The Risks Of Thin Basement Membrane Nephropathy (TBMN)
Funder
National Health and Medical Research Council
Funding Amount
$253,500.00
Summary
Our aims are to save the $10 million spent on inappropriate investigations in TBMN each year by the Australian community; to identify and treat individuals with TBMN at risk of renal impairment in order to delay the onset of kidney failure; to understand the underlying disease mechanisms in order to develop specific treatments; and to contribute to the development of a diagnostic assay for TBMN that flags mutations associated with renal impairment and includes a screening test for modifying gene ....Our aims are to save the $10 million spent on inappropriate investigations in TBMN each year by the Australian community; to identify and treat individuals with TBMN at risk of renal impairment in order to delay the onset of kidney failure; to understand the underlying disease mechanisms in order to develop specific treatments; and to contribute to the development of a diagnostic assay for TBMN that flags mutations associated with renal impairment and includes a screening test for modifying genes. The proposed project will change the practice of clinicians by providing evidence for our clinical definition of TBMN and reduce the need for renal biopsies and other investigations thus saving the Australian community up to $10 million annually. demonstrate that a peripheral retinopathy distinguishes between TBMN and X-linked Alport syndrome. This will be a major advance in the diagnosis of Alport syndrome too. determine how often individuals with persistent haematuria who have proteinuria >500 mg-day or renal impairment actually have TBMN. identify the genetic risk factors for renal impairment in TBMN in both the genes directly responsible for TBMN as well as in the modifying genes. determine the mechanisms by which genetic mutations and modifying genes in TBMN cause disease and predispose to renal impairment. Understanding these mechanisms is the first step in the development of specific treatments.Read moreRead less
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
The glomerulus is the filtering component of the kidney. In many diseases, it can be the target of an inappropriate inflammatory response. As part of this response, white blood cells accumulate in the glomerulus where they cause damage. In this project, we make use of special microscopes to examine the glomerulus during an inflammatory response, with the aim of understanding the actions of leukocytes present in glomeruli and how they cause inflammation and damage the glomerulus.