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Neural Control Of Renal Function: Functionally Specific Populations Of Sympathetic Nerves
Funder
National Health and Medical Research Council
Funding Amount
$286,250.00
Summary
The kidneys are supplied with a dense network of nerves. Working properly, these nerves help maintain normal filtering of the blood by the kidneys. Over-activity of the nerves going to the kidney is associated with congestive heart failure, liver cirrhosis, chronic renal failure and hypertension. We have recently made several major discoveries about these nerves. Our studies suggest, based on structural and functional evidence, that stimulation of subgroups of nerve fibers going to the kidney wi ....The kidneys are supplied with a dense network of nerves. Working properly, these nerves help maintain normal filtering of the blood by the kidneys. Over-activity of the nerves going to the kidney is associated with congestive heart failure, liver cirrhosis, chronic renal failure and hypertension. We have recently made several major discoveries about these nerves. Our studies suggest, based on structural and functional evidence, that stimulation of subgroups of nerve fibers going to the kidney will causes different effects with in the kidney . We therefore suggest that salt excretion , the control of blood flow to the kidney and the release of hormones by the kidney can be seperately regulated by the nerves. Using techinques only practise in a handful of laboratories around the world, we aim to determine to how the nerves control kidney function normally. These studies will suggest new directions in which the renal nerves may be implicated in disease.Read moreRead less
I am a cardiovascular physiologist investigating the origin of the large increases in cardiac and renal sympathetic nerve activity in heart failure,the causes of acute renal failure in septic shock and mechanisms to reduce myocardial ischaemia-reperfusion
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.
Tubulointerstitial Epigenetics- The Underlying Basis Of Progressive Fibrosis In Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$378,940.00
Summary
Although the kidney has capacity to repair after mild injuries, ongoing or severe injury results in scarring (so-called fibrosis) and a progressive loss of kidney function. Understanding the mechanisms that regulate the transition from repair to fibrosis is important, because once fibrosis is initiated it can be extremely difficult to switch off or reverse.
Body Composition Changes In Cardiac Cachexia: Pathophysiology, Quantification And Approaches To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$120,000.00
Summary
Cachexia is weight loss and weakness caused by disease, or as a side effect of illness. Congestive heart failure is a common cardiovascular condition that is accompanied by high mortality (up to 50% over 2 years) and considerable suffering. People with congestive heart failure often develop cachexia. This project will explore the mechanisms responsible for the development of cachexia using an animal model of cardiac cachexia that the researchers have developed. It will be complemented by an exam ....Cachexia is weight loss and weakness caused by disease, or as a side effect of illness. Congestive heart failure is a common cardiovascular condition that is accompanied by high mortality (up to 50% over 2 years) and considerable suffering. People with congestive heart failure often develop cachexia. This project will explore the mechanisms responsible for the development of cachexia using an animal model of cardiac cachexia that the researchers have developed. It will be complemented by an examination of the effects of exercise on measures of cachexia in patients with congestive heart failure. The researchers believe that this study will supply valuable new information about the development of cachexia and lead to new therapies for this syndrome.Read moreRead less
Development Of Oral Natriuretic-like Peptides For Chronic Treatment Of Congestive Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$389,533.00
Summary
Congestive heart failure is fatal disease and a major disease burdon for the community affecting nearly half a million Australians.. Current therapies are inadequate and very limited in prolonging life. We seek to develop a new peptide therepy based on the effectivness of human B type natriuetic peptide which has to be given by injection. Our aim is to produce an orally active and effective treatment based on peptides discovered in snake venom. The program involves testing in animals and cells
Sympathetic Nervous System Activation In Renal Failure. Its Contribution To Pathogenesis And Progression.
Funder
National Health and Medical Research Council
Funding Amount
$490,796.00
Summary
Cardiovascular morbidity and mortality is exceedingly high in patients with chronic renal failure and particularly end stage renal disease. Recent studies suggest that sympathetic activation contributes substantially to the development of hypertension, progression of renal disease and cardiovascular prognosis in these patients. Increased sympathetic nerve firing has been demonstrated in end stage renal disease by the use of clinical microneurography, which has been attributed to uremia-related t ....Cardiovascular morbidity and mortality is exceedingly high in patients with chronic renal failure and particularly end stage renal disease. Recent studies suggest that sympathetic activation contributes substantially to the development of hypertension, progression of renal disease and cardiovascular prognosis in these patients. Increased sympathetic nerve firing has been demonstrated in end stage renal disease by the use of clinical microneurography, which has been attributed to uremia-related toxins. However, renal transplant recipients with excellent graft function and no signs of uremia still exhibit increased sympathetic nerve firing. Most interestingly, bilateral nephrectomized patients have nerve firing rates comparable to that of normal control subjects without renal disease. These data suggest that the diseased kidneys exert excitatory effects on the sympathetic nervous system independent of correction of uremia. The proposed study aims to comprehensively investigate the pattern of sympathetic activation both centrally (microneurography) and regionally (radiotracer dilution methodology) in patients with chronic renal failure and end stage renal disease . The effect of the centrally acting sympatholytic drug rilmenidine on sympathetic activity in the setting of renal disease will be assessed. Patients with ESRD waitlisted for kidney transplantation will be studied before and after transplantation. Some of the transplant recipients will also have undergone uni- or bilateral nephrectomy before transplantation which will enable us to further explore the role of the diseased kidneys in sympathetic activation. The results of this study may prove to have significant implications for treatment and prevention of cardiovascular morbid events frequently associated with renal disease.Read moreRead less
Long Term Sequelae Of Acute Kidney Injury: Identifying The Optimal Model Of Care And Intervention To Enhance Patient Outcome
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Acute kidney injury (AKI) is associated with significant morbidity, mortality and health care costs. It is increasingly recognised as a key driver of progressive kidney disease, and no intervention has been shown to improve the long-term outcome of AKI survivors. This project identifies risk factors for chronic kidney disease, dialysis dependence and death after an episode of AKI, and examines the feasibility, efficacy, and cost-effectiveness of early nephrology review in high risk individuals.
Catheter Based Renal Denervation To Improve Outcomes In Congestive Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$619,194.00
Summary
In heart failure there is a large increase in sympathetic nerve activity that is detrimental to patient outcome, but the factors causing this increased activity are not well defined. There is evidence that renal nerves play a significant role. A novel catheter based technique allows silencing of these nerves. We will test whether this novel technique has the potential to improve the outcomes for patients with heart failure.
Electrophysiologic Phenotyping Of Non Ischaemic Cardiomyopathy To Predict Clinical Outcome
Funder
National Health and Medical Research Council
Funding Amount
$374,676.00
Summary
Non-ischemic cardiomyopathy (NICM) is a common cause of heart failure and sudden death. Currently, the guidelines for the management are generalised and do not differentiate patients at high risk of disease progression and sudden death. This project aims to identify the electrical and structural properties of heart, to predict the clinical course in patients with NICM. Identification of high-risk patients will help allocate resources wisely and enable appropriate patient counselling.