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.
The IDEAL Trial - Initiating Dialysis Early And Late
Funder
National Health and Medical Research Council
Funding Amount
$752,500.00
Summary
Kidney replacement therapy by dialysis has in the past been provided for patients with endstage renal failure once their remaining kidney function has deterioriated to less than 5-10% of normal. There has been an increasing trend in recent years to offer dialysis therapy at an earlier stage of kidney failure, such that more than 20% of dialysis patients in Australia (and up to 35% in some subgroups) now commence that therapy when their remaining kidney function is greater than 10%. This change h ....Kidney replacement therapy by dialysis has in the past been provided for patients with endstage renal failure once their remaining kidney function has deterioriated to less than 5-10% of normal. There has been an increasing trend in recent years to offer dialysis therapy at an earlier stage of kidney failure, such that more than 20% of dialysis patients in Australia (and up to 35% in some subgroups) now commence that therapy when their remaining kidney function is greater than 10%. This change has occurred because of the unproven belief that earlier dialysis may be associated with a better health outcome. However, dialysis treatment is associated with complications and it is very expensive. Therefore, it is important to determine the health and economic consequences of commencing dialysis early rather than late. The IDEAL trial (Initiating Dialysis Early And Late) is a large multi-centre study being conducted in many renal units in Australia and New Zealand, which will determine whether it is better, in terms of health outcomes and total cost of treatment, to commence dialysis at a time when remaining kidney function is between 10 and 14% or between 5 and 7% of normal.Read moreRead less
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
Molecular Mechanisms Of Macrophage-mediated Renal Injury.
Funder
National Health and Medical Research Council
Funding Amount
$59,756.00
Summary
The complete loss of kidney function means that survival of the patient is dependent upon lifelong dialysis or a kidney transplant. Dialysis patients have a poor quality of life, and the provision of dialysis and transplantation treatments are very costly. Our current therapies reply upon steroids and cytotoxic drugs. These therapies have only limited efficacy and are associated with significant side-effects. Therefore, we need to develop new and specific approaches to the treatment of kidney di ....The complete loss of kidney function means that survival of the patient is dependent upon lifelong dialysis or a kidney transplant. Dialysis patients have a poor quality of life, and the provision of dialysis and transplantation treatments are very costly. Our current therapies reply upon steroids and cytotoxic drugs. These therapies have only limited efficacy and are associated with significant side-effects. Therefore, we need to develop new and specific approaches to the treatment of kidney disease. To do this, we need to begin by understanding the way in which the kidney is damaged in disease. Our studies have shown that white blood cells, called macrophages, enter the kidney in large numbers during disease. Indeed, the greater the number of macrophages within the kidney, the more severe the kidney injury. We believe, one the basis of animal studies, that these macrophages cause kidney injury. However, we do not know the mechanisms by which this happens. To address this question, we have developed a rat model of kidney disease in which we can take macrophages, which we have cultured in the laboratory, and inject them into animals and they will enter the kidney and cause injury. This allows us to modify specific macrophage functions in culture and then determine whether this affects the ability of these macrophages to cause kidney injury in the animal. In this way, we will be able to understand the mechanisms by which macrophages cause kidney injury. We hope that these studies will enable us to develop new and specific approaches to the treatment of human kidney disease.Read moreRead less
HB-EGF Promotes Recovery From Experimental Acute Renal Failure
Funder
National Health and Medical Research Council
Funding Amount
$337,374.00
Summary
Kidney failure is a frequent complication of serious injury or illness. Although the kidneys generally recover, this can take some time. Before they recover, the inability of the kidneys to function normally adds significantly to the suffering and debility of these sick people. The question we wish to ask is how do the kidneys repair themselves? Ultimately, we would like to know how we could speed up this process. It seems that the kidney remodels after injury by increasing production of growth ....Kidney failure is a frequent complication of serious injury or illness. Although the kidneys generally recover, this can take some time. Before they recover, the inability of the kidneys to function normally adds significantly to the suffering and debility of these sick people. The question we wish to ask is how do the kidneys repair themselves? Ultimately, we would like to know how we could speed up this process. It seems that the kidney remodels after injury by increasing production of growth factors, which are specialised proteins that tell the kidney cells what to do. If we could determine which of these was the most important then it might be possible to give it to patients. If we could even find out how these growth facotrs work, then it might be possible to replace them with a drug that could be more easily administered than a protein.Read moreRead less
The Role Of The Cytoplasmic Domain Of Tissue Factor In Maintenance Of The Glomerular Filtration Barrier.
Funder
National Health and Medical Research Council
Funding Amount
$487,066.00
Summary
This research aims to understand mechanisms of normal kidney function and the development of chronic kidney damage associated with diseases such as nephritis and diabetes. These diseases represent a significant burden of illness in Australia.
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
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.