Understanding How Sepsis Causes Kidney Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$471,770.00
Summary
Acute renal failure is a serious condition that affects up to 20% of patients in Intensive Care Units. Sepsis and septic shock remain the most important causes of acute renal failure in critically ill patients. Despite our ability to support vital organs and resuscitate patients, the incidence and mortality of septic acute renal failure remain unacceptably high at up to 55%. There have been no major advances in our understanding of its pathogenesis and in its prevention or treatment over the las ....Acute renal failure is a serious condition that affects up to 20% of patients in Intensive Care Units. Sepsis and septic shock remain the most important causes of acute renal failure in critically ill patients. Despite our ability to support vital organs and resuscitate patients, the incidence and mortality of septic acute renal failure remain unacceptably high at up to 55%. There have been no major advances in our understanding of its pathogenesis and in its prevention or treatment over the last 50 years. The traditional view is that sepsis-induced renal failure results from reduced perfusion of the kidney secondary to the low blood pressure. In a model of sepsis in sheep with renal failure, we demonstrated, however, that renal blood vessels dilated and blood flow increased. Furthermore, renal function improved following treatment with vasoconstrictor drugs that raised blood pressure and renal blood flow. These findings indicate that renal ischaemia is not the cause of the renal dysfunction in sepsis. We hypothesise that sepsis causes renal vasodilatation, which reduces glomerular filtration rate and renal function, and induces a delayed development of apopotosis. We will study in sepsis 1) the effects of a treatment to increase glomerular filtration rate 2) the development of apoptosis and the effect of an anti-apoptotic drug, and 3) whether there is bioenergetic failure in the kidney in sepsis and the effects of treatments on this. Finally, in septic patients we will measure renal blood flow and determine the effects of our novel treatment on this and renal function. These studies will significantly increase our understanding of the factors causing acute renal failure in sepsis. They are likely to lead to the development of new therapies to improve renal function in sepsis and their effectiveness will be examined in septic animals and patients.Read moreRead less
Genomic Analysis Of Host Response To Influenza A Infection
Funder
National Health and Medical Research Council
Funding Amount
$168,530.00
Summary
Influenza virus infects millions of people globally. However, it remains poorly understood why some infected individuals succumb to life threatening complications whilst others recovered relatively unaffected. This study use advance molecular technique to study influenza infection. It aims to identify the key steps in our immune systems that are progressively disrupted during influenza infection and how this process lead to a break down in our natural defence against the virus.
Improving Long-term Mortality Rates Following Sepsis.
Funder
National Health and Medical Research Council
Funding Amount
$99,682.00
Summary
It is estimated that 37.9 million patients survive sepsis each year. Studies have demonstrated that among patients who survive for 30 days after admission for sepsis, over 40% die in the following two years. There are currently no guidelines that provide recommendations on post-hospital management of sepsis. This research programme aims to identify those patients at greatest risk of death and implement post-sepsis care with the aim to significantly reduce long-term mortality after sepsis.
This program directly addresses the major threat of antimicrobial resistance , bringing together the power of modern genomics and the promise of novel positive therapies to eradicate AMR organisms and AMR genes from individuals at risk from severe infection.
DIAMONDS - Diagnosis And Management Of Febrile Illness Using RNA Personalised Molecular Signature Diagnosis
Funder
National Health and Medical Research Council
Funding Amount
$391,897.00
Summary
We will develop and validate technologies to provide rapid diagnosis to patients presenting to primary care and hospitals on the basis of gene expression signatures in blood.
Critical Infection: Ecological Solutions To Antibiotic Resistance
Funder
National Health and Medical Research Council
Funding Amount
$561,362.00
Summary
The applicant will apply new types of microbial data and diagnostic tools to early interventions in the critically ill and directly test their impact on clinical outcomes. He will also introduce novel therapies to restore antibiotic susceptibility to enteric bacteria and examine the clinical and microbiological effects of antibiotic decontamination of the critically ill in newly funded project grants. Overlapping research themes all link directly to his clinical and professional roles.