NIHRDataInsights/HRCSData huggingface dataset:
Title: Proteomic analyses of kidney glomerular extracellular matrix in health and disease
Funder: Kids Kidney Research

Abstract: Many kidney diseases, of different primary causes, cause cells inside of the kidney to form scar tissue, which has some resemblance to incompletely formed muscle. This tissue can lead to further deterioration of kidney function and eventually hasten the need for dialysis and transplantation. We recently discovered that a gene called Teashirt (pronounced “T-shirt”) is essential for normal formation of muscle within the ureter, the tube connecting the kidney with the urinary bladder. We also have found that Teashirt genes are active in the kidney itself. In this project we will follow-up these leads to better define how these genes are working in the kidney, during health (during both maturation and adulthood) and also in disease. In the longer term, insights from this study may help us understand why kidneys fail to work but also suggest new options for treatment.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: RENAL AND UROGENITAL
Title: Comprehensive mutation screening of gene pathways using Next Generation Screening in a national patient cohort with Steroid Resistant Nephrotic Syndrome
Funder: Kids Kidney Research

Abstract: Steroid resistant nephrotic syndrome (SRNS) is a common kidney disease that leads to breakdown of the kidney filter, and frequently to kidney failure. It is now known that at least several dozen different genes could be altered in SRNS and we know almost nothing about how different alterations affect disease severity or response to treatment. This project aims to identify these gene alterations in all UK SRNS children and analyze how these different alterations affect the response of each patient to treatment, by means of carefully collected clinical data. The benefits of this will be to improve standards of patient care, including diagnostics and disease management.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RENAL AND UROGENITAL
Title: Examining the effects of vitamin D receptor activators on vascular smooth muscle cell calcification using a model of intact vessels from children with chronic kidney disease
Funder: Kids Kidney Research

Abstract: Vitamin D is widely used to prevent rickets in chronic kidney disease (CKD) and may protect against cardiovascular disease. However, in some studies it has also been shown to cause calcification or ‘furring up’ of blood vessels, and calcification of the arteries is responsible for the very high mortality in children and adults with CKD. Currently it is unclear how it works. Various forms of vitamin D may have different effects by increasing calcium uptake through channels in the vessel wall, or increasing the activity of genes that directly promote calcification. We have developed a model of intact human vessels, taken at the time of routine surgery, from children undergoing kidney transplants or dialysis catheter insertions. This model has been well validated and is now considered the gold standard for studying calcification in CKD. We will use intact vessels from children with CKD and treat them with the 3 commonly used forms of vitamin D. We will determine how each form of vitamin D works by measuring calcium levels and the genes that regulate calcification in the vessels, by doing detailed microscopy work and blocking or promoting the activity of genes and channels in the vessel wall. This study will help us to find the type of vitamin D medication that causes the least calcification and vessel damage. This will inform future clinical practice on the best type of vitamin D in CKD, which can then be tested in a clinical trial.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: RENAL AND UROGENITAL
Title: Understanding the role of planar cell polarity in the kidney filtration barrier
Funder: Kids Kidney Research

Abstract: The kidney filtration unit known as the glomerulus, is a highly complex structure created from several different cell types. Increasing evidence suggests that one of the cell types that make up the glomerular filter, the podocyte, is crucial for glomerular function and integrity. Podocytes have a highly branched shape acquired as the kidney develops in the embryo; this shape is essential to prevent the leakage of protein and other important blood constituents into the urine. Disruption to this shape, a feature of many childhood and adult kidney diseases such as minimal change disease and diabetic kidney disease, leads to loss of protein in the urine and if persistent to end stage kidney disease requiring life-long dialysis or transplantation. Understanding how podocyte shape develops in the first place, could provide the knowledge necessary to restore it after injury and thus greatly improve treatment of many kidney diseases. In this project, we will study the role of a group of molecules (the planar cell polarity pathway) in the creation of podocyte shape during health and in the repair process after injury. Targeting this pathway in the future has the potential to be a novel therapy for patients with kidney disease.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: RENAL AND UROGENITAL
Title: Establishment and extension of a comprehensive national database of nephrotic syndrome in childhood
Funder: Kids Kidney Research

Abstract: The applicant has recently created a new mutant mouse that develops cystic kidney disease and mimics nephronophthisis. He plans to use kidney cells from these animals to understand how the disease gives rise to kidney cysts and kidney failure and to design drug treatments which reach the cysts and slow down their progression.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RENAL AND UROGENITAL
Title: Levamisole in steroid sensitive nephrotic syndrome; laboratory insights into mechanisms of action
Funder: Kids Kidney Research

Abstract: Oral glucocorticoids are the most commonly used treatment for Nephrotic Syndrome. However these have severe side effects. Levamisole is used in children with steroid sensitive NS as a steroid-sparing agent. How Levamisole works is unclear but there is evidence it works on the podocyte. This project is to understand how Levamisole affects this cell in both health and disease, to help develop new treatments for Nephrotic Syndrome


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: RENAL AND UROGENITAL
Title: Targeting the lymphatics as a therapy for polycystic kidney disease
Funder: Kids Kidney Research

Abstract: Individual centres or clinicians see too few cases of rare diseases to gain the requisite experience for optimal management. This is also a barrier to effective research. RADAR (the rare disease registry) is a significant start to the vision of well-managed and fully inclusive disease registries, developed on a sustainable basis. This project will extend the range of patients collected and allow research, patient information and the advancement of patient management on a genuinely evidence based platform


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: RENAL AND UROGENITAL
Title: Design, development & pre-piloting of PLANT: a mixed method study in the 13 UK childrens kidney units
Funder: Kids Kidney Research

Abstract: Normal kidney structure is destroyed in polycystic kidney disease (PKD) by fluid filled cysts, leading to kidney failure. Only one current treatment for PKD is looking hopeful, called Tolvaptan. It has major side effects and has not been tested in children. The applicant has discovered large changes in the blood and lymphatic vessels in PKD and believes that cysts need these changes in order to grow. To test this theory, they treated PKD mice with a potent regulator of lymphatics called VEGF-C: this significantly reduced the number of cysts, making it an exciting new potential treatment for PKD. They now plan to investigate a more potent lymphatic molecule called VEGF-D and a chemically-modified version of VEGF-C which is believed to be more specific. This exciting area offers novel strategies for future management of PKD aiming to prevent kidney failure from childhood


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: RENAL AND UROGENITAL
Title: Cilia & cystic kidney disease - a new treatment model for nephronnophthisis
Funder: Kids Kidney Research

Abstract: In the 13 UK children’s kidney units, children and young people with CKD stages 3-5 are looked after by groups of professionals (e.g. clinical psychologists, dieticians, doctors, pharmacists, play-workers, nurses, social workers, therapists) known as multidisciplinary teams or MDTs. Research tells us that children grow and develop better and are usually happier at home. Therefore, whenever possible MDTs show parents how to care for their child’s CKD at home. Some professionals also visit families at home to help parents get used to health-care.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: RENAL AND UROGENITAL
Title: Function of Fanconin 3, a new renal disease gene.
Funder: Kids Kidney Research

Abstract: The kidneys are responsible for cleaning our blood by eliminating waste products. To this end, tiny little filters in our kidneys, called glomeruli, first filter our blood. In an adult, approximately 150 litres of blood are filtered this way and obviously, the vast majority of this filtrate must be returned back (“reabsorbed”) into the bloodstream to prevent serious loss of fluid and the solutes contained within. To do so, the glomeruli are attached to tiny little tubes called tubules. Most of this work of reabsorption is performed in the beginning of these tubules, called the “proximal tubule”. In fact, the proximal tubule is the only part of the tubule for the reabsorption of several substances, including small proteins, which are too small to be retained by the glomeruli. This is a key function, as the small proteins are often highly specialised carrier proteins for important substances, such as vitamins. Without reabsorption, these substances would be lost in the urine. The study of some rare diseases that affect this reabsorption pathway, as well as other research have helped us to understand better how this reabsorption works, but we still do not fully know all the details. We now have identified children with a rare and previously unrecognised disease that includes significant losses of these small proteins in the urine. We have identified the causative gene, which we called Fanconin3. Here we propose to study this newly recognised gene, as it will provide important insight into the function of the proximal tubule


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RENAL AND UROGENITAL
Title: Does vinculin regulate force within the glomerular podocyte?
Funder: Kids Kidney Research

Abstract: Each kidney glomerulus is exposed to force due to flow across and stretch of the capillary wall. These forces can increase in kidney disease and this can lead to further decline in kidney function. We think that specialised cells in the glomerulus are able to sense and respond to forces. These cells are known as podocytes and they have unique cell-cell junctions. In this study we will employ in vitro and in vivo techniques to examine barrier function with and without the force regulating protein vinculin. This project addresses an under-investigated question in the field and is very likely to improve understanding of how kidney cells sense and respond to force


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: RENAL AND UROGENITAL
Title: Genetic characterisation of bladder exstrophy and related conditions of the lower urinary tract.
Funder: Kids Kidney Research

Abstract: Bladder exstrophy is a serious condition that affects the development of the lower urinary tract during early pregnancy. There is evidence that this developmental problem is caused by changes in genes. We have used new genetic techniques (genotyping arrays and next generation sequencing) to define the genes responsible for other bladder disorders and now propose to apply these to identify genes responsible for bladder exstrophy. The study will lead to accurate risk estimation of recurrence for parents with an affected child, an understanding of the reasons for this serious health problem and a starting point for the development of personalised treatment


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RENAL AND UROGENITAL
Title: Complement fixing donor specific HLA antibodies in paediatric renal transplant patients.
Funder: Kids Kidney Research

Abstract: Patients can develop proteins called antibodies against a kidney transplant due to immune differences between the donor and recipient. This can lead to rejection and damage with eventual loss of the kidney transplant. In children, some of these antibodies can disappear. Some children are also able to maintain good kidney transplant function despite the presence of these antibodies. It is important to distinguish between the high risk group who progress to losing their transplants and the low risk group, who remain stable. To achieve this goal, we propose to use a novel test for antibodies binding C1q, a component of the complement system which can cause damage to cells. We hope that this will help us identify the high risk group who we can then treat with increased immunosuppression.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: RENAL AND UROGENITAL
Title: A prospective randomised cross-over study to examine feasibility and effect of extended treatment time on markers of nutritional status, cardiovascular disease and inflammation in prevalent haemodialysis patients.
Funder: Department of Health (England)

Abstract: Results from our centre over the last 10 years suggest that patients who had extended haemodialysis treatment time appeared to live longer, but this is not proven. Conventional targets for dialysis dose do not take this fully into account, and there may be scope to improve treatment effect. As poor nutrition and heart disease are the biggest causes of death, we will see if treatment time affects these processes. We will assess change in serum albumin, a marker of malnutrition and mortality, when patients are treated with extended hours and with standard hours over a 12-month period to definitively answer this question.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;6.3 MEDICAL DEVICES
Health categories: RENAL AND UROGENITAL
Title: Further exploring the stories that children and young people tell about their surgery and living with DSD
Funder: Department of Health (England)

Abstract: My clinical development will focus on strengthening my leadership skills and exploring avenues and opportunities for nurse-led service development, new technologies and innovations. My academic development will encompass gaining skills in the supervision of postgraduate research students, developing an understanding of academic governance and the influence this has on health research. I also intend to enhance my portfolio of peer-reviewed publications, build on my academic writing skills, further disseminate my PhD work and strengthen my chances of successful future grant applications. My research project, whilst following on from my doctoral study, will break new ground by exploring and comparing the stories of children and young people who have either chosen to have or not have reconstructive genital surgeries for DSD. I am keen pursue international collaboration with recognised centres of excellence. I further plan to further develop my research skills and knowledge specifically within my methodological area of narrative inquiry.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;6.4 SURGERY
Health categories: RENAL AND UROGENITAL
Title: Post Doctoral Fellowship: Deciding not to dialyse in advanced chronic kidney disease - Health related quality of life, decision making, costs and impact on carers
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: This mixed methods study will examine health related quality of life (QoL), decision making and costs in patients with advanced chronic kidney disease who have opted to receive conservative kidney management rather than dialysis. Patients will be followed 3 monthly over one year or till death. Costs to carers and QoL of life will also be studied. The study will illuminate the interation of clinical care decisions on trajectories of carer-receiving and care-giving. It will inform the decision making process, between patients, carers and staff, and against dialysis, to improve clinical outcomes and carer giver experience.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: RENAL AND UROGENITAL
Title: Data fusion in haemodialysis patients
Funder: Department of Health (England)

Abstract: Patients with kidney failure being treated by haemodialysis frequently experience symptoms similar to fainting during their treatment. This condition is known as intradialytic hypotension (IDH) and not only affects their sense of well being but also reduces life expectancy. IDH often occurs without warning and so the nurses are unable to provide preventative treatment. This project aims to develop sophisticated monitoring techniques capable of predicting episodes of IDH. This will allow timely intervention to prevent its occurrence, reduce the symptoms experienced by the patient and hopefully improve their outcomes. The monitoring approach to be developed uses a computing technique called data fusion to integrate simple measurements from the patient into a score that gives an overview of the risk of IDH; this approach has proven of value in predicting deterioration in other patient groups.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: RENAL AND UROGENITAL
Title: Evaluation of interventions for Overactive Bladder and Detrusor Overactivity: Development and application of evidence synthesis methods for extensive treatment networks
Funder: Department of Health (England)

Abstract: Overactive Bladder (OAB) with Urinary Incontinence affects approximately a third of adults over 40 in the UK. The condition has a severe detrimental effect on all aspects of patients’ quality of life, and use of NHS resources. There are numerous interventions that are recommended for OAB. However, in the existing literature, there has been no comparison between all of the available interventions. This project aims to develop and apply evidence synthesis methods to evaluate the clinical- and cost-effectiveness of interventions for OAB. Consequently, a superior intervention will be identified, or an efficient evaluaton of the treatment contenders will be designed.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: RENAL AND UROGENITAL
Title: CONTINENCE ACROSS CONTINENTS TO UPEND STIGMA AND DEPENDENCY (CACTUS-D)
Funder: Economic and Social Research Council

Abstract: Urinary incontinence (UI) is a common and bothersome condition that affects up to fifty percent of older women living independently in the community. The condition causes sufferers shame and embarrassment which can lead to social isolation and depression. UI is also associated with falls and is a major factor in admission to residential care. Surveys suggest that only 13% to 50% of women with continence problems ever talk to a health care practitioner about their condition, or seek treatment. However UI is largely treatable, with cures and improvements obtainable at all ages, even with conservative management. UI has a huge impact on quality of life for large numbers of older people. Although treatment for incontinence has been shown to benefit older adults, there has been very little work carried out on continence promotion. CACTUS-D builds on previous work in Canada, where two different methods of helping people with continence problems were developed. One was a health promotion workshop that explained the facts about UI, and encouraged women to see their Doctor about the problem. The other, an evidence based self-management tool which presents strategies the women can try themselves to improve their continence, for example losing weight or reducing caffeine intake. Both the workshop and the self management tool have been shown to encourage women to take action to improve their continence and not to accept UI as an inevitable part of ageing. In this project, we want to test both the workshop and the self management tool separately and together and compare them with a control group who are given a general talk about older women's health. These tests will take place in France, UK and two centres in Canada. The project will investigate which is the most effective way of helping older women to improve their continence status. The results of this project should lead to new evidence based continence promotion strategies that can be incorporated into health promotion policies across Europe and beyond.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: RENAL AND UROGENITAL