AMP-activated Protein Kinase (AMPK) In Acute Renal Failure
Funder
National Health and Medical Research Council
Funding Amount
$401,523.00
Summary
Acute renal failure is a common complication of any severe illness. Generally, it is the lack of blood flow, or food that leads to this problem. People who are ill are unable to provide adequate blood flow to their kidneys, so the kidneys become diseased and fail to function. This can be fatal. There are, however, mechanisms in the kidney that are designed to avoid this shortage of energy. The aim of these studies is to find out what these protective mechanisms usually do in the kidney, and unde ....Acute renal failure is a common complication of any severe illness. Generally, it is the lack of blood flow, or food that leads to this problem. People who are ill are unable to provide adequate blood flow to their kidneys, so the kidneys become diseased and fail to function. This can be fatal. There are, however, mechanisms in the kidney that are designed to avoid this shortage of energy. The aim of these studies is to find out what these protective mechanisms usually do in the kidney, and understand why they are not more active. We hope to find ways to switch them on earleir, using drugs, so as to protect the kidneys from injury.Read moreRead less
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.
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.
I am a nephrologist, clinical epidemiologist and health services researcher aiming to generate high-quality evidence regarding the prevention and management of chronic disease and to reduce disparities in indigenous health.
Long Term Sequelae Of Acute Kidney Injury: Identifying The Optimal Model Of Care And Intervention To Enhance Patient Outcome
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Acute kidney injury (AKI) is associated with significant morbidity, mortality and health care costs. It is increasingly recognised as a key driver of progressive kidney disease, and no intervention has been shown to improve the long-term outcome of AKI survivors. This project identifies risk factors for chronic kidney disease, dialysis dependence and death after an episode of AKI, and examines the feasibility, efficacy, and cost-effectiveness of early nephrology review in high risk individuals.
Nephro-protective Effects Of L-amino Acids In Critically Ill Patients: A Multi-centre Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$863,209.00
Summary
More than 60,000 Australians become critically ill each year with up to one third of these patients developing Acute Kidney Injury during their illness. Acute Kidney Injury leads to longer recovery times, may require lifelong dialysis and results in a significantly increased chance of dying as a result of the original critical illness. The purpose of this clinical trial is to determine if a simple and cheap amino acid infusion can reduce the onset of Acute Kidney Injury during critical illness.
Negative Modulators Of Leucocyte Recruitment In The Kidney. The Role Of Slit And Robo.
Funder
National Health and Medical Research Council
Funding Amount
$368,100.00
Summary
Kidney failure is a major health problem in our community, affecting the lives of several thousand individuals and their families. Every year in Australia, about 2,000 new individuals commence dialysis and require ongoing treatment for the rest of their lives. The significant negative impact kidney failure has on quality of life and on life expectancy added to the major shortage of transplant organs, makes the development of effective therapies for kidney diseases an important goal. Our current ....Kidney failure is a major health problem in our community, affecting the lives of several thousand individuals and their families. Every year in Australia, about 2,000 new individuals commence dialysis and require ongoing treatment for the rest of their lives. The significant negative impact kidney failure has on quality of life and on life expectancy added to the major shortage of transplant organs, makes the development of effective therapies for kidney diseases an important goal. Our current therapies have major limitations in terms of their effectiveness and side effects. New therapies which can prevent the progression of kidney disease or prolong the survival of transplanted kidneys may, therefore, have enormous benefits. In order for this to occur, an improved understanding of the common factors underlying kidney disease is required. Our recent studies have been examining the factors influencing kidney inflammation. This process is a significant cause of long term damage in various kidney diseases and in kidney transplants. Our work has identified a potentially major role for recently discovered molecules known as Slit proteins in preventing or decreasing inflammation in the kidney. The level of expression of these molecules in the kidney appears to be rapidly decreased in kidney inflammation and their protective effect is then lost. This imbalance appears to promote the disease process and may be a useful target for the treatment of certain kidney diseases. Our work has found that Slit proteins are able to decrease the movement of white cells (the cells which cause inflammation) out of the blood circulation and into the kidney. The proposed studies aim to better understand the role of these molecules in the kidney as naturally expressed anti-inflammatory agents and to test their potential as therapeutic agents. We hope that the information obtained from these studies will help in the development of new therapies to manage various forms of kidney disease.Read moreRead less
Selective Targeting Of Acute Renal Injury By Inhibition Of The Receptor Tyrosine Kinase, C-fms.
Funder
National Health and Medical Research Council
Funding Amount
$443,007.00
Summary
The progression of kidney disease to end-stage renal failure is a major health problem in our community. We have identified that macrophages, a type of white blood cell, plays an important role in causing inflammatory kidney injury. This project will use clinically relevant animal models to test the therapeutic potential of our new approach to selectively remove these cells from the inflamed kidney and thereby protect it from injury.
Interplay Between Innate And Adaptive Immunity In Kidney Allograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$403,101.00
Summary
Acute allograft rejection (AR) still occurs in up to 40% of patients and is the major cause of graft loss during the first year after kidney transplantation. Even when treated, AR causes graft damage and is a major risk factor for premature graft loss due to chronic allograft nephropathy. Graft loss due to rejection returns the patient to dialysis and thus incurs medical costs in excess of $50,000 p.a. and reduces the duration and quality of life of the patient. Thus, AR directly and indirectly ....Acute allograft rejection (AR) still occurs in up to 40% of patients and is the major cause of graft loss during the first year after kidney transplantation. Even when treated, AR causes graft damage and is a major risk factor for premature graft loss due to chronic allograft nephropathy. Graft loss due to rejection returns the patient to dialysis and thus incurs medical costs in excess of $50,000 p.a. and reduces the duration and quality of life of the patient. Thus, AR directly and indirectly places a major burden upon patients, transplant services and the Australian community. AR occurs because of an adaptive alloimmune response mediated by T cells. The allografts also elicit an innate response and recent work has demonstrated both the prominence of the innate response and its essential role in facilitating adaptive alloimmunity. T cells are a component of the adaptive response and are prominent within rejecting allografts. NKG2D and toll like receptors (TLRs) are components of innate immune system. Our data demonstrates that ischemia reperfusion injury (IRI) causes upregulation of NKG2D ligand RAE-1 by kidney cells and TLR4 expression in kidney IRI and AR and that NKG2D expression is upregulated during kidney AR, and is expressed by intragraft CD8+ cells. Our results indicate that an interaction between innate and adaptive immunity may promote AR. We aim to determine whether: 1) TLR4 is required for the development of IRI to kidney and RAE-1 expression. 2) blockade of the interaction between NKG2D and its ligand RAE-1 expressed on the graft can attenuate AR and consequently prolong graft survival. 3) combined blockade of innate plus adaptive co-stimulatory molecules is more effective than either alone. This work will dissect the key interactions between innate and adaptive immunity in the allograft response and identify new targets for the prevention and treatment of allograft rejection.Read moreRead less