Defining The Central Role Of Podocyte Depletion In The Development, Progression And Management Of Glomerular Disease
Funder
National Health and Medical Research Council
Funding Amount
$690,855.00
Summary
Podocytes are key cellular components of the kidney’s filtration barrier. Podocyte depletion (cell loss or injury) is a key event in most forms of kidney disease. We will investigate interactions between podocyte depletion and two major risk factors for kidney disease (diabetes and hypertension), assess whether podocyte depletion influences therapeutic outcomes, and commence efforts to develop podocyte-specific therapies.
Renal Denervation To Improve Outcomes In Patients With End-stage Renal Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,028,558.00
Summary
End stage renal disease is associated with excess cardiovascular morbidity and mortality. Activation of sympathetic nerves plays an important role in this scenario. We have pioneered a novel catheter-based approach using radiofrequency-energy to disrupt these nerves and we now aim to assess the mechanisms and consequences of applying this novel technology in patients with end-stage renal disease.
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.
Evaluation Of The Efficacy And Safety Of Health Service Dialysate Sodium Practice On Clinical Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$1,958,205.00
Summary
Concerns the delivery of haemodialysis may be contributing to sodium retention and poor outcomes has led many health services to modify practice. However this modification is occurring in an unmeasured and haphazard manner leaving the impact unknown. This simple, pragmatic research will generate definitive evidence on the effect of health service dialysate sodium practices on the key clinical outcomes of death and cardiovascular events as well as health service utilisation.
Mechanisms And Consequences Of Renal Denervation In Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,289,105.00
Summary
Chronic kidney disease (CKD) affects ~10-12% of the adult population and is associated with increased mortality. Activation of sympathetic nerves plays an important role in this scenario. We have pioneered a novel catheter-based approach using radiofrequency-energy to disrupt these nerves and we now aim to assess the mechanisms and consequences of applying this novel technology in patients with chronic kidney disease.
Evidence For Interventions That Improve Cardiovascular Outcomes In Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$421,747.00
Summary
The many Australians with kidney disease experience higher rates of cardiovascular events. Some of the highest rates of cardiovascular events and mortality are seen in people with kidney failure. Currently available treatments are inadequate at reducing this risk indicating an urgent need for new therapies. The program will investigate the effect of little used but readily available, promising interventions to assess their potential to reduce cardiovascular events for people with kidney disease.
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).
The ClC-5 Cl- Channel, A Key Regulatory Role In Albumin Uptake By The Proximal Tubule
Funder
National Health and Medical Research Council
Funding Amount
$510,500.00
Summary
The clinical association between protein loss in the urine and retention of salt, resulting in high blood pressure and progressive decline in kidney function, is well known. Under normal conditions, the kidneys filter 180 litres of water and reabsorb 1.7 kg of salt per day, a function which is principally performed by the kidney tubules in the kidney. Similarly the kidney tubule cells reabsorb and break down up to 3 grams of albumin per day. In the past, it has been considered that excessive pro ....The clinical association between protein loss in the urine and retention of salt, resulting in high blood pressure and progressive decline in kidney function, is well known. Under normal conditions, the kidneys filter 180 litres of water and reabsorb 1.7 kg of salt per day, a function which is principally performed by the kidney tubules in the kidney. Similarly the kidney tubule cells reabsorb and break down up to 3 grams of albumin per day. In the past, it has been considered that excessive protein loss in the urine is primarily due to problems in the filtering units of the kidneys, rather than due to abnormalities in the reabsorption of protein in the kidney tubules. However, we consider that common abnormalities in the processes within the kidney tubules that regulate both the reabsorption of salt and the excretion of acid may result in concomitant high blood pressure and increased protein loss in the kidney. Thus the overall aim of the project is to investigate the mechanisms by which the complex responsible for protein uptake determines the interrelationship between protein reabsorption and catabolism and the ion transporting proteins in the membrane of the proximal tubule. This project will comprehensively characterise the mechanisms of protein uptake in kidney tubule cells. The exact nature of the interaction of the proteins involved in performing the salt reabsorption and ensuring correct catabolism of protein uptake with the actual protein uptake mechanism will be determined. As persistent proteinuria is the most important predictor of tubulointerstitial pathology and progressive decline in renal function in almost all renal disease, the understanding of the precise mechanism by which this occurs is essential in the design of renoprotective therapies.Read moreRead less
Vitamin D3 Receptor Signalling To Prevent Kidney Failure Due To Polycystic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$468,009.00
Summary
Polycystic kidney disease (PKD) is the most common fatal inherited kidney disease in the world. Kidney failure is the most serious and life-threatening complication of PKD, but currently there is no treatment to prevent this problem. The aim of this project is to determine whether vitamin D3 can prevent kidney failure and hypertension due to PKD. The results of this project could lead to simple and cost-effective treatments to prevent kidney failure in patients suffering from PKD.
Protein Kinases Regulate Salt Reabsorption In The Kidney
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
This proposal is designed to determine how the kidney senses the level of salt in the body and monitors blood pressure. This is critical for diseases such as hypertension, kidney and heart failure, where salt is retained inappropriately. We propose that the kidney uses proteins called kinases that are activated by salt in the kidney. When it is too low, they detect this and cause the kidney to absorb more salt to correct the deficiency. The way that they are able to do this has profound implicat ....This proposal is designed to determine how the kidney senses the level of salt in the body and monitors blood pressure. This is critical for diseases such as hypertension, kidney and heart failure, where salt is retained inappropriately. We propose that the kidney uses proteins called kinases that are activated by salt in the kidney. When it is too low, they detect this and cause the kidney to absorb more salt to correct the deficiency. The way that they are able to do this has profound implications for human heart and kidney disease, and biology in general.Read moreRead less