The Role Of Tissue Hypoxia In The Evolution Of Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$509,391.00
Summary
We will determine how low oxygen levels in the kidney lead to kidney disease. We can now measure the levels of oxygen in kidney tissue in rats 24 hours a day, 7 days a week, in a completely non-invasive way. We will study two common kinds of kidney disease. One, acute kidney injury, can result from administration of contrast agents used in x-ray diagnostic procedures. The other, chronic kidney disease, is common in patients with diabetes or high blood pressure.
Acute injury can lead to chronic immune activation in both chronic kidney disease and in transplantation. We will study the role of a class of molecules, the purines, that are released by injury and lead to immune activation. We will focus on the molecular variations and pharmacological blockade of their receptors as potential treatments for kidney disease and transplant graft failure.
TOLERANCE OR REJECTION – THE ROLE OF INNATE IMMUNITY IN DETERMINNG THE FATE OF A KIDNEY ALLOGRAFT
Funder
National Health and Medical Research Council
Funding Amount
$506,413.00
Summary
Transplantation is the optimal management for people with organ failure. Tolerance, to retain transplant function without immunosuppression, remains the key goal but is seldom achieved. We propose to block Toll-like receptor signalling to achieve kidney transplant tolerance in mice. If successful, we would translate this into clinical trials in human, seeking to achieve organ transplantation without the risks of cancer, infection and premature death that are currently faced by organ recipients.
The PRESERVE Trial: Prevention Of Serious Adverse Events Following Angiography
Funder
National Health and Medical Research Council
Funding Amount
$2,424,334.00
Summary
More than 75,000 coronary angiograms are performed each year in Australia. The dye used in angiograms can cause acute kidney injury (AKI); with diabetes, pre-existing kidney disease and heart failure putting people at high risk. Consequences include irreversible kidney failure requiring dialysis and risk of death. Little evidence support currently used prevention strategies. The PRESERVE Trial will recruit 5,200 people to provide definitive evidence to guide prevention of AKI.
Optimising The Therapeutic Efficacy Of Anti-inflammatory Macrophages For Use In Chronic Kidney Diseases
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Chronic kidney disease (CKD) is a major cause of death and morbidity in Australia. Current treatments that are able to delay progression for CKD are limited. As a consequence, more than 2300 additional Australians need kidney replacement each year and many more die of kidney failure. We have reduced and prevented injury in a mouse model of CKD by administering protective white blood cells - macrophages. This project will modify macrophages ex vivo to optimize them for use as a therapy for CKD.
The Role Of Regulatory T Cells In Rapidly Progressive Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$581,113.00
Summary
Inflammation of the kidneys is an important, yet poorly understood cause of kidney disease in Australia. As part of our endogenous defenses against inflammation, we have cells called regulatory T cells that dampen inflammation and are protective. This project will define the role of some of these cells and examine potential ways to use them do dampen kidney inflammation.
Pathogenic Dendritic Cells In Human Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$370,983.00
Summary
The cost of treating end stage kidney disease in Australia is more than a billion dollars per year. Kidney disease is associated with an influx of inflammatory cells. However, current therapeutics fail to target this process due to our poor understanding of inflammatory immune cells in disease progression. This project will investigate the biology of immune cells in human kidney disease. I believe that this study will inform more accurate diagnoses and improved treatments for patients.
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.
Involvement Of The Asciz Gene In Kidney Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$591,128.00
Summary
Congenital abnormalities of the kidney and urinary tract (CAKUT) affect more than 1/500 children. Urogenital development is primarily controlled by a small number of genes that regulate the timing and position of kidney formation. In this application we describe a novel gene involved in this process, establish where it acts, how it regulates gene expression and whether mutations in it cause CAKUT.
Generation Of Renal Cells From Human Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$281,805.00
Summary
This proposal will gather evidence to show that human embryonic stem cells are capable of forming specific cell types of the embryonic human kidney. Once this is established, methods for the maintenance and directed differentiation of these cells to cell types of the mature kidney will be identified and improved. The results obtained will provide a base for future exploration of the possibility that human embryonic stem cell derived cells can be used to treat damaged kidneys.