some patients will require nephrectomies before or after transplant, owing to size and cyst burden. Approximately 40* patients a year will require liver transplants owing to massive bulk, pain and severely impaired quality of life (QoL). Lifelong physical and psychological effects of ADPKD can harm overall QoL and affect the ability to work and function socially.
Until recently, ADPKD was considered a disease of adulthood owing to the late onset of most symptoms. However, studies of children diagnosed with ADPKD reveal that one in three has hypertension.
* NHSBT data for 2018 shows 23 liver transplants for polycystic liver disease although numbers are expected to rise due to new allocation policy for deceased liver donation.
Who we are
We are a multidisciplinary group dedicated to stimulating and nurturing clinical research into ADPKD in paediatric and adult populations.
In addition to nephrology, experts from genetics and transplantation are represented on our group. ADPKD also affects the liver (polycystic liver disease) and we seek to promote research in tackling the effects of liver as well as kidney cysts. There are four patient representative members on the CSG.
The group is chaired by Dr Roslyn Simms who is an Honorary Senior Lecturer in Nephrology at the University of Sheffield and Consultant Nephrologist at the Northern General Hospital.
The CSG is a RaDaR Rare Disease Group.
Currently focusing on known priorities for research, such as hypertension in children, pain relief and improved understanding of natural history and progression (using data collected on RaDaR).
In future years, research will be guided by the outputs of the ADPKD Priority Setting Partnership (PSP) being conducted in 2019 by the PKD Charity in association with the James Lind Alliance.
Evidence gaps and key challenges:
- Agreement on clinical trial endpoints satisfactory to regulators such as FDA and EMA
- Biomarkers in early ADPKD
- Benefits of dietary/lifestyle treatments
- Genetic influences on progression
- Therapies to slow down kidney and liver cyst formation and growth
- Pain interventions
- Infection – triage and treatment
- Incomplete registry data
- Global SONG-PKD initiative – determining core outcome sets for ADPKD. Publication expected Summer 2020
- PKDOC. Polycystic Kidney Disease Outcomes Consortium - collaborative partnership whose research leads to discovery of treatments for PKD
- Participation in European Reference Networks for Kidney (ERKNet) and Liver (Rare Liver ERN)
- ADPedKD. International, longitudinal registry including ADPKD patients followed up from childhood.
Recently completed projects:
- Pilot study of blood pressure in children and young people at GOSH/Evelina. Funded by PKD Charity. Complete (47 children) and submitted for publication.
- DRINK – a feasibility study looking at high vs. ad libitum water intake in ADPKD. Multiple funders. Complete (42 patients) and presented at UKKW 2018 and Kidney Week ASN 2018. Manuscript in preparation.
- ANCHOR (ADPKD Nested Cohort) - a prospective study to populate an ADPKD nested cohort within RaDaR using UK Renal Registry (UKRR) and UK Renal Data Collaboration (UKRDC) systems and data capture. Target 1,200-1,500 ADPKD patients at five renal units registered on the ADPKD RaDaR Registry. Funded by Otsuka UK and facilitated by Kidney Research UK.
- Biomarker study on ADPKD patients attending clinics at UCL Centre for Nephrology Royal Free. Funded by PKD Charity. 350 patients recruited. Presented at UKKW 2018.
- Enrichment of the ADPKD (and ARPKD) paediatric data collected on RaDaR from ten paediatric centres. Funded by PKD Charity.
Studies in development:
- EASE-PKD - Evaluating chronic pain in autosomal dominant PKD using a patient-centred approach to data collection and synthesis: A national prospective observational study. Submitted to NIHR Research for Patient Benefit funding programme.
- Family study of early hypertension in children and young people at risk of autosomal dominant polycystic kidney disease. Submitted to Kidney Research UK.
- QOL study of ADPKD patients with polycystic liver disease (using RaDaR).
- Study to validate point-of-care capillary (finger prick) creatinine testing compared with standard laboratory venous serum creatinine, together with a qualitative assessment of patient experience.
- Clinical Practice Guideline: Monitoring children and young people with, or at risk of developing Autosomal Dominant Polycystic Kidney Disease (ADPKD).
- Inverting the patient involvement paradigm: defining patient led research. Laura B. Mader, Tess Harris, Sabine Kläger, Ian B. Wilkinson, Thomas F. Hiemstra. Research Involvement and Engagement, 2018, Volume 4, Number 1, Page 1. BioMed Central (BMC) July 2018.
- Is it ethical to test apparently “healthy” children for Autosomal Dominant Polycystic Kidney Disease and risk medicalizing thousands? Tess Harris. Front Pediatr. 2017; 5: 291.Published online January 2018.
- Addressing the need for clinical trial end points in Autosomal Dominant Polycystic Kidney Disease: A report from the Polycystic Kidney Disease Outcomes Consortium (PKDOC). Am J Kidney Dis. 2019 Apr;73(4):533-541. doi: 10.1053/j.ajkd.2018.11.001. Epub 2018 Dec 29
For more information and to find out about getting involved as a patient or researcher, contact: