Role Of The Lysosomal Protein SCARB2 In Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$475,658.00
Summary
Loss of protein in the urine is one of the most important things that happens before the kidneys fail. Losing protein seems to damage the kidneys, but we are still not sure how it happens in most people. We are studying the 'waste management system' of cells, that enables them to get rid of proteins that are no longer required. We have some evidence that this system is abnormal in inherited proteinuria and now want to find out if this is also a problem in more common diseases.
Kidney failure is a major health disorder in Australia and with more diabetes the number of patients waiting for transplant on dialysis is increasing. Current treatments give good initial survival of the kidney transplant but most kidneys are lost due to chronic damage . We propose a number of tolerance strategies in a model of kidney transplantation that will allow transplantation without longterm immunosuppression.
To investigate alternative strategies to treat end stage renal disease we have transplanted embryonic kidneys into the wall of the abdominal cavity of adult hosts where they become vascularised and undergo continued but limited development. Strategies to enhance their growth-development and decrease immunogenicity-rejection will now be determined, and the origin of a 'ureter-like' tube of tissue that grows to connect the transplanted embryonic kidney with the recipient bladder investigated.
Understanding The Mechanistic Basis Of Microalbuminuria In Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$613,757.00
Summary
The appearance of small amounts of albumin in the urine (microalbuminuria) in people with diabetes is a marker of progressive kidney disease, while microalbuminuria in the general population is a major risk factor for cardiovascular disease. The reason why microalbuminuria develops is poorly understood. This project will investigate dysfunction of kidney tubular cells as the mechanistic basis of microalbuminuria. If proven, this will provide a new link between kidney and cardiovascular disease.
A Central Role For Carbonic Anhydrase In Renal Hypertrophy And Interstitial Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$414,888.00
Summary
1 in 3 Australians are at risk of developing kidney disease. Renal replacement therapies (dialysis and transplantation) currently cost over $1.2 billion per year. These therapies do not address the underlying cause of the disease. Much research has focused on novel strategies to reverse kidney damage with mixed success. In this project we examine a novel preventative strategy based on currently available therapeutics that may slow the progression of kidney disease.
The Role Of IL-18 In Proliferative And Crescentic Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$56,177.00
Summary
Inflammation of the small filters with the kidneys, known as glomerulonephritis, is the commonest cause of kidney failure in Australia. People whose kidneys have failed need either kidney dialysis or a kidney transplant. Our understanding of the immune events that cause glomerulonephritis is patchy. However, it is known that T cells are the directors of immune responses in the body and direct the immune response in glomerulonephritis. Chemical messengers known as cytokines direct the way T cells ....Inflammation of the small filters with the kidneys, known as glomerulonephritis, is the commonest cause of kidney failure in Australia. People whose kidneys have failed need either kidney dialysis or a kidney transplant. Our understanding of the immune events that cause glomerulonephritis is patchy. However, it is known that T cells are the directors of immune responses in the body and direct the immune response in glomerulonephritis. Chemical messengers known as cytokines direct the way T cells behave. One of these cytokines, known as interleukin-18, has been shown to stimulate T cells and other immune cells to induce inflammation that is helpful when the body is fighting infection but is harmful in immune diseases. This project will determine the role of interleukin-18 in glomerulonephritis by studying the way it talks to T cells and the mechanisms by which it incites inflammation in the kidney. Mice with glomerulonephritis will be treated by blocking the actions of interleukin-18 to discover whether interleukin-18 produced by the animal is important in kidney damage induced by glomerulonephritis, to understand the way in which this cytokine works and to assess whether blocking interleukin-18 could be a useful treatment for glomerulonephritis in humans. Current treatments for glomerulonephritis are often ineffective and have unwanted side effects. Knowledge of the way interleukin-18 participates in the immune response in glomerulonephritis may lead directly or indirectly to more effective and more targeted treatments for different forms of glomerulonephritis.Read moreRead less
TAK1 - A Novel Regulator Of Renal Inflammation And Fibrosis.
Funder
National Health and Medical Research Council
Funding Amount
$537,704.00
Summary
Renal failure is a major health problem in our community. Recent in vitro studies have identified a protein that plays a critical role in the induction of inflammation and fibrosis - processes central to the progression of kidney disease. This project will use a genetic-based approach to determine if this regulator plays a critical role in the pathogenesis of experimental kidney disease. If successful, these studies will identify a new therapeutic target for the treatment of kidney disease.
A Randomised Controlled Trial Of High Dose Folic Acid To Slow The Progression Of Atheroma In Renal Failure (194246)
Funder
National Health and Medical Research Council
Funding Amount
$326,980.00
Summary
The Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) is examining the effect of high dose folic acid supplementation on the development of desease of the heart and blood vessels in people with kidney failure. Subjects in the study take 15mg folic acid daily or a dummy tablet for 3 to 5 years. Folic acid is known to reduce the levels of a substance called homocysteine which is elevated in people with kidney disease. Homocysteine has been associated with disease of the heart and blood ....The Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) is examining the effect of high dose folic acid supplementation on the development of desease of the heart and blood vessels in people with kidney failure. Subjects in the study take 15mg folic acid daily or a dummy tablet for 3 to 5 years. Folic acid is known to reduce the levels of a substance called homocysteine which is elevated in people with kidney disease. Homocysteine has been associated with disease of the heart and blood vessels and these diseases occur very commonly in people who also have kidney failure. I t is hoped that by using folic acid to reduce the levels of homocysteine, we can reduced the amounbt of heart and blood vessel disease in people with kidney failure.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