Costimulation In Progressive Non-immune Tubulointerstitial Renal Disease.
Funder
National Health and Medical Research Council
Funding Amount
$434,875.00
Summary
Current treatments for chronic kidney disease are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year about 1700 Australians commence dialysis for this reason and many more die of kidney failure or its complications. This project will examine the role of costimulatory molecules in causing chronic kidney disease (CRD) to progress and their potential as targets for specific ....Current treatments for chronic kidney disease are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year about 1700 Australians commence dialysis for this reason and many more die of kidney failure or its complications. This project will examine the role of costimulatory molecules in causing chronic kidney disease (CRD) to progress and their potential as targets for specific therapy to slow the progression of CRD. In chronic kidney diseases of all types, the kidney becomes infiltrated with inflammatory cells. The amount of inflammation has an important bearing on the severity of kidney failure and the rate at which kidney disease progresses. There are a range of different cells that invade the inflamed kidney, some may worsen disease while some may protect against it. Current treatments are non-selective and may, by suppressing inflammation, prevent both repair and protection. Costimulatory molecules have been shown to be important in the regulation of inflammatory cell activation in transplantation and some autoimmune diseases. We, and others, have evidence to suggest that costimulatory molecules may be pivotal to the development and progression of kidney inflammation in CRD as well. This project will use two robust animal models of human CRD to define the role of costimulatory molecules in progression of kidney disease. If, as our preliminary evidence suggests, costimulatory molecules are shown to alter disease progression, then they will provide excellent targets for new treatments. Eventually, treatment directed against costimulatory molecules may be used as more effective and safer therapy for human kidney disease.Read moreRead less
Treatment Of Diverse Renal Diseases With Regulatory Cells
Funder
National Health and Medical Research Council
Funding Amount
$566,946.00
Summary
Chronic kidney disease (CKD) is a major cause of death and disability in the Australian population. Current treatments for CKD are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or tranplantation to remain alive. Every year more than 1700 Australians require kidney replacement therapy for this reason and many more die of kidney failure or its complications. Some forms of kidney disease are self-limited whereas oth ....Chronic kidney disease (CKD) is a major cause of death and disability in the Australian population. Current treatments for CKD are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or tranplantation to remain alive. Every year more than 1700 Australians require kidney replacement therapy for this reason and many more die of kidney failure or its complications. Some forms of kidney disease are self-limited whereas others are characterised by chronic kidney scarring and the eventual development of endstage disease. This project will explore whether natural protective cells (regulatory T cells) can be used to treat differing types of CKD, including those characterised predominantly by inflammation or by fibrosis. In addition, the protective mechanisms of regulatory T cells (including their interaction with resident kidney cells) will be explored, as will ways of increasing the efficacy of regulatory T cell therapy.Read moreRead less
Preventing Kidney Fibrosis By Targeting Matrix Metalloproteinase-9 In Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$516,972.00
Summary
More than 2300 Australians commence kidney replacement therapy each year and many more die of kidney failure or its complications. Kidney fibrosis is the final pathway of damage in all chronic kidney diseases. Our data demonstrates that a matrix enzyme MMP-9 is likely to be an important cause of kidney fibrosis. We aim to investigate mechanisms by which MMP-9 causes kidney fibrosis, and develop strategies involving inhibition of MMP-9 to prevent kidney fibrosis.
Renal failure is a major cause of morbidity and mortality in persons with diabetes mellitus and accounts for the majority of renal disease worldwide. Renal fibrosis is the end result of progressive kidney disease. The proposed research aims to identify a new strategy by targeting specific channels in kidney cell membranes to arrest the development of enal fibrosis and hence progressive kidney disease caused by diabetes mellitus.
Kidney Injury As A Determinant Of Macrophage Phenotype And Efficacy For Treating Chronic Kidney Disease (CKD)
Funder
National Health and Medical Research Council
Funding Amount
$548,341.00
Summary
Chronic kidney disease (CKD) is a major cause of death and disability in the Australian population. Current treatments for CKD are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or tranplantation to remain alive. Every year more than 1700 Australians require kidney replacement therapy for this reason and many more die of kidney failure or its complications. Macrophage infiltration of kidneys is characteristic of C ....Chronic kidney disease (CKD) is a major cause of death and disability in the Australian population. Current treatments for CKD are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or tranplantation to remain alive. Every year more than 1700 Australians require kidney replacement therapy for this reason and many more die of kidney failure or its complications. Macrophage infiltration of kidneys is characteristic of CKD, and it has been assumed that macrophages cause damage. However, we have shown that certain types of macrophages can reduce kidney damage. This project will explore whether macrophage type can be switched from that causing damage to that reducing injury, with the aim of using this approach to treat CKD.Read moreRead less
A Novel And Unique Protein I-body For The Treatment Of Chronic Kidney Disease Through Targeting CXCR4
Funder
National Health and Medical Research Council
Funding Amount
$768,340.00
Summary
Chronic kidney disease (CKD) is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease, and premature death. Kidney transplantation and dialysis are the only options for the management of CKD, which results in a significant burden on the health system. The central aim of this project is to develop a novel therapeutic strategy to limit/reverse CKD, which will lead to a researcher-industry partnership in discovery of novel therapeutic agent.
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.
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
Gamma-Delta Tregs, CD8 Tregs And Selected Natural Tregs To Treat Renal Injury
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Chronic kidney disease (CKD) progresses due to ongoing damage to the kidney. We have identified three types of white cells that can reduce kidney damage in CKD. The first is a unique set of gamma-delta T cells that expand in the kidney and protect against injury. The second is a restricted set of CD8 T cell that can protect against kidney injury. The third are targeted natural regulatory T cells. These studies develop each of these three subsets as potential cellular therapies in CKD.
Vitamin D3 Receptor Signalling To Prevent Kidney Failure Due To Polycystic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$468,009.00
Summary
Polycystic kidney disease (PKD) is the most common fatal inherited kidney disease in the world. Kidney failure is the most serious and life-threatening complication of PKD, but currently there is no treatment to prevent this problem. The aim of this project is to determine whether vitamin D3 can prevent kidney failure and hypertension due to PKD. The results of this project could lead to simple and cost-effective treatments to prevent kidney failure in patients suffering from PKD.