RCT Of Aspirin And Fish Oil For The Prevention Of Thrombosis In Arterio-venous Fistulae For Dialysis Access
Funder
National Health and Medical Research Council
Funding Amount
$1,869,190.00
Summary
This randomised, placebo-controlled clinical trial aims to determine whether the anti-platelet agents aspirin and fish oil, either alone or in combination, will effectively reduce the risk of early thrombosis (blood clots) in arterio-venous fistulae (AVF) that are used for accessing the circulatory system in dialysis. The trial is to be conducted by the Australasian Kidney Trials Network (AKTN). 1200 patients requiring haemodialysis who are scheduled to undergo creation of an AVF and are not cur ....This randomised, placebo-controlled clinical trial aims to determine whether the anti-platelet agents aspirin and fish oil, either alone or in combination, will effectively reduce the risk of early thrombosis (blood clots) in arterio-venous fistulae (AVF) that are used for accessing the circulatory system in dialysis. The trial is to be conducted by the Australasian Kidney Trials Network (AKTN). 1200 patients requiring haemodialysis who are scheduled to undergo creation of an AVF and are not currently taking anti-platelet agents will be recruited over 3 years. AVF is the accepted standard for haemodialysis patients because it utilises the patient's own artery and vein to allow repeated access to the vascular system with a minimal risk of complications. Failure of the AVF means the use of inferior permanent venous catheters or arterio-venous artificial grafts. These devices are more costly to insert, and have an increased risk of failure due to infection and thrombosis. Reducing this rate of failure by simple, cheap and readily available interventions has the potential to reduce these problems. Aspirin has been chosen because of its well-established anti-thrombosis effects. Fish oil has a number of biological effects which make it an attractive agent for the prevention of vascular access thrombosis. Study treatment will be aspirin 100 mg per day or matching placebo, and fish oil 4 gm daily or matching placebo, both commencing on the day prior to surgery and continued for 3 months. If the trial demonstrates a positive effect of either or both agents, this will lead to a reduction in thromboses, quicker time to working dialysis access, and less need for surgery.Read moreRead less
To Improve The Accuracy And Precision Of Estimated GRF (eGFR) Measurements In Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$959,349.00
Summary
There is an overwhelming burden of chronic disease in Indigenous Australians. In order to attempt to improve kidney disease in this high-risk population, it is vital that we are able to accurately measure kidney function. This study will provide evidence to accurately assess kidney function in Indigenous Australians. This will then enable development of appropriate clinical guidelines and more effective monitoring of future interventions to slow progression of kidney disease.
DNA Vaccination Using Chemokine And Costimulatory Pathways As A Treatment For Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$450,390.00
Summary
Chronic kidney disease (CKD) is a great burden on Australia. Treatments are mostly ineffective. Our DNA vaccination against mediators of inflammation can protect against CKD. On the basis of ongoing studies we have identified 5 candidate molecules involved in recruitment and activation of inflammatory cells. We outline studies to generate DNA vaccines to these molecules, enhance their efficacy, and test them in models that represent the 3 most important causes of human CKD.
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.
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
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.
Targeting Innate Immunity To Prevent Chronic Dysfunction Of The Transplanted Kidney
Funder
National Health and Medical Research Council
Funding Amount
$497,057.00
Summary
Kidney transplantation is the optimal treatment for patients suffering from end-stage kidney disease. Chronic transplant dysfunction is the major barrier to long-term health after transplantation, and is the subject of this application. Our studies suggest a signaling system activates immunity and leads to chronic transplant dysfunction. We aim to block this signaling system in mouse models to identify clinically applicable treatments to prevent kidney transplant failure.
Normoalbuminuric And Albuminuric Pathways To Renal Insufficiency In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$288,900.00
Summary
Up to one third of patients with type 2 diabetes develop kidney disease (diabetic nephropathy). An increase in protein excretion in the urine (albuminuria) is usually the first sign of kidney disease. Albuminuria usually progresses from normal levels to an intermediate phase (microalbuminuria) lasting 5-10 years and is then followed by overt nephropathy (macroalbuminuria). It has been traditionally believed that onset of a decline in kidney function, measured as glomerular filtration rate, accom ....Up to one third of patients with type 2 diabetes develop kidney disease (diabetic nephropathy). An increase in protein excretion in the urine (albuminuria) is usually the first sign of kidney disease. Albuminuria usually progresses from normal levels to an intermediate phase (microalbuminuria) lasting 5-10 years and is then followed by overt nephropathy (macroalbuminuria). It has been traditionally believed that onset of a decline in kidney function, measured as glomerular filtration rate, accompanies the development of diabetic kidney disease. However, recent studies by our group have shown that about one quarter of patients with type 2 diabetes have impaired kidney function without an increase in albuminuria. This raises the possibility that an alternate non-albuminuric pathway leads to kidney disease in a subgroup of patients with type 2 diabetes. This study will compare kidney structure and function in patients with type 2 diabetes and impaired kidney function with or without increases in albuminuria. The comparison will be accompanied by measurements of the rate of decline in kidney function over 5 years or more, in subjects with or without increases in albuminuria in order to confirm that kidney function may decline independently of albuminuria. The demonstration of alternate mechanisms of renal injury has the potential to identify new targets for the treatment of kidney disease in patients with type 2 diabetes.Read moreRead less
Role Of Vasoactive Hormones And Cytokines In Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$361,650.00
Summary
Kidney disease is a major cause of disability and premature death in the Australian population. In diabetic kidney disease a major factor which accelerates the progression of this disorder is the presence of hypertension. Indeed international and national organisations now recommend aggressive blood pressure treatment in the diabetic patient. This proposal aims to optimise blood pressure treatment in diabetes and evaluate novel more potent blood pressure lowering agents which block within the ki ....Kidney disease is a major cause of disability and premature death in the Australian population. In diabetic kidney disease a major factor which accelerates the progression of this disorder is the presence of hypertension. Indeed international and national organisations now recommend aggressive blood pressure treatment in the diabetic patient. This proposal aims to optimise blood pressure treatment in diabetes and evaluate novel more potent blood pressure lowering agents which block within the kidney important hormonal pathways implicated in diabetic kidney disease. This approach will assist in determining key factors which mediate the damage to the kidney induced by elevated blood pressure. It is anticipated that these studies will lead to more rational, targeted and powerful antihypertensive agents which will retard or prevent the development of diabetic nephropathy.Read moreRead less