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.
Towards Prevention Of Acute Kidney Injury After Cardiac Surgery
Funder
National Health and Medical Research Council
Funding Amount
$771,918.00
Summary
Open heart surgery saves thousands of lives each year in Australia, but often injures the kidney. Kidney oxygen deficiency is a major cause of kidney injury. We propose a new way to manage kidney oxygen levels during heart surgery, by measuring the level of oxygen in the urine in the bladder. We will determine whether low levels of oxygen in the urine during surgery predict later development of acute kidney injury, and whether patient management can be changed to optimize kidney oxygen levels.
Septic shock is a common clinical problem; it is frequently associated with kidney failure that increases mortality. We aim to determine the changes within the kidney that cause it to fail. We will establish whether oxygen levels and blood flow are altered within the kidney, and if blood is shunted through specific blood vessels, reducing flow in critical areas. Importantly, we will determine if clinical treatments used to improve kidney function cause long-term damage by reducing tissue oxygen.
Mechanisms Underlying The Contribution Of Uremic Toxins To Cardiorenal Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$413,533.00
Summary
Cardiorenal syndrome (CRS) is an umbrella term that defines disorders of the heart and kidneys whereby “acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other”. We have demonstrated a significant association between heart and kidney fibrosis (scarring) and levels of a uremic toxin called indoxyl sulphate (IS), in relevant animal models and that blockade of production of this toxin reduces cardiac fibrosis. This project aims to explore this association.
Single Nephron GFR And Tubuloglomerular Feedback Before And After Birth.
Funder
National Health and Medical Research Council
Funding Amount
$402,428.00
Summary
In this project we want to study the forces responsible for the filtration of plasma by the kidney during development. This process is the first step in urine production. It is important to understand kidney function because abnormalities in kidney function can result in high blood pressure and chronic renal disease (requiring dialysis or transplant) in later life. It is reported that up to 40% of the population is salt sensitive i.e. their blood pressure increases when they are on a high salt d ....In this project we want to study the forces responsible for the filtration of plasma by the kidney during development. This process is the first step in urine production. It is important to understand kidney function because abnormalities in kidney function can result in high blood pressure and chronic renal disease (requiring dialysis or transplant) in later life. It is reported that up to 40% of the population is salt sensitive i.e. their blood pressure increases when they are on a high salt diet. The cause of this salt sensitivity is unknown but we believe that it could be due to abnormalities in kidney function during fetal life. Alterations in function occuring during development can have life long effects through a process called fetal programming.Read moreRead less
RENAL VASCULAR HYPERTROPHY AND REMODELLING IN SHR: SYMPATHETIC NERVOUS SYSTEM AND IMPLICATIONS FOR HYPERTENSION
Funder
National Health and Medical Research Council
Funding Amount
$191,561.00
Summary
High blood pressure (hypertension) remains a major health problem for Australians. One in six Australians suffer from hypertension, with consequent increased risk of stroke and heart attack. Anti-hypertensive treatments are available, but must usually be taken for the rest of the patient's life and the cost to the taxpayer of anti-hypertensive drugs is greater than for any other health problem. Prevention of high blood pressure depends on identifying the initial cause - but we still do not know ....High blood pressure (hypertension) remains a major health problem for Australians. One in six Australians suffer from hypertension, with consequent increased risk of stroke and heart attack. Anti-hypertensive treatments are available, but must usually be taken for the rest of the patient's life and the cost to the taxpayer of anti-hypertensive drugs is greater than for any other health problem. Prevention of high blood pressure depends on identifying the initial cause - but we still do not know the cause in over 90% of hypertensive people. This project will study whether overactivity of the nerves to the blood vessels of the kidney might be the cause. There is evidence for this in humans, and in a strain of rats which develops high blood pressure (the spontaneously hypertensive rat). Our experiments will study these rats to see whether nerves affect the structure and function of the blood vessels of the kidney in ways that lead to increased blood pressure.Read moreRead less
Consequences Of Elevated Maternal Glucocorticoids For Early Childhood Renal Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$605,190.00
Summary
A growing body of evidence links maternal stress, such as that precipitated by financial problems or relationship issues (marriage break-up, physical or emotional abuse), with preterm birth and low-birth weight, which in turn has been linked to increased risk of adult disease. Our studies examine how maternal stress impacts on kidney development in childhood and sets the child on the path to cardiovascular disease in adulthood.
Exploring The Physiological, Morphological And Molecular Bases Of Renal Developmental Programming.
Funder
National Health and Medical Research Council
Funding Amount
$422,264.00
Summary
Suboptimal fetal and neonatal development increases our risk of developing a range of diseases in adulthood. The concept that deleterious events during development can influence adult health is termed 'developmental programming'. Obtaining A Healthy Start to Life is a priority research goal of the Australian Government. The kidneys are particularly susceptible to developmental programming. This is in part because the functional units (nephrons) of the kidneys are all formed before birth in human ....Suboptimal fetal and neonatal development increases our risk of developing a range of diseases in adulthood. The concept that deleterious events during development can influence adult health is termed 'developmental programming'. Obtaining A Healthy Start to Life is a priority research goal of the Australian Government. The kidneys are particularly susceptible to developmental programming. This is in part because the functional units (nephrons) of the kidneys are all formed before birth in humans. Thus, if fetal development is suboptimal, babies are at risk of being born with a permanent nephron deficit, with functional and disease consequences. We have shown in male rats that the offspring of a maternal low protein diet have fewer nephrons and lower blood pressure than rats fed a normal diet. These rats display a striking sensitivity in adulthood to the feeding of a high salt diet. We will define the physiological and morphological bases of this sensitivity, and repeat these studies in females, as increasing evidence shows significant sex differences in developmental programming. Defining the molecular mechanisms of developmental programming is the greatest challenge for researchers in the field. We have recently completed the most comprehensive analysis to date of gene expression in the developing mouse kidney, and have shown for the first time that the mouse programmes kidney development. We will use the new techniques of genomics and bioinformatics to study the molecular mechanisms of kidney programming. This mechanistic data will provide an excellent hypothesis engine for future studies on the specific roles of these molecular pathways in developmental programming in all mammalian species.Read moreRead less