The Role Of Peroxisome Proliferator Activated Receptor Gamma In Sodium Transport In Human Proximal Tubule Cells
Funder
National Health and Medical Research Council
Funding Amount
$566,946.00
Summary
Renal failure accounts for a considerable component of the excess morbidity and mortality observed in patients with diabetes mellitus. In addition, the emotional, social and cost to the community of dialysis is enormous. PPARgamma is activated by drugs that have been recently introduced for the treatment of type 2 diabetes mellitus. The propensity for these drugs to cause fluid retention has emerged recently as the most common serious adverse drug reaction associated with these compounds. the de ....Renal failure accounts for a considerable component of the excess morbidity and mortality observed in patients with diabetes mellitus. In addition, the emotional, social and cost to the community of dialysis is enormous. PPARgamma is activated by drugs that have been recently introduced for the treatment of type 2 diabetes mellitus. The propensity for these drugs to cause fluid retention has emerged recently as the most common serious adverse drug reaction associated with these compounds. the definitive cause of fluid retention with the use of PPAR gamma agonists is not known. Studies reported in the last 12 - 18 months have suggested that a common pathway may be involved in the development of the fluid retention, the high blood pressure and the scarring that occurs in the kidney. This project will be the first to provide a comprehensive examination of the effect of PPARgamma induction on renal sodium absorption and fluid retention in the human proximal tubule cells and the potential molecular mechanisms underlying them. This will provide insight as to potential adjuvant treatments for patients with diabetes.Read moreRead less
Understanding And Optimising The Delivery Of Chronic Disease Care For Better Cardiovascular Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$483,402.00
Summary
The proposed research program will undertake research that utilises existing clinical information and structures. This information will provide evidence in a cost effective manner. A particular project will examine current treatment delivered to people with chronic disease. A second project will embed a study of the optimum level of sodium exposure in dialysis within routine clinical practice. The outcome will be a cost-efficient study that will potentially lead to improve outcomes.
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.
AMP-activated Protein Kinase (AMPK) In Acute Renal Failure
Funder
National Health and Medical Research Council
Funding Amount
$401,523.00
Summary
Acute renal failure is a common complication of any severe illness. Generally, it is the lack of blood flow, or food that leads to this problem. People who are ill are unable to provide adequate blood flow to their kidneys, so the kidneys become diseased and fail to function. This can be fatal. There are, however, mechanisms in the kidney that are designed to avoid this shortage of energy. The aim of these studies is to find out what these protective mechanisms usually do in the kidney, and unde ....Acute renal failure is a common complication of any severe illness. Generally, it is the lack of blood flow, or food that leads to this problem. People who are ill are unable to provide adequate blood flow to their kidneys, so the kidneys become diseased and fail to function. This can be fatal. There are, however, mechanisms in the kidney that are designed to avoid this shortage of energy. The aim of these studies is to find out what these protective mechanisms usually do in the kidney, and understand why they are not more active. We hope to find ways to switch them on earleir, using drugs, so as to protect the kidneys from injury.Read moreRead less
Two-photon Microscopy Of Albumin Handling By The Intact Kidney
Funder
National Health and Medical Research Council
Funding Amount
$346,602.00
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 use cutting-edge microscopic imaging technology to investigate the mechanisms of protein uptake in the intact kidney. This information will be integrated with data obtained from our molecular physiology experiments to define how the kidney handles protein. 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