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).
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
New Insights Into The Role Of Renal Endothelial Dysfunction In The Pathogenesis Of Glomerular Injury And Renal Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$577,722.00
Summary
This project will ascertain whether abnormal function of endothelial cells contribute to diabetic and non-diabetic kidney diseases, the leading cause of end-stage kidney disease. The outcome of this study will allow us to reevaluate the role of endothelial cells in kidney scarring, lead us to question our current approaches to the treatment and management of chronic kidney disease and eventually may be helpful for the design of novel therapies to treat chronic kidney diseases.
New Roles For The Spleen Tyrosine Kinase In Antibody-independent Renal Injury.
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
This study investigates the novel hypothesis that a particular cell activation pathway (called Syk) is important not only in antibody-based kidney disease, but that it also plays a previously unrecognised role in other forms of antibody-independent kidney disease. Drugs that inhibit the Syk pathway are in clinical development for treatment of diseases such as arthritis. Hence, a positive outcome of this project could lead to the use of Syk inhibitors in many different types of kidney disease.
Resolvin E1 Is A Novel Anti-inflammatory And Anti-fibrotic Lipid Mediator For The Treatment Of Chronic Kidney Disease.
Funder
National Health and Medical Research Council
Funding Amount
$519,246.00
Summary
This project will ascertain whether a naturally occurring compound, Resolvin E1 with potent anti-inflammatory properties, can effectively halt the progression of experimental kidney disease. We will also test whether Resolvin E1 can exert other potential benefits in suppressing progressive fibrosis of the kidney. The outcome of this study will allow us to evaluate the therapeutical potential of Resolvin E1 for the treatment of acute and chronic kidney diseases.
Distinct Pathogenic Roles For JNK Signalling In Glomerular And Interstitial Injury In Kidney Disease.
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
Our studies have identified a stress-activated mechanism (the JNK signalling pathway) as a therapeutic target in the treatment of kidney disease. The current project will define the role of JNK signaling in individual cell types in the development of different types of kidney disease. These studies will provide new insights into the pathogenesis of kidney disease, and will be highly relevant to other diseases, including atherosclerosis, lung fibrosis and arthritis.