Many different diseases can cause chronic kidney failure. Mast cell participation in most of these is prominent. These cells traditionally regarded as important only in allergy are now known to be capable of inducing injury in many other situations. The availability of safe drugs to block mast cell function makes determination of the role of mast cells in chronic kidney diseases important.
Intravascular Coagulopathy In Discordant Xenotransplantation
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly is to replace that organ with a new one ie. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there i ....The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly is to replace that organ with a new one ie. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there is no mechanical substitute. If these patients do not receive a transplant, they die. A solution to this problem is to use organs from animals. This is called xenotransplantation. The pig is the most suitable donor, however despite many similarities to humans which make it suitable, there are many differences which are still to be overcome before clinical application is possible. These differences are at a very fine molecular level and prevent the normal integration of the organ into the new recipient. The result is that the new organ is rejected within minutes. This process is called hyperacute rejection and by research into its mechanism it was found to be due to just a few differences. We and others have genetically modified pigs so that they have the human components and this has completely prevented this form of rejection. However,we have found a second barrier which causes a rejection response after a few days. It is now known that a major component of the cause of this second barrier is a few differences in the clotting system. We propose to make further genetic modifications which we think will prevent this rejection. This project proposes to examine various genetic modifications and test their effect in small animal models before going on to make and test pigs in which human anti-clotting genes have been inserted. . If we are successful, the possibility of replacing failed human organs with animal organs will be a step closer.Read moreRead less
Intravascular Coagulopathy In Discordant Xenotransplantation
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly, is to replace that organ with a new one ie. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there ....The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly, is to replace that organ with a new one ie. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there is no mechanical substitute. If these patients do not receive a transplant, they die. A solution to this problem is to use organs from animals. This is called xenotransplantation. The pig is the most suitable donor, however despite many similarities to humans which make it suitable, there are many differences which are still to be overcome before we can use xenotransplants clinically. These differences are at a very fine molecular level and prevent the normal integration of the organ into the new recipient. The result is that the new organ is rejected within minutes. This process is called hyperacute rejection and by research into its mechanism it was found to be due to just a few differences. We and others have genetically modified pigs so that they have the human genes and this has completely prevented this form of rejection. However,we have found a second barrier which causes a rejection response after a few days. It is now known that a major component of the cause of this second barrier is a few differences in the clotting system. We propose to make further genetic modifications which we think will prevent this rejection. This project proposes to examine various genetic modifications and test their effect in small animal models before going on to make and test pigs into which human genes have been inserted. If we are successful, the possibility of replacing failed human organs with animal organs will be a step closer.Read moreRead less
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.
Tubulointerstitial Epigenetics- The Underlying Basis Of Progressive Fibrosis In Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$378,940.00
Summary
Although the kidney has capacity to repair after mild injuries, ongoing or severe injury results in scarring (so-called fibrosis) and a progressive loss of kidney function. Understanding the mechanisms that regulate the transition from repair to fibrosis is important, because once fibrosis is initiated it can be extremely difficult to switch off or reverse.
Immunotherapeutic Strategies In Anti Myeloperoxidase ANCA Associated Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$615,998.00
Summary
Kidney disease is the 10th most common cause of death in Australia. Glomerulonephritis (GN) is a major cause of kidney disease. Autoimmunity underpins disease in most patients with the most severe forms. Following the discovery of the peptide that is the target of this autoimmunity promising new biological treatments are possible. This grant will assess the capacity of four emerging therapies to turn off injurious autoimmunity and treat disease.
CKD-FIX: A Randomised, Controlled Trial Of Allopurinol In The Slowing Of Kidney Disease Progression
Funder
National Health and Medical Research Council
Funding Amount
$1,917,147.00
Summary
Chronic kidney disease (CKD) is a major public health problem affecting over 1.5 million Australians and is associated with increased risk of death, heart disease and progression to end-stage kidney disease (ESKD). Current treatments to slow progression to ESKD are limited. The CKD-FIX trial aims to find out whether treatment with allopurinol, a commonly used drug for gout prevention, safely and effectively slows CKD progression. This could lead to significant health and economic benefits.
The Therapeutic Role Of Complement Inhibition In ANCA Associated Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$600,964.00
Summary
ANCA associated vasculitis is an inflammatory disease involving the kidney filters which is a major cause of chronic kidney failure. Current drugs to treat it are toxic. Less toxic treatments are required. In this study we will explore the potential for new treatments targeting complement (a normal blood protein involved in inflammation) to attenuate this disease in mice. We hope to define the role of complement in this disease and the benefits of inhibiting it before we use it in humans.
The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly is to replace the organ with a new one i.e. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there i ....The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly is to replace the organ with a new one i.e. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there is no mechanical substitute. If these patients do not receive a transplant, they die. A solution to this problem is to use organs from animals. This is called xenotransplantation. The pig is the most suitable donor, however despite the many similarities to humans which make pigs suitable, there are many differences which are still to be overcome before we can use pig xenotransplants clinically. These differences are at a very fine molecular level and prevent the normal integration of the pig organ into the human recipient. It is well established that the single most important difference which causes this rejection is a sugar molecule like a blood group which pigs have but humans do not. This is called Gal. This is also present in most animal species and we have completely removed it from a strain of mice by genetic modification. Unfortunately it has not been possible to make this change in pigs. However, the genetically modified mice give us a test model to determine precisely how much and by what mechanisms the Gal antigen is responsible for the rejection process.Read moreRead less
The Role Of Bone Morphogenetic Proteins In The Pathogenesis Of Pulmonary Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$236,540.00
Summary
Many people develop problems with the blood vessels in the lungs, which then leads to a narrowing of these vessels and consequently a back-pressure strain on the heart. These disorders can arise from inherited diseases of the blood vessels themselves, or from accquired lung disease (for example due to smoking or chronic infections). At present there are few treatments which have any benefits for these patients and many must undergo lung or heart-lung transplantation. This project is desigened bo ....Many people develop problems with the blood vessels in the lungs, which then leads to a narrowing of these vessels and consequently a back-pressure strain on the heart. These disorders can arise from inherited diseases of the blood vessels themselves, or from accquired lung disease (for example due to smoking or chronic infections). At present there are few treatments which have any benefits for these patients and many must undergo lung or heart-lung transplantation. This project is desigened both to find out new information about the disease process that affects the lung blood vessels and to offer a strategy for new treatments. The project will use a crippled form of the cold virus to deliver genes to the lining of the lung blood vessels, then see what impact that has on the pressure within the vessels and the ways in which they respond to certain stresses. These studies will be carried out using laboratory animals. If successful, it may be possible to eventually design such viruses to deliver genes which have a helpful therapeutic impact on the disease in patients.Read moreRead less