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.
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.
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.
Risks Of Using A Central Venous Catheter For Haemodialysis In Australia And Opportunities For Improvement
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Patients with permanent or temporary severe kidney failure require dialysis treatment to remain alive and well. Commonly this is performed using a catheter (plastic tube) inserted into a large vein of the body. The use of these catheters, while life saving, is prone to complications. By assessing health data from multiple sources, this project will provide an understanding of the frequency and risk factors for such complications, and improve the lives of patients requiring such treatment.
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
Extended Follow Up Of The RENAL Study And Individual Patient Data Meta-analysis In Acute Kidney Injury
Funder
National Health and Medical Research Council
Funding Amount
$650,271.00
Summary
Acute kidney failure is increasingly common and associated with very high mortality. The long term consequences for patients and their kidney function are unknown. By extending follow up of the RENAL study, which explored how the dose of dialysis affected survival, and combining it with other trials from around the world, we will provide the strongest evidence regarding how dialysis treatment can reduce this mortality and define the long term consequences of this condition.
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
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.
The Role Of Tissue Factor In Renal Ischaemia-Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$268,500.00
Summary
Reestablishment of blood flow to an organ (reperfusion) following temporary cessation or obstruction is essential for survival and recovery of the organ. However while essential for organ survival reperfusion results in damage to the organ in a number of cases, including heart, brain, kidney, and gastrointestinal tract, with important implications for patient morbidity and mortality. In the kidney lack of blood flow can result in acute kidney failure that is a costly condition to manage often re ....Reestablishment of blood flow to an organ (reperfusion) following temporary cessation or obstruction is essential for survival and recovery of the organ. However while essential for organ survival reperfusion results in damage to the organ in a number of cases, including heart, brain, kidney, and gastrointestinal tract, with important implications for patient morbidity and mortality. In the kidney lack of blood flow can result in acute kidney failure that is a costly condition to manage often requiring admission to an intensive care unit and is still associated with a significant risk of death. Reperfusion injury that occurs during renal transplantation is currently thought to be an important contributor to delayed establishment of kidney function following transplantation that in turn may increase the incidence of acute and chronic rejection. The studies outlined in this proposal will investigate how molecules involved in the blood clotting system may contribute to the inflammatory response that occurs upon reperfusion of the kidney following prior obstruction of blood flow. We will study a mouse model of kidney reperfusion injury and using genetically modified mice determine the role of various blood clotting-related proteins in subsequent inflammation and organ damage. The approach to be employed will provide a powerful method to determine the role of various molecules and pathways in contributing to kidney damage after reperfusion injury. Interventions that may reduce the incidence or severity of renal damage following kidney reperfusion injury have the potential to be of major benefit to patients and to reduce health care costs.Read moreRead less