Randomised Controlled Trial To Determine Efficacy And Safety Of Prescribed Water Intake To Prevent The Progression Of Autosomal Dominant Polycystic Kidney Disease (PREVENT-ADPKD)
Funder
National Health and Medical Research Council
Funding Amount
$746,751.00
Summary
Increasing the daily intake of water is well known to reduce the risk of developing kidney stones but there is growing evidence that it may also benefit other kidney diseases, particularly autosomal dominant polycystic kidney disease (ADPKD). This study will determine if adequate hydration can slow the progression of ADPKD, and could provide a relatively simple and cheap treatment for preventing the onset of kidney failure due to this disease.
A New Signaling Interface Shapes Cystic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$586,846.00
Summary
This grant investigates the previously uncharacterised association between the INPP5E and AURKA proteins. Both are involved in cell signaling and the development of cystic kidney disease. We will study the nature of this interaction and investigate whether it is possible to ameliorate kidney disease by inhibiting their actions in the developing and adult kidney.
Characterising The Molecular Basis Of Cystic Kidney Diseases Using Kidney Organoids Created By Directed Differentiation Of Patient-derived, Induced Pluripotent Stem Cells.
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
Inherited genetic mutations cause almost half of chronic kidney diseases in children. In most cases we do not know what the mutation is or how it causes kidney disease. In this study we will turn skin cells from children with kidney disease into stem cells and then use these to make a mini-kidney in a dish. This will act as a model of kidney disease allowing us to understand what the problem is at the level of changes within the cells. This may result in new ways of treating kidney disease.
Cyclin Dependent Kinases As Drug-Targets To Reduce Renal Cyst Formation And Scarring In Polycystic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$319,446.00
Summary
Polcystic kidney disease (PKD) is one of the most common genetic diseases in humans. The most common type (autosomal dominant-PKD) affects approximately 1:400 to 1:1000 individuals worldwide. Kidney failure is the most debilitating and serious complication of PKD, and it accounts for approximately 10% of the cases of end-stage kidney requiring artificial kidney treatment (dialysis) or transplantation. Over the last decade, major advances have been made in preventing kidney failure due to diabeti ....Polcystic kidney disease (PKD) is one of the most common genetic diseases in humans. The most common type (autosomal dominant-PKD) affects approximately 1:400 to 1:1000 individuals worldwide. Kidney failure is the most debilitating and serious complication of PKD, and it accounts for approximately 10% of the cases of end-stage kidney requiring artificial kidney treatment (dialysis) or transplantation. Over the last decade, major advances have been made in preventing kidney failure due to diabetic kidney disease, but these are ineffective for PKD. As such, currently, there is no treatment to prevent kidney failure due to PKD, and new therapies are needed. PKD is characterised by the development of multiple cysts in the kidney, which enlarge and destroy normal kidney tissue. The growth of the cysts is due to uncontrolled growth (cell division) of the cells of the kidney (epithelial cells), which causes cyst formation. In recent years, gene mutations in proteins called polcysytins are thought to be responsible for the cause of the disease. However, the genetic mutations in PKD are complex (>30 types for autosomal dominant PKD alone), and it is unlikely that gene therapy will be possible with current technology in the near future. A simpler approach is to develop 'drugs' that target the consequences of the mutation. This project will investigate the role of a group proteins, called cyclin-dependent kinases (CDKs) in PKD. CDKs which are enzymes that are critical in promoting cell division. Our preliminary data shows that CDKs are upregulated in PKD. The aim of this project is to establish the importance of CDKs in PKD, and examine the effect of new drugs (CDK inhibitors) in maintaining in preventing cyst growth and kidney scarring in PKD. CDK inhibitors are currently being tested in phase 1 and 2 clinical trials in patients with cancer, and this will facilitate the translation of the findings of this project to humans with PKD.Read moreRead less
Neural Versus Humoral Activation Of The Sympathetic Nervous System In Renal Disease
Funder
National Health and Medical Research Council
Funding Amount
$293,567.00
Summary
In the healthy body, the kidney and the sympathetic nervous system work together to keep our blood pressure in the normal range, both in the short and long term. When people have kidney disease, this system fails and people can develop high blood pressure. High blood pressure can lead to heart attack and stroke, and so is a serious complication for people who already have kidney disease. It has previously been believed that major factors in this process are fluid retention and a circulating horm ....In the healthy body, the kidney and the sympathetic nervous system work together to keep our blood pressure in the normal range, both in the short and long term. When people have kidney disease, this system fails and people can develop high blood pressure. High blood pressure can lead to heart attack and stroke, and so is a serious complication for people who already have kidney disease. It has previously been believed that major factors in this process are fluid retention and a circulating hormone called angiotensin II, but we believe that the sympathetic nervous system is also very important. Further, we believe that sensory nerves in the kidney tell the brain something is wrong in the kidney, making the sympathetic nervous system increase blood pressure inappropriately. We will examine the relative role of the sensory nerves and the hormone angiotensin II in driving the sympathetic nervous system to increase blood pressure, using three different rat models of kidney disease. One of these models is a new rat model of polycystic kidney disease, which is the fourth most important cause of renal disease in Australia. We want to determine what parts of the brain are important in the pathway, and will also test treatments that block the two different pathways (nerves vs. hormones) to see what is the most effective way of controlling not only blood pressure but also slowing down the progression of kidney and heart disease. This work is important as it will not only help us understand how the brain and kidney communicate with each other, but will also have the potential to improve quality of treatment for people with kidney diseaseRead moreRead less
Interactions Between Systems That Control Sodium Channels In Renal Epithelia
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
The transport of sodium ions by the kidney, gut and lungs not only regulates blood pressure, it also regulates the amount of fluid in the gut and in the lungs. One of the most important proteins that underlie the transport of sodium in these tissues is the so-called epithelial sodium channel. The activity of these epithelial sodium channels is regulated by a wide variety of systems. Some of these regulatory systems act in response to changes in the body's requirements for sodium transport. Other ....The transport of sodium ions by the kidney, gut and lungs not only regulates blood pressure, it also regulates the amount of fluid in the gut and in the lungs. One of the most important proteins that underlie the transport of sodium in these tissues is the so-called epithelial sodium channel. The activity of these epithelial sodium channels is regulated by a wide variety of systems. Some of these regulatory systems act in response to changes in the body's requirements for sodium transport. Others act in response to changes in capacity of cells in which the sodium channels are found to continue transporting sodium. In this project we will study the mechanisms that regulate the activity of the epithelial sodium channels, and in particular, how these mechanisms interact so as to maintain a level of sodium channel activity that is appropriate to both the needs of the organism and to the needs of the sodium transporting cells. The outcomes of this project will be improved understanding of the function of the kidney, gut and lungs in both health and disease. It may also lead to novel drug targets for treatment of major diseases in which the activity of sodium channels is abnormal. These disease include hypertension, cystic fibrosis, pulmonary oedema and influenza.Read moreRead less
Regulation Of The Epithelial Sodium Channel By Cytosolic Chloride And Pro-inflammatory Cytokines
Funder
National Health and Medical Research Council
Funding Amount
$219,750.00
Summary
The regulation of sodium transport by the epithelial sodium channel is essential for the maintenance of blood pressure and the correct amount of fluid in the respiratory tract and gut. Hyperactivity of the sodium channels leads to increased blood pressure and clogging of the gut and bronchi due to dehydration of the surface fluid. Reductions in the activity of the sodium channels lead to abnormally low blood pressure and the accumulation of fluid in the lungs such as occurs in influenza, high al ....The regulation of sodium transport by the epithelial sodium channel is essential for the maintenance of blood pressure and the correct amount of fluid in the respiratory tract and gut. Hyperactivity of the sodium channels leads to increased blood pressure and clogging of the gut and bronchi due to dehydration of the surface fluid. Reductions in the activity of the sodium channels lead to abnormally low blood pressure and the accumulation of fluid in the lungs such as occurs in influenza, high altitude pulmonary oedema and in cardiogenic pulmonary oedema. The present project will examine the mechanisms by which sodium channels are regulated. It will focus on the mechanisms by which cytosolic chloride and inflammatory mediators regulate the activity of the channels.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.