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
Multicentre, Open Label, Randomised, Controlled Trial Of Severe ARF Management With An Augmented Vs Normal CRRT Regimen
Funder
National Health and Medical Research Council
Funding Amount
$1,879,125.00
Summary
Sudden serious kidney failure is a major problem that frequently occurs in patients who are in Intensive Care. For these patients, their chances of survival are significantly decreased. In Australia sudden serious kidney failure is usually treated with continuous kidney support by a kidney machine. A recent study found that by using greater than normal levels of kidney support, that is , running larger volumes of fluid through the kidney machine, patients in Intensive Care Units (ICU's) may be l ....Sudden serious kidney failure is a major problem that frequently occurs in patients who are in Intensive Care. For these patients, their chances of survival are significantly decreased. In Australia sudden serious kidney failure is usually treated with continuous kidney support by a kidney machine. A recent study found that by using greater than normal levels of kidney support, that is , running larger volumes of fluid through the kidney machine, patients in Intensive Care Units (ICU's) may be less likely to die from their sudden serious kidney failure. Despite these positive findings, this high level of kidney support is not commonly used in Australian ICU's. Clearly though, if greater than normal levels of kidney support do increase the chances that individuals will live, then patients should be receiving this treatment. The Australia and New Zealand Intensive Care Society, in conjunction with The George Institute for International Health, propose to conduct a new study involving 1500 patients from ICU's throughout Australia, who require continuous kidney support due to sudden serious kidney failure. These patients will be randomly assigned so that half receive the normally used levels of kidney support and the other half receive kidney support at greater than normal levels. Patients will then be followed for three months to compare the proportions of patients who die in each group. All other outcomes and serious side effects will be closely monitored throughout the study. The results will be available to the public within four years of starting the study, and these are likely to influence the treatment of patients admitted to ICU's with sudden serious kidney failure, not only in Australia but also worldwide.Read moreRead less
I am an intensive care clinician who performs clinical trials and experimental large animal research in multiple aspects of acute and intensive care medicine
The Generation Of High Quality Evidence In Critical Care Medicine Through Multicentre Randomized Controleld Trials And Its Translation Into Practice
Funder
National Health and Medical Research Council
Funding Amount
$240,121.00
Summary
This research program will establish new approaches to sepsis, traumatic brain injury, kidney protection, transfusion, post-operative care, sedation, antibiotics and mobilization of acutely ill patients. Experimental research will help understand why the kidney malfunctions during severe infection. Database investigations will identify of successful patterns of treatment and potential new fields of investigations. Informatics based studies will use electronic data to develop decision support sys ....This research program will establish new approaches to sepsis, traumatic brain injury, kidney protection, transfusion, post-operative care, sedation, antibiotics and mobilization of acutely ill patients. Experimental research will help understand why the kidney malfunctions during severe infection. Database investigations will identify of successful patterns of treatment and potential new fields of investigations. Informatics based studies will use electronic data to develop decision support systems to improve patient care.Read moreRead less
STARRT-AKI: STandard Versus Accelerated Initiation Of Renal Replacement Therapy In Acute Kidney Injury
Funder
National Health and Medical Research Council
Funding Amount
$2,112,447.00
Summary
Acute kidney failure is increasing globally and there are no treatments proven to improve patient outcomes. The STARRT-AKI Study will, as part of an international collaboration, examine the effect upon patient survival of the timing of dialysis initiation in patients with acute kidney failure who are critically ill in intensive care units.
My program of research will focus on one of the most common interventions in medicine _ determining the best resuscitation fluid for resuscitation of critically ill patients. The program includes completion of a major clinical trial in intensive care followed by a series of comparative studies of past and current studies in Australia and internationally. These results will produce clear evidence that will be incorporated in practice guidelines to inform clinicians about optimal practice.