Molecular Mechanisms Of Macrophage-mediated Renal Injury.
Funder
National Health and Medical Research Council
Funding Amount
$437,036.00
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 have only limited efficacy and are associated with significant side-effects. Therefore, we need to understanding the way in which the kidney is damaged in disease in order to identify new and specific approaches to the tr ....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 have only limited efficacy and are associated with significant side-effects. Therefore, we need to understanding the way in which the kidney is damaged in disease in order to identify new and specific approaches to the treatment of kidney 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, on 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 can be a starting point for the development of new and specific approaches to the treatment of human kidney disease.Read moreRead less
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
Human Podocyte Depletion, Glomerular Hypertrophy And Glomerulosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$601,490.00
Summary
Many kidney diseases commence with injury to glomeruli (kidney filters) which leads to glomerular scarring and loss. There is strong evidence from animal studies that a specific glomerular cell type (the podocyte) is central to this process of glomerular injury. In this study, we will analyse the relationships between podocyte depletion and glomerular scarring in human kidneys from 5 racial groups (white and African Americans, white and Aboriginal Australians, Senegalese Africans).
Kidney disease occurs in up to 50% of patients with insulin-dependent (type 1) and non-insulin-dependent (type 2) diabetes. The increasing rate of diabetes in our community has made it a major cause of kidney disease and a growing health problem. Despite clinical attempts to control blood glucose and blood pressure levels, kidney disease in most diabetic patients progresses towards a complete loss of kidney function. In severe cases, the survival of the patient is dependent upon lifelong dialysi ....Kidney disease occurs in up to 50% of patients with insulin-dependent (type 1) and non-insulin-dependent (type 2) diabetes. The increasing rate of diabetes in our community has made it a major cause of kidney disease and a growing health problem. Despite clinical attempts to control blood glucose and blood pressure levels, kidney disease in most diabetic patients progresses towards a complete loss of kidney function. In severe cases, the survival of the patient is dependent upon lifelong dialysis or transplantation, which are costly and complicated treatments. Therefore, there is an urgent need to improve treatment stategies in diabetic patients to avoid kidney failure. Recent evidence in human and experimental models of diabetic kidney disease has indicated that macrophages infiltrate the kidney during the disease process. Our previous knowledge from other inflammatory kidney diseases suggests that macrophages play an important role in promoting the progression of disease and, in some of these diseases, treatment strategies which block macrophage function and accumulation have been shown to be effective in inhibiting the disease. The overall aim of these studies will be to determine the importance of macrophages in the pathogenesis of diabetic kidney disease and identify the mechanisms regulating their recruitment and activation within the diabetic kidney. This will be achieved by examining the progression of kidney disease in type 1 and type 2 diabetic mice which have been genetically modified to prevent macrophage accumulation and activation within the kidney. These studies will provide valuable information into the pathogenesis of diabetic kidney disease and will identify whether therapeutic strategies targeting macrophages can help prevent kidney loss in diabetes.Read moreRead less