Defining Roles Of Innate Lymphoid Cells In Chronic Kidney Disease For Future Therapy
Funder
National Health and Medical Research Council
Funding Amount
$638,825.00
Summary
Chronic kidney disease is a major cause of death and morbidity in Australia. Current strategies that delay progression of kidney disease are limited. Innate lymphoid cells are a newly identified heterogeneous family of immune cells, which have important roles in tissue homeostasis and pathologic inflammation. The central aims of the project are to define the role of innate lymphoid cells in chronic kidney disease, and further to explore their therapeutic potential in kidney disease.
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.
Optimising The Therapeutic Efficacy Of Anti-inflammatory Macrophages For Use In Chronic Kidney Diseases
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Chronic kidney disease (CKD) is a major cause of death and morbidity in Australia. Current treatments that are able to delay progression for CKD are limited. As a consequence, more than 2300 additional Australians need kidney replacement each year and many more die of kidney failure. We have reduced and prevented injury in a mouse model of CKD by administering protective white blood cells - macrophages. This project will modify macrophages ex vivo to optimize them for use as a therapy for CKD.
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
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
The Role Of Toll-like Receptors In Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$740,452.00
Summary
Diabetic nephropathy (DN) is the leading cause of chronic kidney disease globally and the No.1 cause of kidney failure requiring dialysis or transplantation in Australia. We are unsure why kidney scarring and failure develops in people with diabetes. Because of this, we have no specific treatments. Our studies suggest an immune receptor present in the kidney may be important. We aim to see whether absence of these receptors can prevent DN, thus identifying a specific target for treatment.
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.
Progression Of Kidney Damage In Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$782,249.00
Summary
There is an overwhelming burden of chronic disease in Indigenous Australians. In order to attempt to improve kidney disease in this high-risk population, it is vital that we understand what factors contribute to rapid progression of kidney damage. This study will provide the evidence to design an intervention to slow progression of kidney disease in Indigenous Australians. It will also enable development of appropriate clinical guidelines for improved management of kidney 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.
Negative Modulators Of Leucocyte Recruitment In The Kidney. The Role Of Slit And Robo.
Funder
National Health and Medical Research Council
Funding Amount
$368,100.00
Summary
Kidney failure is a major health problem in our community, affecting the lives of several thousand individuals and their families. Every year in Australia, about 2,000 new individuals commence dialysis and require ongoing treatment for the rest of their lives. The significant negative impact kidney failure has on quality of life and on life expectancy added to the major shortage of transplant organs, makes the development of effective therapies for kidney diseases an important goal. Our current ....Kidney failure is a major health problem in our community, affecting the lives of several thousand individuals and their families. Every year in Australia, about 2,000 new individuals commence dialysis and require ongoing treatment for the rest of their lives. The significant negative impact kidney failure has on quality of life and on life expectancy added to the major shortage of transplant organs, makes the development of effective therapies for kidney diseases an important goal. Our current therapies have major limitations in terms of their effectiveness and side effects. New therapies which can prevent the progression of kidney disease or prolong the survival of transplanted kidneys may, therefore, have enormous benefits. In order for this to occur, an improved understanding of the common factors underlying kidney disease is required. Our recent studies have been examining the factors influencing kidney inflammation. This process is a significant cause of long term damage in various kidney diseases and in kidney transplants. Our work has identified a potentially major role for recently discovered molecules known as Slit proteins in preventing or decreasing inflammation in the kidney. The level of expression of these molecules in the kidney appears to be rapidly decreased in kidney inflammation and their protective effect is then lost. This imbalance appears to promote the disease process and may be a useful target for the treatment of certain kidney diseases. Our work has found that Slit proteins are able to decrease the movement of white cells (the cells which cause inflammation) out of the blood circulation and into the kidney. The proposed studies aim to better understand the role of these molecules in the kidney as naturally expressed anti-inflammatory agents and to test their potential as therapeutic agents. We hope that the information obtained from these studies will help in the development of new therapies to manage various forms of kidney disease.Read moreRead less