NEPHROTOXICITY OF ANGIOTENSIN INHIBITION DURING RENAL DEVELOPMENT
Funder
National Health and Medical Research Council
Funding Amount
$210,990.00
Summary
Renal dysplasia and renal cystic disease remain significant clinical problems in the paediatric population. Initial animal experiments have demonstrated that inhibiting the renal vasoactive peptide angiotensin during development results in a form of medullary cystic disease. The experiments in this project are aimed at understanding the specific roles and interactions that angiotensin plays in renal development, particularly in development of the distal nephron, the vasculature and the renal pel ....Renal dysplasia and renal cystic disease remain significant clinical problems in the paediatric population. Initial animal experiments have demonstrated that inhibiting the renal vasoactive peptide angiotensin during development results in a form of medullary cystic disease. The experiments in this project are aimed at understanding the specific roles and interactions that angiotensin plays in renal development, particularly in development of the distal nephron, the vasculature and the renal pelvis. Importantly the time course of growth and differentiation of these structures varies and the time course of inactivation of angiotensin may result in different malformations. Information from these studies will allow us to understand how clinical problems can arise when angiotensin is absent or other players modify its action. Such situations can arise in humans through sporadic genetic mutations that may well not manifest in widespread clinical abnormalities.Read moreRead less
TARGETING INNATE IMMUNITY THROUGH HMGB1 TO PREVENT DIABETIC NEPHROPATHY
Funder
National Health and Medical Research Council
Funding Amount
$638,581.00
Summary
Diabetes is the leading cause of end stage kidney disease worldwide. As we do not completely understand how diabetes causes kidney failure, we have not been able to design treatments to prevent or cure this disease. The current proposal examines a new target within the immune system HMGB1 that appears likely to cause kidney damage in animals with diabetes. If true, this finding would open up a new series of targets in our search for treatments for diabetic kidney disease.
Progressive Renal And Vascular Disease: Pivotal Role Of The AT2 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$283,875.00
Summary
Diabetes and renal disease are commonly associated with a range of vascular complications. I have been investigating a particular hormone system known as the renin-angiotensin system in promoting kidney and vascular complications in various diseases including diabetes. This system is a pathway which ultimately generates a hormone called angiotensin II which has many actions which could be harmful to the kidney and blood vessels. The importance of this hormone system has been demonstrated by the ....Diabetes and renal disease are commonly associated with a range of vascular complications. I have been investigating a particular hormone system known as the renin-angiotensin system in promoting kidney and vascular complications in various diseases including diabetes. This system is a pathway which ultimately generates a hormone called angiotensin II which has many actions which could be harmful to the kidney and blood vessels. The importance of this hormone system has been demonstrated by the beneficial effects particularly on the kidney of drugs which block this pathway. It has been demonstrated that angiotensin II acts via 2 different receptors, the AT1 and AT2 subtypes. Initially the AT1 receptor was viewed to mediate most of the biological effects of angiotensin II. However, as demonstrated by our own and other groups, the AT2 receptor may play a role in mediating various effects of angiotensin II particularly in disease states. We have identified expression of this receptor in the adult kidney and in the vessel wall which may be upregulated in various disease states. The status of the AT2 receptor is not well characterised in diabetes and many other kidney diseases and this proposal will address this issue in a comprehensive manner by evaluating various sites of injury in diabetes including the kidney and vascular tree. This proporsal includes different approach to moduate this receptor involving drug blockers and animal model where this receptoris either deleted or overexpressed. These studies potentially have major implications for the management of diabetic and renal complications. It remains to be determined if the AT2 receptor confers beneficial or deleterious effects in diabetic nephropathy or other renal diseases, if these effects vary among the various organs to be studied and whether AT2 receptor antagonists may themselves be of therapeutic value in individuals at high risk of kidney and vascular disease such as people with diabetes.Read moreRead less
New Treatments For Acute Kidney Injury-Targeting The IL-17A Pathway
Funder
National Health and Medical Research Council
Funding Amount
$507,200.00
Summary
Acute kidney injury (AKI) is a common cause of ill-health and death. Despite the frequency and seriousness of AKI no new treatments have developed over the past 40 years. While AKI can occur spontaneously it can also develop after treatment with medications, in particular cancer therapies. In this proposal we will explore the effect of new treatments to prevent AKI. We plan to identify new treatments for patients with AKI, with particular relevance to patients receiving cancer treatments.
The Role Of Toll-like Receptors In Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$740,452.00
Summary
Diabetic nephropathy (DN) is the leading cause of chronic kidney disease globally and the No.1 cause of kidney failure requiring dialysis or transplantation in Australia. We are unsure why kidney scarring and failure develops in people with diabetes. Because of this, we have no specific treatments. Our studies suggest an immune receptor present in the kidney may be important. We aim to see whether absence of these receptors can prevent DN, thus identifying a specific target for treatment.
A Novel And Unique Protein I-body For The Treatment Of Chronic Kidney Disease Through Targeting CXCR4
Funder
National Health and Medical Research Council
Funding Amount
$768,340.00
Summary
Chronic kidney disease (CKD) is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease, and premature death. Kidney transplantation and dialysis are the only options for the management of CKD, which results in a significant burden on the health system. The central aim of this project is to develop a novel therapeutic strategy to limit/reverse CKD, which will lead to a researcher-industry partnership in discovery of novel therapeutic agent.
The Role Of Tissue Hypoxia In The Evolution Of Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$509,391.00
Summary
We will determine how low oxygen levels in the kidney lead to kidney disease. We can now measure the levels of oxygen in kidney tissue in rats 24 hours a day, 7 days a week, in a completely non-invasive way. We will study two common kinds of kidney disease. One, acute kidney injury, can result from administration of contrast agents used in x-ray diagnostic procedures. The other, chronic kidney disease, is common in patients with diabetes or high blood pressure.