Mechanisms Of Infection Triggered Renal Vasculitis
Funder
National Health and Medical Research Council
Funding Amount
$413,900.00
Summary
Kidney disease, including glomerulonephritis, is an important cause of ill-health in Australia. Some forms of kidney inflammation are linked to infection, but we don�t understand why. This project explores products from bacteria, particularly S.aureus, to work out how bacterial infection affects a form of kidney inflammation - ANCA-associated glomerulonephritis. It will establish how infection related signals activate local and immune cells, and define links between infection and the disease.
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.
Role Of The Lysosomal Protein SCARB2 In Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$475,658.00
Summary
Loss of protein in the urine is one of the most important things that happens before the kidneys fail. Losing protein seems to damage the kidneys, but we are still not sure how it happens in most people. We are studying the 'waste management system' of cells, that enables them to get rid of proteins that are no longer required. We have some evidence that this system is abnormal in inherited proteinuria and now want to find out if this is also a problem in more common diseases.
Kidney failure is a major health disorder in Australia and with more diabetes the number of patients waiting for transplant on dialysis is increasing. Current treatments give good initial survival of the kidney transplant but most kidneys are lost due to chronic damage . We propose a number of tolerance strategies in a model of kidney transplantation that will allow transplantation without longterm immunosuppression.
To investigate alternative strategies to treat end stage renal disease we have transplanted embryonic kidneys into the wall of the abdominal cavity of adult hosts where they become vascularised and undergo continued but limited development. Strategies to enhance their growth-development and decrease immunogenicity-rejection will now be determined, and the origin of a 'ureter-like' tube of tissue that grows to connect the transplanted embryonic kidney with the recipient bladder investigated.
Regulation Of SPAK By AMPK Links Salt Reabsorption To Energy Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
Excessive salt and energy intake have emerged as major features of the unhealthy fast-food culture. Salt promotes high blood pressure, whereas high energy intakes increase obesity and diabetes. In this study, we aim to determine how energy availability and salt handling are linked in the kidney. This research will lead to new ways to treat high blood pressure by limiting salt reabsorption in the kidney.
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.
Renal Medullary Blood Flow: Regulation By Paracrine, Endocrine And Neural Factors
Funder
National Health and Medical Research Council
Funding Amount
$410,616.00
Summary
High blood pressure is a condition afflicting more than 10% of our community, and is the leading risk factor for stroke and heart disease. The kidneys play a critical role in control of blood pressure under normal conditions, and probably also in the initiation and maintenance of high blood pressure. This influence is exerted both through the excretion of salt and water, and by the release of substances into the circulation that affect blood pressure (hormones). Recent experiments performed by u ....High blood pressure is a condition afflicting more than 10% of our community, and is the leading risk factor for stroke and heart disease. The kidneys play a critical role in control of blood pressure under normal conditions, and probably also in the initiation and maintenance of high blood pressure. This influence is exerted both through the excretion of salt and water, and by the release of substances into the circulation that affect blood pressure (hormones). Recent experiments performed by us and others have indicated that the inner part of the kidney (the medulla) is critical in these functions, which appear to be regulated by the level of blood flow in the medulla of the kidney. Our recent experiments also show that hormones and nerves have diverse effects on blood flow in the different regions of the kidney, showing that these factors can differentially affect blood pressure depending on their effects on medullary blood flow. Importantly, these hormones and nerves do not act in isolation, but act in concert, and in association with so called 'second messenger' systems that act locally to directly affect the contraction of muscle in blood vessels, and so blood vessel size. The experiments described in this application are aimed at determining how circulating and locally acting hormones, and the nerves in the kidney, interact together to control blood flow in the different regions of the kidney. This will help us understand how blood flow to the medulla of the kidney is regulated normally, so that we can begin to understand how malfunction of these systems can contribute to the development of high blood pressure.Read moreRead less
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.
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.