NIHRDataInsights/HRCSData huggingface dataset:
Title: Frailty - why does it matter in kidney transplantation?
Funder: Public Health Agency, NI

Abstract: Frailty is a clinical syndrome that develops because of decline in multiple systems with associated decreased physiological reserve and ability to respond to stressor events. It is associated with greater healthcare burden. It is common in patients with end-stage kidney disease (ESKD). Kidney transplantation (KT) is the optimal treatment for ESKD; however, surgery and immunosuppression are physiological stresses that can disproportionately affect frail individuals. The 2020 KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation has recommended that frailty assessment is part of candidate evaluation. In European KT populations, the prevalence of frailty and its impact on transplant outcomes are unknown. Aims: 1. To assess how KT modifies recipient frailty; 2. To determine how frailty at time of KT impacts transplant outcomes; 3. To determine the most clinically appropriate method of frailty assessment in KT candidates. Methods: All waitlisted kidney transplant candidates will be recruited from August 2022 to August 2024 (n=240). Frailty assessments of all recipients will be carried out pre-operatively, at time of transplantation, 1-month, 3-months and 1-year post transplant. The primary frailty assessment will consist of the Fried Phenotype. Secondary frailty assessments will include the Short Physical Performance Battery, Clinical Frailty Scale, Edmonton Frail Scale and the FRAIL scale. Participants who are waitlisted but not transplanted will have repeat frailty assessments at 1-year post listing. Outcomes: Primary outcome will be change in frailty score at 3-months. Secondary outcomes will include re-hospitalization, length-of-stay after transplant, cumulative inpatient days within the first 6-months post-transplant, delayed graft function, immunosuppression intolerance, graft survival, recipient survival and change in frailty. When assessing outcomes, regression modelling will be used to adjust for established confounders.


Research activity codes: 6.4 SURGERY
Health categories: RENAL AND UROGENITAL
Title: A mixed methods project exploring the use and risks associated with overactive bladder (OAB) medication in adult women in Northern Ireland
Funder: Public Health Agency, NI

Abstract: Background - Overactive bladder syndrome (OAB) is a symptom complex characterised by urinary urgency, frequency and nocturia. It is a common problem in the adult population, with prevalence in women ranging from 9-39%. The incidence of OAB increases with age and is more commonly reported in women. A class of medication used to treat OAB targets primarily muscarinic receptors in the bladder. In 2020, 606,148 prescriptions for genitourinary drugs were issued at a cost of £7.4 million which includes OAB medication. These medications have anticholinergic (ACh) properties and concerns have been raised about the potential impact of ACh medications on cognitive function, risk of dementia, vascular disease (defined as Ischaemic heart Disease, Cerebrovascular Disease and Transient Ischaemic attacks) and mortality. This correlation has prompted healthcare professionals to focus on reducing ACh medication prescribing. Aims - To address a clear gap in literature relating to OAB Ach medication and associated risks. Methods - This project will utilise different methodologies with seven objectives: (1) a systematic review and meta-analysis of current literature on OAB medication and associated health risks. Objectives (2)-(5) will be a longitudinal data-linkage using the Enhanced Prescribing Database, Patient Administration Service and General Registrar’s Office to explore the prevalence of OAB Ach medication use, associated risks posed by this class of medications, evaluation of previous Ach burden scales used to measure overall medication burden and importantly if on cessation of OAB medication are the effects reversible? Objective (6) Focus groups will be used to get a deeper understanding of women`s experience of living with OAB and their attitudes to health risks and deprescribing. Objective (7) The findings will be used to develop patient and clinical aids to facilitate communication of health risks associated with OAB medication and integration of Ach scoring into electronic healthcare records.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: RENAL AND UROGENITAL
Title: CHAPS - Clinical and Histological Assessment of Predictors of Disease Severity in Balanitis Xerotica Obliterans (Lichen Sclerosus et atrophicus of the male genitalia): a prospective observational study).
Funder: The Urology Foundation

Abstract: A grading system for paediatric BXO that reflected disease severity and accurately predicted cases of BXO that are more likely to relapse after intervention, would allow clinicians to identify high-risk patients and plan treatments accordingly. It would also provide a standardized means to classify BXO for future research, facilitating comparison and improving reproducibility.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: RENAL AND UROGENITAL
Title: The development and feasibility trial of a complex intervention to improve AccesS to living-donor Kidney transplantation: the ASK trial
Funder: Wellcome Trust

Abstract: The UK’s living-donor kidney transplant (LDKT) activity falls behind many other countries internationally with less than 20% of those eligible receiving a LDKT each year. Certain individuals with renal disease in the UK appear to be particularly disadvantaged in accessing a LDKT: the most socioeconomically deprived people with kidney disease are 60% less likely to receive a LDKT than the least deprived. This mixed-methods programme of research incorporates three phases: 1. Intervention development 2. Feasibility trial with process evaluation 3. Randomised Controlled Trial (RCT) with internal pilot The aim of Phase 1 will be to develop a multicomponent complex intervention that increases the proportion of eligible kidney patients that receive a LDKT by supporting individuals, particularly those currently disadvantaged, to overcome barriers to accessing such a transplant. LDKT interventions in use in the Netherlands, the USA and Canada will be combined and adapted for use in the UK. Phase 2 will establish the feasibility of delivering the developed intervention in existing NHS care pathways by diverse practitioners at different hospital sites, and the feasibility of running a trial of the developed intervention. Findings will be used to decide on progression to and design of Phase 3 (proposed Stage 2 fellowship).

Lay abstract: A living-donor kidney transplant (LDKT) is the best treatment in terms of life-expectancy for most people with kidney failure. The UK’s LDKT activity falls behind many other countries. Certain individuals with renal disease in the UK are disadvantaged in accessing a LDKT: the most socioeconomically deprived people with kidney disease are 60% less likely to receive a LDKT than the least deprived. This research incorporates three phases: Intervention development Feasibility trial with process evaluation Randomised Controlled Trial (RCT) with internal pilot I will develop a multicomponent intervention, combining approaches in use outside the UK, to help individuals to overcome identified barriers to accessing a LDKT. I will establish the feasibility of delivering and evaluating the intervention in existing NHS care pathways by diverse practitioners at different hospitals. If feasible, I will then undertake Phase 3 (Stage 2 fellowship) to determine the effectiveness of the intervention at increasing uptake of LDKTs.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: RENAL AND UROGENITAL
Title: Defining Causal Variants and Associated Genes in Polygenic Nephrolithiasis
Funder: Wellcome Trust

Abstract: Kidney stones, which are a major clinical and economic health burden, are commonly recurrent, and current stone prevention strategies are relatively ineffective. The renal tubular mechanisms underlying this disease are poorly understood, thereby limiting opportunities to develop novel therapies. Via a genome-wide association study (GWAS) we identified twenty genetic loci linked to kidney stone formation. However, the genes influenced by these loci remain to be elucidated. My goals are to: identify additional stone-associated loci by X chromosome and sex-specific GWAS studies; define biologically relevant renal cell types by identifying areas of accessible chromatin at relevant loci through single cell assays for transposase accessible chromatin (ATAC)-sequencing in renal tissue; determine causal GWAS-associated SNPs by examining local epigenetic modifications in relevant cell types via chromatin immunoprecipitation (ChIP)-sequencing; link causal SNPs to effector genes by determining the 3-dimensional chromatin landscape in relevant cell types through Next Generation Chromatin Conformation Capture; validate predicted genotype-phenotype associations in relevant cohorts; and elucidate the roles of effector genes in cellular function via in vitro studies. This research will provide new insights into tubular function and the molecular pathophysiology of renal stone disease and reveal new therapeutic targets for the prevention of kidney stone recurrence.

Lay abstract: Kidney stones are a common problem. Unfortunately, the causes of kidney stone formation are poorly understood, stones are frequently recurrent, and prevention strategies are relatively ineffective. I have identified 20 areas on the genome (loci) that are linked to stone formation but it is not known what effects variations in DNA sequence at these loci are having on how genes are converted to proteins and on biological pathways. The aim of my project is to link these loci of interest to cellular function. I will do this by looking at the structure of DNA in different kidney cell types, using laboratory-based techniques to identify what effects genes of interest have on biological pathways, and studying how variations in DNA sequence associate with biological characteristics in people. These studies will help us understand the causes of kidney stone formation and identify targets for novel preventative drug therapies.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RENAL AND UROGENITAL
Title: Assessing the impact of genetic variation on chronic kidney disease in Africa
Funder: Wellcome Trust

Abstract: In sub-Saharan Africa, over 50 million people have chronic kidney disease (CKD) making Africa the continent with the highest burden of CKD in the world. With rapidly increasing urbanisation, trends towards unhealthy diets, obesity and increases in metabolic risk factors, the projected increase in the prevalence of CKD may be even greater in Africa than in other parts of the world. Over the past decade, genome-wide association studies have uncovered numerous genetic determinants of CKD in European and Asian ancestry populations. These studies have led to numerous novel findings, which are helping improve our understanding of factors and pathways affecting both normal and pathologic kidney function. However, to date, there is no known published GWAS of CKD in any continental African population. Key goals include 1. Conduct large-scale genomic studies of CKD in Africa which will potentially provide new opportunities to identify the biological determinants of CKD in individuals of African ancestry. 2. Leverage the low linkage disequilibrium between genetic markers in African populations to conduct fine-mapping of novel and previously identified signals in the trans-ethnic meta-analysis. 3. Develop a Polygenic Risk Score for CKD risk in Africa and assess whether cardiometabolic traits/diseases are causally related to the risk of CKD in Africans.

Lay abstract: CKDs are the most common form of kidney diseases, with an estimated prevalence around the world of about 10.4%. Between 5.3 and 10.5 million people require dialysis or transplantation, though there are many who die because they do not receive these treatments due to lack of resources. In Africa alone, more than 50 million people have CKD, making Africa the continent with the highest burden of CKD in the world. With rapidly increasing urbanisation, trends towards unhealthy diets and obesity, the projected increase in the prevalence of CKD may be even greater in Africa. CKD is costly for African populations and poses a threat to economic development due to the high medical care costs associated with it. The proposed study seeks to identify and understand the genetic variations that contribute to CKD. We anticipate that our findings will yield insights that will guide the prevention and treatment of CKD.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RENAL AND UROGENITAL
Title: Investigating the phenotype, cellular interactions, and function of kidney-resident natural killer cells in health and chronic kidney disease
Funder: Wellcome Trust

Abstract: Kidneys play a vital role in homeostasis. Chronic kidney disease (CKD) is characterised by kidney dysfunction and organ fibrosis, and affects millions of patients worldwide, but the underlying pathogenic mechanisms are poorly understood. Using single cell RNA sequencing, we have shown that the human kidney contains a network of tissue-resident immune cells, including macrophages and two subsets of natural killer (NK) cells. These NK subsets have distinct transcriptional signatures suggestive of differing interactions with macrophage subsets, and the potential to variably influence tissue repair/fibrosis by via production of the epidermal growth factor receptor ligand amphiregulin (AREG) and by regulating macrophage polarisation towards a wound-healing M2 phenotype. My key goals are: 1. To determine the functional characteristics, cellular interactions, developmental relationships and lifespan of NK cell subsets in normal human kidney. 2. To understand how the global kidney immune landscape and NK cell phenotype/function/interactions change in CKD. 3. To determine if NK-cell depletion or NK cell-specific AREG-deficiency affects macrophage polarisation and kidney fibrosis in mouse models of kidney injury. Answering these questions will provide critical information about tissue immunity in the kidney, delineate previously unappreciated aspects of NK cell biology, and will potentially identify new therapeutic targets for CKD.

Lay abstract: Background The kidneys clean the blood but can be scarred by infection, high blood pressure and inflammation, leading to 'chronic kidney disease' (CKD), a problem that affects hundreds of millions of people worldwide. We have recently found that different types of immune cells, the body’s defence cells, live in the kidney. We want to understand if one type, ‘NK cells’ contribute to tissue scarring in CKD. Approach We will use samples from normal human kidneys and kidneys with CKD. We will study the genetic code and exact position of NK cells to determine where and how long they live, whether they accumulate in CKD kidneys, and if they produce chemical messengers that cause scarring. We will also use mouse models of CKD to find out if taking away NK cells or their chemical messengers reduces scarring. Impact This work will potentially allow us to identify new ways of treating/preventing CKD.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RENAL AND UROGENITAL
Title: Amber-UI: A closed-loop bioelectronic system for urinary incontinence
Funder: Innovate UK

Abstract: Urinary incontinence (UI) is a common condition that can severely impact physical, mental and financial wellbeing. Though it is thought at least 8.5% of the global population suffer from UI, many do not admit it, with fewer than half of adults with severe UI seeking help from healthcare providers; one study found that men would rather admit to sexual impotence than symptoms of incontinence. Amber-UI will be a highly innovative implantable bioelectronic neuroprosthesis intended to provide synthetic continence reflexes in patients with UI who have not responded to simple treatments like lifestyle changes, pelvic floor exercises, medication, bladder injections, etc. Where current options for these patients consist of high-risk, variably successful surgery or dated on-size-fits-all electrical stimulation therapies that mostly only reduce rather than cure symptoms, Amber-UI will bring intelligent adaptive stimulation. It will respond to the individual patient's physiology and measurable biomarkers of both 'urge' (the sudden need to urinate) and 'stress' events (coughing, sneezing, lifting, etc). In effect, Amber-UI will restore the normal mechanisms of continence in a large group of UI patients so that they remain dry all the time---transforming these patients' lives. Conducting experimental medicine in first-time-in-human studies, this project will refine Amber-UI's minimally-invasive surgical technique so that it requires a similar surgeon skill/time commitment as current electrical stimulation therapy surgeries, and it will explore and optimise Amber-UI sensing and stimulation to ultimately provide patients with synthetic reflex control of continence.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: RENAL AND UROGENITAL
Title: Female-specific Urinary Catheter to reduce Catheter-Associated UTIs and improve quality of life
Funder: Innovate UK

Abstract: Ingenion Medical Limited (Ingenion) is a UK medical device SME with a core project team of Edward Cappabianca (project/commercial lead and sustainability/diversity manager), Zia Mursaleen (financial controller), Jeremy Russell (technical lead), Aaron Walsh (technical support) and George Yardy (urologist). Ingenion is solving a significant unmet need with its affordable and reliable urinary catheter designed specifically for the female anatomy that will help reduce infections. With less discomfort and more control over their urination, users of Ingenion's catheter can lead more physically active lives. The solution will also save the NHS money and resources like nursing care and bed-days.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: RENAL AND UROGENITAL
Title: Extending the durability of home-based dialysis
Funder: Innovate UK

Abstract: Home-based dialysis offers considerable benefits to patients, is less expensive than in-centre dialysis, and is much more profitable for dialysis manufacturers. However, serious side effects cause complications which limit treatment durability. Invizius Limited is a Scottish biotechnology company focused on transforming dialysis care with novel solutions that reduce dialysis-induced complications and improve patient outcomes. This project focuses on the development of a solution for home-based dialysis that aims to reduce the therapy's effects and prolong its usefulness. If successful, the product will lead to significant quality of life gains for patients, substantial savings for healthcare payers and economic growth for dialysis equipment manufacturers.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: RENAL AND UROGENITAL
Title: Development and evaluation of a next-generation safety device for haemodialysis and safety-critical vascular lines
Funder: Innovate UK

Abstract: Each year, across the US and EU/UK, 1.3M patients with end-stage renal failure ("ESRF") undergo 202M episodes of haemodialysis. Among them, a staggering 1000 haemodialysis patients die each year from fatal needle dislodgement -- a complication that occurs when forces dislodge the needle from the fistula site. Safety concerns over catastrophic needle dislodgement complications remain the number one barrier to greater patient uptake of home and/or nocturnal dialysis - these emerging modalities improve patient experience and outcomes; and save up to £15,000 per person per year in provider costs. This industrial research SMART project will achieve a technological leap forward in dialysis line safety with potential widespread adjacent application. An integrated connected medical device with the capability to secure and sense dislodgement force on dialysis lines will be developed to a high-fidelity prototype with involvement of clinicians and patients. Support from Innovate UK will secure this project's impact, generating health and economic value for healthcare, UK SMEs, manufacturing and supply chains.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: RENAL AND UROGENITAL
Title: Development of novel models of kidney damage using induced human pluripotent stem cells
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Animal models play a central role in the study of chronic kidney disease (CKD). Researchers have used mice and rats to model kidney damage seen in human patients with diabetes, focal segmental glomerulosclerosis, lupus and fibrosis injury. Although many useful gene and protein targets have emerged from these studies, rodent models are limited for a number of reasons. One is the ethical issues around the numbers of mice in particular that are needed to generate gene knockouts, particularly tissue-specific knockouts (usually in the 100s-1000s). A second limitation is the fact that mice and rat models do not faithfully recapitulate the disease phenotype seen in the human kidney. For example, the most commonly used genetic strain of mice, C57Bl/6, are resistant to diabetes-induced kidney damage. Many gene and proteins that have been identified in rodent models have failed to materialise as bona fide targets when tested in humans. These limitations have led to a growing frustration in academia and industry, and led to the drive to improve our models of CKD.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: RENAL AND UROGENITAL