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
Identifying Donor And Recipient Gene Pathways In Renal Transplant Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,082,069.00
Summary
We have identified a 13 gene set that predicts renal transplant fibrosis and graft loss in patients. Interestingly some of these gene are donor as well as recipient related. In this project we aim to investigate these gene pathways in cell lines and animal models to better understand how the cause of renal fibrosis after transplantation.
EFFECTOR AND REGULATORY INTERSTITIAL INFLAMMATORY CELLS IN CHRONIC PROTEINURIC RENAL DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$289,150.00
Summary
Current treatments for chronic kidney disease are ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year almost 1600 Australians commence dialysis for this reason, and many more die of kidney failure or its complications. This project will lead to a greater understanding of why kidney failure progresses, and will define more effective treatments for preventing progression. In progressive chronic kidney ....Current treatments for chronic kidney disease are ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year almost 1600 Australians commence dialysis for this reason, and many more die of kidney failure or its complications. This project will lead to a greater understanding of why kidney failure progresses, and will define more effective treatments for preventing progression. In progressive chronic kidney diseases of all types, the supporting tissue within the kidney (the interstitium) becomes infiltrated with inflammatory cells. The amount of interstitial inflammation has an important bearing on the severity of kidney failure, and the rate at which kidney disease progresses to endstage. The reasons that these inflammatory cells infiltrate the interstitium, and their exact role in the progression of kidney disease are only partially understood. For example, some of these inflammatory cells appear to cause kidney scarring, whereas others appear to be protective. Moreover, even though they are obvious targets for treatment aimed at slowing the progression of kidney disease, current treatments are largely ineffective as they do not differentiate between the different types of inflammatory cells, and whether these cells are causing or preventing damage. Our laboratory has recently developed a robust model of chronic kidney disease, which will be used to examine the effect of individual types of interstitial inflammatory cells on the progression of kidney disease. So far we have shown that depletion of one type of inflammatory cell (CD4 lymphocytes) worsened the disease process, whereas depletion of two other cell types (CD8 lymphocytes or macrophages) was protective. This raises the real and exciting possibility that treatment directed against specific inflammatory cells may be effective in the treatment of progressive kidney disease in humans.Read moreRead less
Treatments For Glomerulonephritis That Harness Antigen Specific Regulatory Cells
Funder
National Health and Medical Research Council
Funding Amount
$610,005.00
Summary
Many forms of kidney disease are caused by the immune system targeting the kidney. We now have new data that demonstrate that these forms of autoimmune glomerulonephritis are caused by an imbalance in the numbers of kidney specific inflammatory versus regulatory cells. This project seeks to test therapies that correct that imbalance by increasing the numbers of kidney specific regulatory cells.
Inflammation of the kidneys is an important, yet poorly understood cause of kidney disease in Australia. This project will define the role of some of the immune cells, called Th17, that usually act to protect us from infection, but can turn rouge and may cause kidney damage.
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
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.
The Role Of Th1 Immune Responses & Inflammatory Cytokines On Cardiovascular Disease & Arterial Function In End-Stage Renal Disease & Their Response To Different Dialysis Modality
Funder
National Health and Medical Research Council
Funding Amount
$48,787.00
Summary
The immune system and inflammatory molecules are important factors in cardiovascular disease in the general population. These inflammatory molecules are also present in patients with end-stage kidney disease, a condition in which cardiovascular disease is excessively prevalent and the leading cause of death. We aim to use laboratory, animal and clinical studies to demonstrate the role of inflammation in cardiovascular disease in patients with kidney failure, and their response to dialysis.
Targeting Renal And Vascular Inflammation In Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$781,589.00
Summary
Inflammation is a hallmark of high blood pressure (A.K.A. hypertension) and underlies clinical complications of the condition such as kidney failure and blood vessel disease. This project will investigate whether a recently described signaling complex termed the 'inflammasome' is a trigger of inflammation in hypertension in the hope of identifying it as a target for new drugs that are more effective in the treatment of hypertension and its complications.