NIHRDataInsights/HRCSData huggingface dataset:
Title: Characterising body fluid distributions and dynamics in the haemodialysis population to develop improved, bioimpedance guided fluid management strategies.
Funder: Department of Health (England)

Abstract: Cardiovascular disease is the leading cause of death of dialysis patients and poor fluid management is associated with the increased risk. `Wrist-to-ankle' bioimpedance measurements can be used to quantify a patient's hydration state and has been shown to improve fluid management. However, there are no recommendations on its use in abnormal patients (e.g. amputees, patients with localised oedema). Hydration status using alternative measurement configurations will be obtained for normal subjects and dialysis patients. Changes with fluid removal during dialysis will be evaluated. The knowledge will be used to develop bioimpedance guided strategies to optimise fluid management across the dialysis population.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: RENAL AND UROGENITAL
Title: Using markers of kidney damage to detect acute disease: understanding normal (biological) variation to realise patient benefits
Funder: Department of Health (England)

Abstract: Background Current diagnosis of acute kidney injury (AKI) using serum creatinine is unsatisfactory. There is intense interest in the use of alternative biomarkers to aid in the early identification of AKI, emphasised in the recent National Confidential Enquiry into Patient Outcome and Death (NCEPOD) AKI report and the Renal National Service Framework (NSF). The last several years has seen the emergence and evaluation of promising novel biomarkers including neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), in addition to other more established markers of injury (N-acetyl-?-D-glucosamindase [NAG], ?1-microglobulin [A1M], cystatin C). An understanding of normal biological variation of markers is essential to interpretation of changes in response to disease. Aims Biological variation data should be generated early in the evolution of new diagnostic and monitoring tests. We will establish the biological variation of NGAL, KIM-1, NAG, A1M and cystatin C amongst people with chronic kidney disease (CKD). This will enable objective selection and use of these markers as tools for the detection of AKI. The following questions will be answered; (i) how much do biomarker measurements need to differ by to truly represent a change, (ii) how many measurements of each biomarker are required to establish an individual’s homeostatic set-point, (iii) are results best expressed as a concentration or as a ratio to urinary creatinine, (iv) does variability differ amongst different groups of CKD patients and (v) are reference ranges appropriate decision tools? Plan of Investigation Patients with stage 1 and 2 CKD (n=20) and three patient groups (each n=20) with stage 3 and 4 CKD ((i) non-proteinuric non-diabetic, (ii) proteinuric non-diabetic and (iii) proteinuric diabetic) will each provide a random urine sample and a blood sample weekly for 6 consecutive weeks. For each patient, each week, blood and urinary biomarker concentrations will be measured. The total (CVT), analytical (CVA), group (CVG) and within-individual (CVI) components of variation will be calculated using nested ANOVA. The critical difference for significant (p Potential Impact It is anticipated that one or more of the biomarkers being evaluated in this study will be in widespread use within the NHS in the next few years. It is likely that they will enable implementation of different and objective patient pathways in the same way that B-type natriuretic peptide and cardiac troponin testing have influenced practice in cardiology. The information obtained from the proposed study will provide a rationale for choice of biomarkers to be used when implementing kidney injury detection strategies and allow clinical decisions in relation to disease management to be made on a scientific basis. CKD patients are being studied since they are at increased risk of AKI.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RENAL AND UROGENITAL
Title: A validated competitive risk model that will inform a decision aid for peritoneal dialysis patients deciding whether to switch modality to avoid developing encapsulating peritoneal sclerosis
Funder: Department of Health (England)

Abstract: Background Peritoneal dialysis, an effective treatment for advanced renal failure is chosen by patients primarily because it best supports their lifestyle. Some patients choosing this treatment develop an unpleasant and life threatening complication termed encapsulating peritoneal sclerosis (EPS). The risk of its development increases in absolute terms with time on treatment (5 year incidence 1-3% of patients, 10 year incidence 20-25% of patients) and changes in relative terms to other possible outcomes (e.g. death or switching to haemodialysis for another reason) according to both patient and treatment characteristics. It is currently difficult for patients and their advising clinicians to know whether they should stop peritoneal dialysis to avoid this complication. Aims To provide the evidence upon which a subsequent risk comparison measure can be developed and encoorporated into a future Patient Decision Aid for use by patients and their clinical teams to facilitate their decision as to whether they should continue on peritoneal dialysis treatment or switch to haemodialysis for the sole purpose of avoiding EPS. The risk measure will take into account the duration of peritoneal dialysis treatment and patient specific factors such as age, primary diagnosis of renal failure, comorbidity and exposure of the peritoneal membrane to glucose. It will indicate the relative chance of developing EPS by staying on PD over the next 12-24 months compared to that of having to stop PD for other reasons (death and technique failure). Plan of Investigation In stage 1 we will bring together world-wide experience from established cohort studies in which there is reliable denominator data and construct a series of 3 risk scores ranging from the very simple (age, primary diagnosis) to more complex (including comorbidity and glucose exposure), that can be applied to patients who have been on peritoneal dialysis for 5 years. In Stage 2 we will validate these risk scores using data from a different cohort covering around 3000 prevalent peritoneal dialysis patients recruited across the UK by expanding the established UK EPS cohort study. Potential Impact This study will provide critical evidence to underpin a Patient Decision Aid we are currently developing to improve renal patient’s choice of dialysis modality. We anticipate that this will mean that some patients/clinicians will be reassured sufficiently to enable peritoneal dialysis to be continued whereas others, often resistant to transfer will be willing to change treatment and avoid this severe complication. Both of these outcomes will have a favourable cost impact in addition to enabling patients to pursue their treatment of their choice while limiting the likelihood of experiencing the morbidity and mortality associated with EPS.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: RENAL AND UROGENITAL
Title: Transplant ureteric stent removal: Early versus standard removal. A Randomised controlled trial.
Funder: Department of Health (England)

Abstract: Background Kidney transplant is the optimum treatment for renal failure. Recognised technical complications of transplant surgery include major urological complications of ureteric leaks and stenosis. Routine use of a transplant ureteric stent (TUS) has been shown to reduce these complications. However stent complications occur in around 20% of patients. Studies suggest that TUS complications are related to the time stents remain in-situ. At our institute stent removal is performed with flexible cystoscopy at 6 weeks, but the optimum timing for stent removal is currently not known. An alternate technique of suturing the TUS to the urethral catheter at the time of transplant surgery would allow earlier stent removal without recourse to cystoscopy or anaesthesia and potentially reduce complications. Aims We aim to determine whether, in comparison to the current practice of cystoscopy & stent removal at 6 weeks, the sutured TUS technique with non-invasive and earlier removal of stent will result in: • A decrease in stent related complications (specifically urinary tract infection, pain and stent migration) compared with current practice stent removal • No increase in ureteric complication rates of ureteric leak or stenosis • Better patient acceptability • A reduction in costs Plan of Investigation The study is a randomised control trial in which there are two potential study arms to which patients will be randomly allocated: GROUP 1 - Current cystoscopic technique for TUS removal (cTUSr) at week 6. GROUP 2 - Sutured technique with early TUS removal (eTUSr) on day 5. eTUSr will be on day 5 as it is the universally accepted day for catheter removal after kidney transplant surgery to minimise infection risks. Data will be collected regarding stent related complications, ureteric complications, costs/healthcare use and patient quality of life assessments for up to 6 months post transplantation on all participants. Potential Impact This study has the potential to change clinical practice for removal of TUS resulting in: A non- invasive procedure for TUSr Removal of the need for cystoscopy and anaesthetic for TUSr Reduction in TUS related complications - particularly urinary tract infections Better Patient acceptibiliy Reduction in costs (procedural, management of TUS complications, hospital admissions) Allow us to define optimal timing for TUS removal


Research activity codes: 6.4 SURGERY
Health categories: RENAL AND UROGENITAL
Title: Exploring the role of Chinese herbal medicine in the treatment of recurrent urinary tract infections
Funder: Department of Health (England)

Abstract: Recurrent urinary tract infections (RUTIs) are a common condition in primary care. Once conventional antibiotic treatment is stopped infections commonly reoccur. There is some evidence that Chinese herbal medicine (CHM) may be able to help prevent and treat RUTIs. A 5-year NIHR Fellowship has been granted to investigate this by:1. Using qualitative research to explore the experience and attitudes of GP’s and patients to managing RUTIs and towards CHM.2. Defining best CHM practice for RUTIs 3. Conducting a clinical trial to assess the impact of CHM in reducing the duration, severity, and incidence of RUTIs.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;6.8 COMPLEMENTARY
Health categories: RENAL AND UROGENITAL
Title: Clinical impact of adopting a new equation utilising cystatin C and creatinine to estimate glomerular filtration rate for diagnosing and risk prediction in older people with chronic kidney disease in primary care
Funder: The Dunhill Medical Trust

Abstract: Chronic kidney disease (CKD) is commonly diagnosed using estimated glomerular filtration rate (eGFR) derived from serum creatinine. Creatinine levels are influenced by muscle mass or diet and may underestimate GFR resulting in overdiagnosis, particularly in older people who have the highest prevalence of CKD. Cystatin-C, another marker of GFR, is no more accurate than creatinine alone, but a recent study has shown them to be more accurate in combination. This has not yet been assessed in routine practice. We aim to evaluate the impact of the combined equation in a group of 1741 predominantly elderly people (mean age 73±9 years) with CKD stage 3 already enrolled in a 10-year observational study. We will compare the prevalence of CKD based on creatinine, cystatin-C or both and the ability of each to predict complications over 5 years. The added cost of cystatin-C will be evaluated against the benefits of reduced CKD overdiagnosis


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RENAL AND UROGENITAL
Title: Welsh Study of Mothers and Babies: Prospective electronic cohort study of renal disease in early childhood
Funder: Division for Social Care and Health Research (Wales)

Abstract: Long term kidney disease is one of the most common illnesses of childhood causing lifelong health needs. Babies born with abnormalities in the kidney are at risk of long-term kidney disease that may require treatment such as dialysis and kidney transplant as they grow older. Opportunities for early diagnosis and treatment of kidney disease may reduce the severity of illness over time. In some pregnancies, a marker (enlargement of the tubes that collect urine in the kidney, called pelvicalyceal dilatation) is detected in the baby’s kidney at the antenatal ultrasound scan. The meaning of this marker for the future health of the baby (for example the risk of urine infections or hospital admissions for kidney problems) is not known. There are no consistent guidelines about how to treat babies with this condition and so the identification of this marker can lead to anxiety for families and additional tests during pregnancy and after birth. We were funded by NISCHR to study the meaning of markers of uncertain significance (Welsh Study of Mothers and Babies). The study has recruited 21,106 pregnant women, with consent to follow-up the babies in future studies. There are 150 babies in our study with the kidney marker. We did not find any associations with immediate birth outcomes such as stillbirth, premature birth or genetic problems We propose to use routinely collected health data to explore whether babies with a marker in one or both kidney(s) detected during pregnancy have more urinary tract infections or hospital admissions for kidney problems during childhood, compared to babies without a marker. This information is vital for pregnant women, families and clinicians to facilitate the development of appropriate clinical guidelines and care pathways during pregnancy and after birth, including the appropriate use of medical interventions and treatment.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: RENAL AND UROGENITAL
Title: Agents for adhesion prevention after gynaecological surgery
Funder: Department of Health (England)

Abstract: Adhesions are the commonest complication of gynaecological surgery with an incidence of 50-100% (DiZerega 2004). Surgical treatment for adhesions is often ineffective and many women suffer with the consequences including: subfertility chronic pelvic pain and bowel obstruction all of which greatly decrease a woman’s quality of life. It is estimated that 5% of women require readmission following gynaecological surgery as a direct result of adhesions one-third of who are re-admitted a mean 2.1 times (Lower 2000). The cost of adhesion-related complications was calculated to be $1.33 billion in the USA in 1994 and is believed to have since dramatically increased (Ray 1998). Thus adhesions have substantial clinical financial and public health implications. A variety of anti-adhesion agents are available but with no clear scientific guidance. Currently agents are used as per availability. This review will update and combine two previous Cochrane reviews one which evaluated fluid agents (Metwally 2006 CD001298) and another which examined mechanical barrier agents (Ahmad 2008 CD000475). This will necessitate a complex network meta-analysis but will produce the first review of all anti-adhesion agents. Approximately 30 studies will be analysed. Conclusions from this review will enable evidence-based practice applicable to both the UK and worldwide.


Research activity codes: 6.3 MEDICAL DEVICES;6.1 PHARMACEUTICALS
Health categories: RENAL AND UROGENITAL
Title: Distal renal tubular acid-base homeostasis in health and disease.
Funder: Wellcome Trust

Abstract: The kidney is vitally important in maintaining steady levels of acid and bicarbonate in bodily fluids and cells, which are necessary not only for normal cellular function throughout the body, but also to prevent the formation of kidney stones and bone thinning, and to allow normal hearing. We have investigated patients who have inherited conditions affecting acid balance, and discovered which genes are abnormal. Using this information, we have started to investigate these genes, the proteins t hat they make and the cells where they are found within the kidney, in order to understand the normal function that has been lost. The programme of research proposed here extends these studies, using a combination of genetics, cell studies in the culture dish , protein studies, and animal models, together with studies designed to help patients. Our ultimate aims are to understand how normal physiology works and eventually to develop new preventive treatments for conditions such as kidney ston es.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RENAL AND UROGENITAL
Title: Are interactions between glomerular podocytes and extracellular matrix compromised in proteinuric kidney disease?
Funder: Wellcome Trust

Abstract: The kidneys are responsible for removing waste products from the blood and for keeping protein molecules in the circulation. Ordinarily very little protein is lost from the kidneys into the urine and proteinuria is an early sign of kidney disease. There are an increasing number of people worldwide with proteinuric kidney disease, however, there are limited treatment options and many endure a relentless progression to kidney failure. In the kidney there are specialised cells called podocytes and research has shown that these cells are very important in proteinuric kidney disease. Podocytes need to attach to surrounding tissue, however we do not understand how this process is controlled. This research will examine podocyte attachment proteins by isolating protein complexes and analysing them with a new approach. This will involve breaking up the protein building blocks and sophisticated computer software will then create maps of protein interactions. The central aim of this project is to define the protein connections which are required to establish and maintain normal podocyte function and to consider how these connections are disrupted in disease. This could lead to the development of targeted treatment in early proteinuric kidney disease and could prevent progression to kidney failure.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RENAL AND UROGENITAL
Title: A Portable, Low Cost, Electronic Urine Flow Meter to Assess Lower Urinary Tract Symptoms (LUTS).
Funder: Wellcome Trust

Abstract: Many older men suffer unpleasant urinary symptoms, such as weak stream and waking at night to urinate, caused by enlargement of the prostate. If untreated, symptoms generally worsen and can lead to infection, incontinence or the total inability to urinate. Currently, in order to assess these symptoms, a single measurement of urine flow is made in the hospital clinic. This has the disadvantage of giving only a single, potentially inaccurate reading, whilst having to 'perform on order' can be difficult for the patient. To try and measure how the problem affects his life, the patient is asked to manually record a 'voiding diary' by noting the time, date and volume of each urination for up to one week. We have invented a highly portable, electronic urine flow meter designed for ease of use in the patient's home, without embarrassment. It is inexpensive and potentially disposable after use by one patient. It will record multiple urinations, providing more detailed and accurate readings compared to a clinic flow test. This project aims to refine the prototype device; making it user-friendly and suitable for mass manufacture. We will then establish whether it is better than current methods by carrying out a patient trial.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: RENAL AND UROGENITAL
Title: Analysis of conserved pathways involved in maintaining homeostasis and survival in mammals and Drosophila.
Funder: Wellcome Trust

Abstract: Our health depends on the removal of waste products, that build up as we breathe and exercise, and also on the expulsion of toxins that we ingest from the environment. There is still much to be discovered at the molecular level about how this is done. We focus on two systems that perform these functions; the kidney, in which cells called podocytes filter waste and toxins into the urine for excretion, and a population of scavenging cells, which ingest and remove toxins from body fluids. We have i dentified a simple model for the filtration and scavenging of body fluid toxins in the fly; a group of cells called nephrocytes. Further, we have shown that nephrocytes use the same molecular pathways as vertebrate podocytes and scavenging cells for these functions. We plan to use genetic techniques available in the fly to identify all the molecules active in these pathways, to find out how they function in the fly and then test their activity in vertebrate podocytes. As defects in these pathwa ys are known to cause human disease, including kidney failure and cancer, our work will uncover the basis of disease and identify future therapies.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: RENAL AND UROGENITAL
Title: Planar cell polarity in glomerular development and disease
Funder: Wellcome Trust

Abstract: During kidney development, podocytes acquire a highly branched morphology essential for their function in glomerular filtration. Loss of this morphology leads to proteinuria and underlies many kidney diseases. Development and maintenance of podocyte architecture involves cytoskeletal reorganisation, but little is known about the pathways regulating this process. One potential candidate is the planar cell polarity (PCP) pathway which regulates cytoskeletal organisation and cell shape in a variety of cell types. I have previously shown that a mutation in Vangl2, a core PCP component, is required for branching morphogenesis at the start of kidney development and that podocytes express several PCP genes as they differentiate, both in-vivo and in-vitro. The aim of this fellowship is to determine the role of the PCP pathway in the development and maintenance of podocyte morphology in health and disease. Using transgenic mouse technology, I will examine the effect of conditional deletion of Vangl2, a core PCP gene, on podocyte morphogenesis during development, in the mature kidney and in animal models of glomerular disease. Finally, I will determine changes in Vangl2 and other PCP molecules in human glomerular disease.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RENAL AND UROGENITAL