Kidney failure is a devastating consequence of diabetes mellitus. Evidence exists that increased amounts of glucose are filtered by the kidney and then together with salt is reaborbed, in patients with diabetes. The increased glucose and salt reabsorption is considered to trigger cellular damage leading to renal failure. The studies will determine if reducing glucose and salt resportion by the kidney protects against the development of renal failure in models of diabetic renal disease.
Preventing Diabetic Complications Using Anti-inflammatory Peptides
Funder
National Health and Medical Research Council
Funding Amount
$805,146.00
Summary
The Receptor for Advanced Glycation End-products (RAGE) triggers inflammation. It was thought that this receptor was only activated from outside the cell. However, we discovered that other receptors can activate it from the inside. This is called trans-activation. During this ideas grant, we will develop innovative ways to block trans-activation of RAGE and translate these findings to make new therapeutics that are highly-relevant to he development and progression of diabetes.
Understanding The Mechanistic Basis Of Microalbuminuria In Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$613,757.00
Summary
The appearance of small amounts of albumin in the urine (microalbuminuria) in people with diabetes is a marker of progressive kidney disease, while microalbuminuria in the general population is a major risk factor for cardiovascular disease. The reason why microalbuminuria develops is poorly understood. This project will investigate dysfunction of kidney tubular cells as the mechanistic basis of microalbuminuria. If proven, this will provide a new link between kidney and cardiovascular disease.
A Central Role For Carbonic Anhydrase In Renal Hypertrophy And Interstitial Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$414,888.00
Summary
1 in 3 Australians are at risk of developing kidney disease. Renal replacement therapies (dialysis and transplantation) currently cost over $1.2 billion per year. These therapies do not address the underlying cause of the disease. Much research has focused on novel strategies to reverse kidney damage with mixed success. In this project we examine a novel preventative strategy based on currently available therapeutics that may slow the progression of kidney disease.
Does Excess Consumption Of Dietary Advanced Glycation End Products Activate The Complement Pathway Contributing To Diabetic Nephropathy?
Funder
National Health and Medical Research Council
Funding Amount
$470,617.00
Summary
Modern lifestyle is characterised by the consumption of foods that have been highly processed to improve their shelf life and flavour. However, this food processing has been shown to generate potentially harmful compounds, Advanced Glycation End Products (AGEs) that may promote inflammation and worsen diabetic kidney disease. This study investigates the effects of overeating a diet high in AGEs on the function of the kidney, and aims to find out how these AGEs lead to kidney damage.
We have validated CDA1 as an effective target to retard kidney disease in diabetes using a mouse model where we deleted the CDA1gene. We have also developed a novel agent to inhibit CDA1 in order to retard diabetic kidney disease. In this application, we propose to confirm the efficacy of targeting CDA1 using various diabetes models and a range of strategies to target CDA1. We will also rigorously explore translation of these findings to a new treatment for diabetic renal disease.
TARGETING INNATE IMMUNITY THROUGH HMGB1 TO PREVENT DIABETIC NEPHROPATHY
Funder
National Health and Medical Research Council
Funding Amount
$638,581.00
Summary
Diabetes is the leading cause of end stage kidney disease worldwide. As we do not completely understand how diabetes causes kidney failure, we have not been able to design treatments to prevent or cure this disease. The current proposal examines a new target within the immune system HMGB1 that appears likely to cause kidney damage in animals with diabetes. If true, this finding would open up a new series of targets in our search for treatments for diabetic kidney disease.
Role Of Growth And Transcription Factors In Tubulointerstitial Injury In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$454,023.00
Summary
Progressive kidney disease occurs as a result of a range of molecular and cellular pathways. One of the commonest causes of kidney disease is diabetes and this appears to be partly related to increased expression and action of certain growth factors such as CTGF. These factors promote the deposition of scar tissue in the kidney and one of the ways these promote this scarring is to change a cell s behaviour so that it now lays down collagen. This proposal will not only focus on how CTGF promotes ....Progressive kidney disease occurs as a result of a range of molecular and cellular pathways. One of the commonest causes of kidney disease is diabetes and this appears to be partly related to increased expression and action of certain growth factors such as CTGF. These factors promote the deposition of scar tissue in the kidney and one of the ways these promote this scarring is to change a cell s behaviour so that it now lays down collagen. This proposal will not only focus on how CTGF promotes scarring but will explore 2 novel factors called Snail and Slug which can act directly on particular genes such as CTGF to inhibit these deleterious effects. By further characterising these pathways involving Snail, Slug and CTGF in the kidney it will be possible to generate new targets and therapies for various forms of progressive kidney disease including diabetic kidney disease.Read moreRead less
Cell Type Specific Mechanisms Of Mineralocorticoid Mediated Renal Injury In Glomerulonephritis And Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$103,582.00
Summary
Mineralocorticoid exists normally in the human body to maintain fluid and salt balance. However, it is also implicated in diseases affecting the heart and the kidneys. My research aims to further our understanding on how mineralocorticoids contribute to kidney disease, and in particular, to investigate the role of specific kidney cells on mediating kidney injury. Ultimately this research may facilitate development of treatments allowing cell specific blockade of mineralocorticoids, which may red ....Mineralocorticoid exists normally in the human body to maintain fluid and salt balance. However, it is also implicated in diseases affecting the heart and the kidneys. My research aims to further our understanding on how mineralocorticoids contribute to kidney disease, and in particular, to investigate the role of specific kidney cells on mediating kidney injury. Ultimately this research may facilitate development of treatments allowing cell specific blockade of mineralocorticoids, which may reduce kidney diseases such as diabetic nephropathy.Read moreRead less
Investigating Pathways Of Mitochondrial Quality Control In Diabetic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$944,518.00
Summary
The mitochondria, the “power plants” of the cell, are damaged and accumulate in the kidney in diabetes. The objective of this study is to investigate exactly how these dysfunctional mitochondria accumulate in the diabetic kidney. The ultimate aim of this study is to establish if mitochondrial health can be restored using new medicines that directly target mitochondria, which will then improve kidney function, leading to new therapies for people with diabetes.