The Interaction Between Kidney Disease And Cardiovascular Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$44,013.00
Summary
People with chronic kidney disease have increased risk of cardiovascular events and mortality. Establishing predictors of these events can identify individuals most at risk and stratify therapy. Modifying risks reduces the progression of disease in people with chronic kidney disease. Risk prediction modelling has been done, but is not validated and requires clinical usability and application. This research aims to develop and validate risk prediction models and from them create clinician-friendl ....People with chronic kidney disease have increased risk of cardiovascular events and mortality. Establishing predictors of these events can identify individuals most at risk and stratify therapy. Modifying risks reduces the progression of disease in people with chronic kidney disease. Risk prediction modelling has been done, but is not validated and requires clinical usability and application. This research aims to develop and validate risk prediction models and from them create clinician-friendly interfaces.Read moreRead less
A Novel Endogenous Inhibitor For The Treatment Of Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$774,606.00
Summary
In various kidney diseases including the most common cause of end stage kidney disease, diabetic nephropathy, identifying the molecular mechanisms responsible for kidney failure are needed to assist in defining new targets and to develop more effective treatments. The proposed studies highlight the potential of a naturally occurring endogenous molecule called Lipoxin, as a modulator of kidney injury which may provide us with a novel approach to tackle the problem of diabetic nephropathy.
Vitamin D And Chronic Kidney Disease: The Effects On Mineral Metabolism, Vascular Calcification And Transplant Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$103,582.00
Summary
Kidney disease is a major health issue in the community. Vitamin D deficiency has been associated with an increased burden of cardiovascular disease and mortality in these patients. Vitamin D also has been shown to have a significant role in modulating our immune system. This study aims to assess the potential of vitamin D therapy to reduce the burden of cardiovascular disease and its effects on the immune function of renal transplant recipients in the laboratory and clinical setting.
We have validated CDA1 as an effective target to retard kidney disease in diabetes using a mouse model where we deleted the CDA1gene. We have also developed a novel agent to inhibit CDA1 in order to retard diabetic kidney disease. In this application, we propose to confirm the efficacy of targeting CDA1 using various diabetes models and a range of strategies to target CDA1. We will also rigorously explore translation of these findings to a new treatment for diabetic renal disease.
Through this project, I will determine how diet and physical activity can improve the health and quality of life of people suffering from chronic kidney disease. I will also assess whether lifestyle interventions have the potential to prevent chronic kidney disease. My results will directly impact the lives of people with kidney disease and could lead to public health interventions to prevent kidney disease.
Improving Health Outcomes For Aboriginal And Torres Strait Islander Australians With Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$383,684.00
Summary
Based in Darwin, Dr Hughes’ research focuses on improving the health and wellbeing of Aboriginal and Torres Strait Islander peoples at risk of chronic kidney disease (CKD), and those with established Chronic and end-stage kidney disease. These studies focus on participants based in both community and hospital based populations. New areas of clinical research will be addressed, as well as health systems strengthening in both primary and tertiary care systems.
Lefty - A Novel Anti-fibrotic Molecule For The Treatment Of Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$425,920.00
Summary
Patients with progressive forms of kidney disease go on to develop end-stage renal failure which requires intensive medical support of dialysis or organ transplantation. This is an increasingly common condition in Australia, and the Western world in general. It is devastating for the individual and it places an enormous economic strain upon our healthcare system. In addition, renal failure is a strong and independent risk factor for cardiovascular disease. Current treatments can at best slow the ....Patients with progressive forms of kidney disease go on to develop end-stage renal failure which requires intensive medical support of dialysis or organ transplantation. This is an increasingly common condition in Australia, and the Western world in general. It is devastating for the individual and it places an enormous economic strain upon our healthcare system. In addition, renal failure is a strong and independent risk factor for cardiovascular disease. Current treatments can at best slow the rate of progression of kidney disease, but cannot prevent the relentless progression to end-stage renal failure. Thus, there is a major medical need to be able to halt, and hopefully reverse, this relentless disease. Scarring of the kidney (termed fibrosis) is the common final pathway leading to end-stage renal failure regardless of the nature of the underlying kidney disease. Our preliminary studies have shown that a naturally occurring protein called Lefty can act to inhibit renal fibrosis in cell culture and animal studies. These very promising results have lead to the hypothesis that Lefty can halt, and perhaps even reverse, scarring of the kidney in progressive kidney disease. We will test this hypothesis by using Lefty as a treatment in animal models of renal fibrosis. Further cell culture studies are also planned to examine the mechanisms by which Lefty modulates renal fibrosis. If successful, these studies will provide critical data to support the development of Lefty as a clinical treatment for patients with progressive forms of kidney disease.Read moreRead less
Epithelial-mesenchymal Transformation In Diabetic Nephropathy: Roles Of Oxidative Stress And KLF Transcription Factors
Funder
National Health and Medical Research Council
Funding Amount
$557,523.00
Summary
Diabetes mellitus is responsible for the majority of kidney disease in the Western world . Diabetic nephropathy now accounts for the single largest cost to the health system in the USA. In Australia diabetic nephropathy, together with glomerulonephritis accounts for over 50% of the cases of dialysis-requiring renal failure. As the incidence of diabetes is increasing, current projections indicate an expotential rise in patient population with kidney disease. As the presence of kidney dysfunction ....Diabetes mellitus is responsible for the majority of kidney disease in the Western world . Diabetic nephropathy now accounts for the single largest cost to the health system in the USA. In Australia diabetic nephropathy, together with glomerulonephritis accounts for over 50% of the cases of dialysis-requiring renal failure. As the incidence of diabetes is increasing, current projections indicate an expotential rise in patient population with kidney disease. As the presence of kidney dysfunction is possibly the greatest predictor of subsequent cardiovascular events (including heart attack, heart failure and stroke) a thorough understanding of the mechanism of progressive kidney failure in patients with diabetes is required so that effective therapeutic strategies may be developed. Preliminary data leading to the development of this proposal, has shown that normal kidney tubule cells 'transform' into fibroblastic-like cells, in a process known as epithelial-mesenchymal transformation (EMT), under the metabolic disturbances inherent in diabetes mellitus. These fibroblast-like cells are likely to be responsible for the progressive scarring in the kidney that is characteristic of irreversible renal failure. We have documented that a specific factor, transforming growth factor beta (TGFB1) is increased in kidney cells in the presence of diabetes mellitus, and our preliminary data suggests the action of TGB1 is regulated by the KLF-family of transcription factors. This project aims to determine whether metabolic conditions such as exposure to high glucose and oxidative stress induced by diabetes mellitus modifies the KLF factors within cells that then alter susceptibility to TGFB1 induced EMT. The specific pathways involved in EMT will be dissected using both cell culture models and animal models of diabetes mellitus. These pathways will be selectively interrupted to assess reversibility of the EMT process.Read moreRead less