Signalling Pathways In Antibody-Mediated Renal Injury
Funder
National Health and Medical Research Council
Funding Amount
$113,296.00
Summary
Many types of kidney disease are induced by antibody binding to the kidney which initiates a damaging response by cells of the immune system. Current therapies for such diseases rely upon toxic immunosuppressive drugs. This project will examine one specific mechanism by which immune cells are activated by antibody to cause injury in human and experimental renal injury. These studies will determine whether this specific mechanism is a suitable target for developing new therapeutic drugs.
Contributions Of Intrinsic Renal Cells To Inflammatory Renal Injury
Funder
National Health and Medical Research Council
Funding Amount
$66,433.00
Summary
These studies aim to improve our understanding of glomeruonephritis, the most common cause of kidney failure. They will study the interactions between circulating white blood cells (leukocytes) which originate from the bone marrow , and intrinsic kidney cells in the development of tis disease. Inflammation is the result of recruitment of bone marrow derived inflammatory cells and plasma proteins to a variety of stimuli. The subsequent injury represents the interaction between recruited cells and ....These studies aim to improve our understanding of glomeruonephritis, the most common cause of kidney failure. They will study the interactions between circulating white blood cells (leukocytes) which originate from the bone marrow , and intrinsic kidney cells in the development of tis disease. Inflammation is the result of recruitment of bone marrow derived inflammatory cells and plasma proteins to a variety of stimuli. The subsequent injury represents the interaction between recruited cells and local cells within the target organ. Glomerulonephritis is an important human disease where both bone marrow derived inflammatory and local cells have the potential to contribute to kidney injury by production of signalling molecules called cytokines. This study will determine the contribution of specific cytokines produced by intrinsic renal cells towards the development of inflammatory kidney injury in GN.Read moreRead less
Kidney disease occurs in up to 50% of patients with insulin-dependent (type 1) and non-insulin-dependent (type 2) diabetes. The increasing rate of diabetes in our community has made it a major cause of kidney disease and a growing health problem. Despite clinical attempts to control blood glucose and blood pressure levels, kidney disease in most diabetic patients progresses towards a complete loss of kidney function. In severe cases, the survival of the patient is dependent upon lifelong dialysi ....Kidney disease occurs in up to 50% of patients with insulin-dependent (type 1) and non-insulin-dependent (type 2) diabetes. The increasing rate of diabetes in our community has made it a major cause of kidney disease and a growing health problem. Despite clinical attempts to control blood glucose and blood pressure levels, kidney disease in most diabetic patients progresses towards a complete loss of kidney function. In severe cases, the survival of the patient is dependent upon lifelong dialysis or transplantation, which are costly and complicated treatments. Therefore, there is an urgent need to improve treatment stategies in diabetic patients to avoid kidney failure. Recent evidence in human and experimental models of diabetic kidney disease has indicated that macrophages infiltrate the kidney during the disease process. Our previous knowledge from other inflammatory kidney diseases suggests that macrophages play an important role in promoting the progression of disease and, in some of these diseases, treatment strategies which block macrophage function and accumulation have been shown to be effective in inhibiting the disease. The overall aim of these studies will be to determine the importance of macrophages in the pathogenesis of diabetic kidney disease and identify the mechanisms regulating their recruitment and activation within the diabetic kidney. This will be achieved by examining the progression of kidney disease in type 1 and type 2 diabetic mice which have been genetically modified to prevent macrophage accumulation and activation within the kidney. These studies will provide valuable information into the pathogenesis of diabetic kidney disease and will identify whether therapeutic strategies targeting macrophages can help prevent kidney loss in diabetes.Read moreRead less
MODIFICATION OF TUBULE CELL CYTOKINES REGULATING INTERSTITIAL INFLAMMATION IN CHRONIC PROTEINURIC RENAL DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$294,121.00
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 1500 Australians commence dialysis for this reason, and many more die of kidney failure or its complications. One of the major reasons for progression of kidney failure is that kidney cells produce a complex network of inflammatory mediators (cytokines) which attract inflammatory cells into the suppo ....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 1500 Australians commence dialysis for this reason, and many more die of kidney failure or its complications. One of the major reasons for progression of kidney failure is that kidney cells produce a complex network of inflammatory mediators (cytokines) which attract inflammatory cells into the supporting tissue of the kidney (the interstitium). Recently, drugs that inhibit these cytokines have been used in animal models of chronic kidney disease. Such treatment regimens have been at most only partially effective because they have been directed against only one cytokine, and because they have ignored the fact that the profile of cytokines varies with stage of disease. This project will use a rodent model (Adriamycin nephrosis) of human chronic kidney disease to define strategies for preventing interstitial inflammation using anti-cytokine therapy. Our laboratory has identified three cytokines which appear to play a pivotal role in the development of interstitial inflammation in Adriamycin nephrosis, and shown that their production varies with time. Knowledge of the time-dependent interactions among and regulation of these cytokines will be used to define optimal delivery of therapy directed against all three cytokines. As anti-cytokine therapy is already being trialled in other types of (non-kidney) disease in humans, the success of such a therapeutic approach to treating progressive kidney disease in this animal model will have important and immediate implications for the treatment of chronic kidney disease in humans.Read moreRead less