Targetting Monocytes With Microparticles To Prevent Kidney Allograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$967,005.00
Summary
Whilst transplantation is lifesaving for many Australians with organ failure, it is a treatment rather than cure as recipients are dependent upon lifelong immunosuppression to prevent transplant rejection. Risks of death due to infection and cancer therefore remain high. We will test a new strategy in mice which modifies recipients of monocytes at the time of transplantation, to enable them to accept and tolerate the organ without ongoing need for expensive and dangerous immunosuppressive drugs.
Investigating New Pathways In Acute Kidney Injury That Are Regulated By CD47
Funder
National Health and Medical Research Council
Funding Amount
$508,848.00
Summary
Acute kidney injury (AKI) is a widespread problem affecting both native and transplanted kidneys. Studies indicate that the incidence has increased more than 200-fold in the last decade, as has mortality. AKI also predisposes to the development of chronic kidney disease. There is no effective therapeutic for treatment or prevention of AKI. This project will investigate new cell signalling pathways regulating AKI with a view to developing these as novel clinical therapies.
Strategies To Achieve Kidney Transplant Tolerance In A Clinically-relevant Model
Funder
National Health and Medical Research Council
Funding Amount
$663,490.00
Summary
The acceptance of kidney transplants without immunosuppression (tolerance) would avoid the side effects of these powerful drugs and improve long-term graft survival. Donor brain death causes inflammation in transplanted kidneys which can block tolerance. In this project, we aim to determine whether expression of a naturally-occurring soluble anti-inflammatory molecule in the liver can prevent this inflammation, allowing tolerance to develop.
Negative Modulators Of Leucocyte Recruitment In The Kidney. The Role Of Slit And Robo.
Funder
National Health and Medical Research Council
Funding Amount
$368,100.00
Summary
Kidney failure is a major health problem in our community, affecting the lives of several thousand individuals and their families. Every year in Australia, about 2,000 new individuals commence dialysis and require ongoing treatment for the rest of their lives. The significant negative impact kidney failure has on quality of life and on life expectancy added to the major shortage of transplant organs, makes the development of effective therapies for kidney diseases an important goal. Our current ....Kidney failure is a major health problem in our community, affecting the lives of several thousand individuals and their families. Every year in Australia, about 2,000 new individuals commence dialysis and require ongoing treatment for the rest of their lives. The significant negative impact kidney failure has on quality of life and on life expectancy added to the major shortage of transplant organs, makes the development of effective therapies for kidney diseases an important goal. Our current therapies have major limitations in terms of their effectiveness and side effects. New therapies which can prevent the progression of kidney disease or prolong the survival of transplanted kidneys may, therefore, have enormous benefits. In order for this to occur, an improved understanding of the common factors underlying kidney disease is required. Our recent studies have been examining the factors influencing kidney inflammation. This process is a significant cause of long term damage in various kidney diseases and in kidney transplants. Our work has identified a potentially major role for recently discovered molecules known as Slit proteins in preventing or decreasing inflammation in the kidney. The level of expression of these molecules in the kidney appears to be rapidly decreased in kidney inflammation and their protective effect is then lost. This imbalance appears to promote the disease process and may be a useful target for the treatment of certain kidney diseases. Our work has found that Slit proteins are able to decrease the movement of white cells (the cells which cause inflammation) out of the blood circulation and into the kidney. The proposed studies aim to better understand the role of these molecules in the kidney as naturally expressed anti-inflammatory agents and to test their potential as therapeutic agents. We hope that the information obtained from these studies will help in the development of new therapies to manage various forms of kidney disease.Read moreRead less
The Effect Of Renal Transplantation And Extended Hours Haemodialysis On Cardiac MRI And Biomarkers.
Funder
National Health and Medical Research Council
Funding Amount
$107,750.00
Summary
Patients with chronic kidney disease (CKD) are at increased risk for cardiovascular disease (CVD). Asymptomatic patients demonstrate changes in cardiac imaging and elevation of cardiac biomarkers which predict outcome. This study will investigate serial cardiac imaging and cardiac biomarkers in patients undergoing live donor renal transplantation and extended hours haemodialysis. Results will enhance our understanding of cardiovascular disease in CKD leading to improved patient outcomes.
Selective Targeting Of Acute Renal Injury By Inhibition Of The Receptor Tyrosine Kinase, C-fms.
Funder
National Health and Medical Research Council
Funding Amount
$443,007.00
Summary
The progression of kidney disease to end-stage renal failure is a major health problem in our community. We have identified that macrophages, a type of white blood cell, plays an important role in causing inflammatory kidney injury. This project will use clinically relevant animal models to test the therapeutic potential of our new approach to selectively remove these cells from the inflamed kidney and thereby protect it from injury.