Role Of JNK And P38 MAPK Signalling In Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$454,500.00
Summary
Renal failure is a major health problem in our community. Patients who progress to end-stage renal failure are dependent upon lifelong dialysis or transplantation (an expensive and complex treatment). The past decade has seen a dramatic increase in the number of patients developing end-stage renal failure, mainly due to increasing rates of diabetic kidney disease. Indeed, the recent AusDiab nationwide survey that identified diabetes or glucose intolerance (a precursor to diabetes) is now present ....Renal failure is a major health problem in our community. Patients who progress to end-stage renal failure are dependent upon lifelong dialysis or transplantation (an expensive and complex treatment). The past decade has seen a dramatic increase in the number of patients developing end-stage renal failure, mainly due to increasing rates of diabetic kidney disease. Indeed, the recent AusDiab nationwide survey that identified diabetes or glucose intolerance (a precursor to diabetes) is now present in up to 25% of the adult Australian population. Around 50% of diabetics develop kidney disease and, despite recent advances in better control of blood glucose and blood pressure, kidney disease in most diabetic patients will inexorably progress to end-stage renal failure. Therefore, there is an urgent need to improve treatment strategies in diabetic patients to avoid kidney failure. We have identified a group of proteins (enzymes called JNK and p38) within cells that play a causal role in the development of non-diabetic forms of kidney disease. Most recently, we have shown that an increase in the activity of these proteins (JNK and p38) is associated with the development of human and experimental diabetic kidney disease. Therefore, this project will block the action of JNK and p38 using two complementary approaches (pharmaceutical drugs and genetically modified mice) to determine whether targeting these proteins can suppress the development of diabetic kidney disease. In addition, there is evidence to suggest that blockade of these proteins may have a beneficial impact upon insulin resistance and elevated blood glucose in type 2 diabetes. If these postulates are proven, this will provide a well-defined therapeutic target for the treatment of diabetic kidney disease, and perhaps diabetes itself. Furthermore, since inhibitors of these proteins are already in clinical trials for other indications, targeting this mechanism in diabetic kidney disease is a realistic goal.Read moreRead less
Apoptosis Signal-regulating Kinase 1 (ASK1) Is A Major Pathway Of Stress-induced Renal Injury In Different Types Of Progressive Kidney Disease.
Funder
National Health and Medical Research Council
Funding Amount
$678,865.00
Summary
Oxidative stress plays an important role in progressive kidney disease. We have identified a stress-activated mechanism (the ASK1 pathway) through which oxidative stress may cause kidney disease. We will perform preclinical studies in models of different types of kidney disease with an ASK1 inhibitor drug and genetically modified mice. These studies will provide new insights into the pathogenesis of kidney disease and will determine the potential of ASK1 as therapeutic target in kidney disease.
Defining The Central Role Of Podocyte Depletion In The Development, Progression And Management Of Glomerular Disease
Funder
National Health and Medical Research Council
Funding Amount
$690,855.00
Summary
Podocytes are key cellular components of the kidney’s filtration barrier. Podocyte depletion (cell loss or injury) is a key event in most forms of kidney disease. We will investigate interactions between podocyte depletion and two major risk factors for kidney disease (diabetes and hypertension), assess whether podocyte depletion influences therapeutic outcomes, and commence efforts to develop podocyte-specific therapies.
Generating Endogenous Antigen Specific T Regulatory Cells To Treat Autoimmune MPO-ANCA GN
Funder
National Health and Medical Research Council
Funding Amount
$885,566.00
Summary
Glomerulonephritis (GN) is an inflammatory disease that affects the filtering organs (glomeruli) of the kidney. The most severe and aggressive form is ANCA-associated GN resulting from loss of tolerance to myeloperoxidase (MPO). Current therapies are toxic. This study will develop new strategies to restore immune tolerance to MPO thus treating patients with this disease. We will use an animal model to provide proof-of-concept that these novel therapies can treat MPO-ANCA associated GN.
Selective Targeting Of Acute Renal Injury By Inhibition Of The Receptor Tyrosine Kinase, C-fms.
Funder
National Health and Medical Research Council
Funding Amount
$443,007.00
Summary
The progression of kidney disease to end-stage renal failure is a major health problem in our community. We have identified that macrophages, a type of white blood cell, plays an important role in causing inflammatory kidney injury. This project will use clinically relevant animal models to test the therapeutic potential of our new approach to selectively remove these cells from the inflamed kidney and thereby protect it from injury.
Cardiovascular Disease; Priorities And Outcomes For People With Chronic And End Stage Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$81,976.00
Summary
This thesis will investigate the patterns, causes and effects of heart disease in chronic kidney disease patients; how heart disease impacts on hospital admission patterns and mortality over time. We will explore the relationship between cognition, cardiovascular and kidney disease; the impact on patient outcomes and quality of life. Finally, we will explore how current research funding reflects disease burden, research output and the stated priorities of patients with chronic kidney disease.
Implementing Innovative Trial Methodologies For Chronic Disease
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Chronic kidney disease and diabetes are associated with increased cardiovascular disease, hospitalisation and mortality. Health can be improved through better delivery of care. I plan to perform a population based study to identify people with kidney disease or diabetes who do are not receiving optimal care as described in current guidelines. From this, I plan to develop a trial to close the gap. I also plan to assess whether data linkage is an accurate method to conduct trial follow-up.
The SHARP-ER Study: Extended Follow-up Of The SHARP Study Cohort
Funder
National Health and Medical Research Council
Funding Amount
$1,106,265.00
Summary
The SHARP study, conducted from 2003 to 2010, recruited over 9,000 participants with kidney disease and showed, for the first time, that cholesterol-lowering was effective in preventing heart and vascular disease in people with advanced kidney disease. This study will extend follow-up to answers critical questions regarding long-term cardiovascular, renal and other health outcomes.
Growing The Evidence Base For Improved Outcomes In Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$697,209.00
Summary
One in eight Australians has kidney disease, and is at increased risk of kidney failure, heart disease and stroke, and premature death. Despite this, very few treatments have been proven to be be effective at improving these outcomes. Professor Perkovic will undertake a suite of high-quality randomised trials and systematic reviews that will reliably identify new treatment approaches that will result in better quality and quantity of life for the millions of Australians affected by kidney diseas ....One in eight Australians has kidney disease, and is at increased risk of kidney failure, heart disease and stroke, and premature death. Despite this, very few treatments have been proven to be be effective at improving these outcomes. Professor Perkovic will undertake a suite of high-quality randomised trials and systematic reviews that will reliably identify new treatment approaches that will result in better quality and quantity of life for the millions of Australians affected by kidney diseaseRead moreRead less