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.
Diabetic complications are the major cause of the medical burden of both type 1 and type 2 diabetes. It appears that prior episodes of poor sugar control have a sustained impact by continuing to damage blood vessels and the kidney, this phenomenon is known as metabolic memory. In this study an enzyme called Set 7 which modifies the proteins wrapping DNA is considered to play a central role in this phenomenon and could be a potential target for developing new treatments to reduce the burden of di ....Diabetic complications are the major cause of the medical burden of both type 1 and type 2 diabetes. It appears that prior episodes of poor sugar control have a sustained impact by continuing to damage blood vessels and the kidney, this phenomenon is known as metabolic memory. In this study an enzyme called Set 7 which modifies the proteins wrapping DNA is considered to play a central role in this phenomenon and could be a potential target for developing new treatments to reduce the burden of diabetic complications.Read moreRead less
Renal failure is a major cause of morbidity and mortality in persons with diabetes mellitus and accounts for the majority of renal disease worldwide. Renal fibrosis is the end result of progressive kidney disease. The proposed research aims to identify a new strategy by targeting specific channels in kidney cell membranes to arrest the development of enal fibrosis and hence progressive kidney disease caused by diabetes mellitus.
The Beta-blocker To LOwer CArdiovascular Dialysis Events (BLOCADE) Feasibility Study
Funder
National Health and Medical Research Council
Funding Amount
$597,811.00
Summary
The BLOCADE Feasibility Study aims to find out what is needed for a study to see if the drug carvedilol reduces heart disease events in people who need kidney dialysis. Carvedilol is widely used to treat the types of heart disease that are common in people on dialysis but the nature of dialysis may lead to more side effects or to less benefit. A Feasibility Study must be done first to properly plan a large study of carvedilol in people on dialysis that answers this important question.
MPO-ANCA GN is a major cause of renal failure. Current treatments are toxic and poorly effective. Excessive DNA production resulting in prominent deposits of extracellular DNA are seen in glomeruli of patients with MPO-ANCA GN. This study will look at the pathological role of DNA and in a relevant animal model, use DNase I treatment to dissolve deposited DNA and treat anti-MPO autoimmunity and GN. This evidence will allow the introduction of DNase I in clinical trials.
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.
Plasma Exchange And Glucocorticoids In Anti-neutrophil Cytoplasm Antibody Associated Systemic Vasculitis: A Randomised Controlled Trial (PEXIVAS Australia)
Funder
National Health and Medical Research Council
Funding Amount
$420,110.00
Summary
ANCA-associated vasculitis is a life-threatening disease. The PEXIVAS trial will investigate whether plasma exchange, in addition to immunosuppressive therapy and glucocorticoids, will reduce death and the development of severe kidney failure due to this disease. Additionally, the project will also look at whether using a reduced dose of glucocorticoids is just as effective as larger doses in lessening the infectious complications of treatment.
The Therapeutic Role Of Complement Inhibition In ANCA Associated Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$600,964.00
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.
Apoptosis Signal-regulating Kinase 1 (ASK1) Is A Major Pathway Of Stress-induced Renal Injury In Different Types Of Progressive Kidney Disease.
Funder
National Health and Medical Research Council
Funding Amount
$678,865.00
Summary
Oxidative stress plays an important role in progressive kidney disease. We have identified a stress-activated mechanism (the ASK1 pathway) through which oxidative stress may cause kidney disease. We will perform preclinical studies in models of different types of kidney disease with an ASK1 inhibitor drug and genetically modified mice. These studies will provide new insights into the pathogenesis of kidney disease and will determine the potential of ASK1 as therapeutic target in kidney disease.
We have validated CDA1 as an effective target to retard kidney disease in diabetes using a mouse model where we deleted the CDA1gene. We have also developed a novel agent to inhibit CDA1 in order to retard diabetic kidney disease. In this application, we propose to confirm the efficacy of targeting CDA1 using various diabetes models and a range of strategies to target CDA1. We will also rigorously explore translation of these findings to a new treatment for diabetic renal disease.