Kidney failure is a major health disorder in Australia and with more diabetes the number of patients waiting for transplant on dialysis is increasing. Current treatments give good initial survival of the kidney transplant but most kidneys are lost due to chronic damage . We propose a number of tolerance strategies in a model of kidney transplantation that will allow transplantation without longterm immunosuppression.
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.
Mechanisms Of Infection Triggered Renal Vasculitis
Funder
National Health and Medical Research Council
Funding Amount
$413,900.00
Summary
Kidney disease, including glomerulonephritis, is an important cause of ill-health in Australia. Some forms of kidney inflammation are linked to infection, but we don�t understand why. This project explores products from bacteria, particularly S.aureus, to work out how bacterial infection affects a form of kidney inflammation - ANCA-associated glomerulonephritis. It will establish how infection related signals activate local and immune cells, and define links between infection and the disease.
Kidney failure is a devastating consequence of diabetes mellitus. Evidence exists that increased amounts of glucose are filtered by the kidney and then together with salt is reaborbed, in patients with diabetes. The increased glucose and salt reabsorption is considered to trigger cellular damage leading to renal failure. The studies will determine if reducing glucose and salt resportion by the kidney protects against the development of renal failure in models of diabetic renal disease.
Randomised Controlled Trial To Determine Efficacy And Safety Of Prescribed Water Intake To Prevent The Progression Of Autosomal Dominant Polycystic Kidney Disease (PREVENT-ADPKD)
Funder
National Health and Medical Research Council
Funding Amount
$746,751.00
Summary
Increasing the daily intake of water is well known to reduce the risk of developing kidney stones but there is growing evidence that it may also benefit other kidney diseases, particularly autosomal dominant polycystic kidney disease (ADPKD). This study will determine if adequate hydration can slow the progression of ADPKD, and could provide a relatively simple and cheap treatment for preventing the onset of kidney failure due to this disease.
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.
Therapeutic Blockade Of Complement Inducing Inflammatory Injury In Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$133,181.00
Summary
ANCA associated vasculitis is an inflammatory disease involving the kidney filters which is a major cause of chronic kidney failure. Current drugs to treat it are toxic. Less toxic treatments are required. In this study we will explore the potential for new treatments targeting complement (a normal blood protein involved in inflammation) to attenuate this disease in mice. We hope to define the role of complement in this disease and the benefits of inhibiting it before we use it in humans.
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.
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.
CKD-FIX: A Randomised, Controlled Trial Of Allopurinol In The Slowing Of Kidney Disease Progression
Funder
National Health and Medical Research Council
Funding Amount
$1,917,147.00
Summary
Chronic kidney disease (CKD) is a major public health problem affecting over 1.5 million Australians and is associated with increased risk of death, heart disease and progression to end-stage kidney disease (ESKD). Current treatments to slow progression to ESKD are limited. The CKD-FIX trial aims to find out whether treatment with allopurinol, a commonly used drug for gout prevention, safely and effectively slows CKD progression. This could lead to significant health and economic benefits.