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The Effects Of Maternal Health On Fetal Kidney Development And Its Function
Funder
National Health and Medical Research Council
Funding Amount
$297,338.00
Summary
There is an epidemic of renal disease among Australian aborigines. While much of this could have been prevented by effective control of Group A streptococcal skin infections, there is also evidence that the high susceptibility to end-stage renal disease is related to poor intrauterine development of the kidney as low- birth weight is a predisposing factor. Mothers, whose renal function is impaired, tend to have babies which are low birth weight. There is no knowledge about the effects of materna ....There is an epidemic of renal disease among Australian aborigines. While much of this could have been prevented by effective control of Group A streptococcal skin infections, there is also evidence that the high susceptibility to end-stage renal disease is related to poor intrauterine development of the kidney as low- birth weight is a predisposing factor. Mothers, whose renal function is impaired, tend to have babies which are low birth weight. There is no knowledge about the effects of maternal renal dysfunction on development of the fetal kidney. We have recently developed an animal model in which we can study the effects of maternal renal dysfunction on the development of the kidney of her offspring. Human beings form 60% of the functional units (nephrons) in the kidney in the last trimester. Sheep, like human beings (and unlike rats), completely form all the nephrons that they will ever have, during intrauterine life. While the fetal kidneys play an essential role in the formation of amniotic fluid, regulation of fetal fluid and electrolyte homeostasis depends on maternal renal function via transplacental transfer. If maternal renal function is reduced, it is likely that the fetal kidneys will be exposed to a greater volume and solute load through transplacental equilibration. This may have a profund effect on renal development especially if coupled with an inadequate maternal diet and a high maternal salt intake. Under these conditions we predict that development of the fetal kidney will be impaired and renal capacity after birth, reduced. This means that the kidney will 'age' more rapidly. Thus the affected individual would be predisposed to renal disease in adult life. In our animal model we will study the effects and interactions of maternal renal insufficiency, poor fetal nutrition and a high maternal salt intake on fetal kidney development and function.Read moreRead less
Hypertension Induced By Prenatal Glucocorticoid Exposure: Roles Of Cerebral And Renal Renin-angiotensin Systems
Funder
National Health and Medical Research Council
Funding Amount
$497,500.00
Summary
High blood pressure is a major public health problem in Australia and other developed countries as it is a common risk factor for stroke, heart failure and kidney damage. At present, there is a great interest in the possibility that high blood pressure in adults can result from stresses experienced by the fetus before birth. However, it is not known how prenatal compromise could lead to high blood pressure. We have recently established an animal model (using sheep) in which brief exposure to glu ....High blood pressure is a major public health problem in Australia and other developed countries as it is a common risk factor for stroke, heart failure and kidney damage. At present, there is a great interest in the possibility that high blood pressure in adults can result from stresses experienced by the fetus before birth. However, it is not known how prenatal compromise could lead to high blood pressure. We have recently established an animal model (using sheep) in which brief exposure to glucocorticoids - known as stress hormones - administered to the mother during early gestation results in high blood pressure in the offspring in adulthood. Increased levels of these hormones could occur in women at times when many may be unaware of their pregnancy (ie. smoking marijuana, chronic insomnia, accidents, loss of loved one, physical or mental stress or abuse). In addition, high doses of synthetic glucocorticoids might be given to pregnant patients for the treatment of asthma and acute migraine. The early origins of hypertension are of considerable importance to a large section of the community, namely the 25% who develop hypertension at the age 45 or over. If even a small proportion of hypertension can be prevented by reducing fetal exposure to excess glucocorticoids the impact on cardiovascular illness may be large. This research proposal has the potential to explain the basis for at least some of the 'essential' hypertension for which a mechanism has not been discovered after decades of research. This project will examine the separate roles of the kidney and brain, and in particular will determine whether permanent changes can be induced by exposure to stress hormones during early fetal life. Knowledge gained from this project could be used in devising strategies aimed at preventing or treating high blood pressure in adults.Read moreRead less
Fetal Cardiovascular Development And The Impact Of Chronic Hypoxia And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$307,232.00
Summary
Low birth weight occurs in 7% of Australian babies and is associated with an increased risk of cardiovascular disease in adult life. Understanding the mechanisms underlying heart and blood vessel development in low birth weight babies will lead to improved identification and intervention in those individuals at risk of cardiovascular disease in adult life, improving heart health for Australians. Reducing cardiovascular disease will improve both quality and quantity of life for Australians.
Heart-lung Interactions Determine Right Ventricular Function In The Perinatal Period.
Funder
National Health and Medical Research Council
Funding Amount
$421,980.00
Summary
Birth, and the ensuing stress of newborn life, requires the heart to dramatically increase its level of functioning. Understanding how this process occurs remains a key problem as the heart lacks any ability to increase its level of functioning immediately before birth. Failure to effect this increase in heart function promptly at birth has serious implications for the well being of the newborn and represents a major problem in newborn medicine. Of the 250,000 babies born each year in Australia, ....Birth, and the ensuing stress of newborn life, requires the heart to dramatically increase its level of functioning. Understanding how this process occurs remains a key problem as the heart lacks any ability to increase its level of functioning immediately before birth. Failure to effect this increase in heart function promptly at birth has serious implications for the well being of the newborn and represents a major problem in newborn medicine. Of the 250,000 babies born each year in Australia, as many as 5,000 require intensive care primarily for cardiorespiratory complications. Accurate diagnosis and effective treatment of these infants demands knowledge of the normal heart adaptations that accompany birth, adaptations that are critically linked to the way in which the heart and the lungs interact. This project investigates how interactions between the heart and the lungs determines heart function throughout life. By understanding this process we will provide essential information that will aid the diagnosis and treatment of sick neonates undergoing intensive care.Read moreRead less
Diagnostic Tests To Predict Risk For Life Threatening Pregnancy Complications
Funder
National Health and Medical Research Council
Funding Amount
$682,824.00
Summary
The main complications of pregnancy, preeclampsia, preterm birth and intrauterine growth restriction afflict 19% of first pregnancies and are life threatening to the mother or baby in 6% of pregnancies. Currently we have no way of knowing which women will suffer these diseases until symptoms manifest. We aim to develop genetic tests that can predict which women are at risk. This will permit earlier interventions that will improve the health of pregnant women and their babies.