HB-EGF Promotes Recovery From Experimental Acute Renal Failure
Funder
National Health and Medical Research Council
Funding Amount
$337,374.00
Summary
Kidney failure is a frequent complication of serious injury or illness. Although the kidneys generally recover, this can take some time. Before they recover, the inability of the kidneys to function normally adds significantly to the suffering and debility of these sick people. The question we wish to ask is how do the kidneys repair themselves? Ultimately, we would like to know how we could speed up this process. It seems that the kidney remodels after injury by increasing production of growth ....Kidney failure is a frequent complication of serious injury or illness. Although the kidneys generally recover, this can take some time. Before they recover, the inability of the kidneys to function normally adds significantly to the suffering and debility of these sick people. The question we wish to ask is how do the kidneys repair themselves? Ultimately, we would like to know how we could speed up this process. It seems that the kidney remodels after injury by increasing production of growth factors, which are specialised proteins that tell the kidney cells what to do. If we could determine which of these was the most important then it might be possible to give it to patients. If we could even find out how these growth facotrs work, then it might be possible to replace them with a drug that could be more easily administered than a protein.Read moreRead less
The Role Of The Cytoplasmic Domain Of Tissue Factor In Maintenance Of The Glomerular Filtration Barrier.
Funder
National Health and Medical Research Council
Funding Amount
$487,066.00
Summary
This research aims to understand mechanisms of normal kidney function and the development of chronic kidney damage associated with diseases such as nephritis and diabetes. These diseases represent a significant burden of illness in Australia.
To investigate alternative strategies to treat end stage renal disease we have transplanted embryonic kidneys into the wall of the abdominal cavity of adult hosts where they become vascularised and undergo continued but limited development. Strategies to enhance their growth-development and decrease immunogenicity-rejection will now be determined, and the origin of a 'ureter-like' tube of tissue that grows to connect the transplanted embryonic kidney with the recipient bladder investigated.
TGFbeta Isoforms Differentially Regulate Fibrosis And Inflammation In Diabetic Nephropathy Via KLF Transcription Factors
Funder
National Health and Medical Research Council
Funding Amount
$540,639.00
Summary
Progressive scarring and inflammation in the kidney represent the final common injury pathway for diseases that lead to kidney failure, including diabetic nephropathy. This project explores the interplay between the molecular processes that are triggered by high glucose levels in patients with diabetic nephropathy, some of which are deleterious and some potentially 'protective'. By understanding these mechanisms we will be able to prevent and more effectively treat kidney disease in diabetes.
The Role Of Tissue Factor In Renal Ischaemia-Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$268,500.00
Summary
Reestablishment of blood flow to an organ (reperfusion) following temporary cessation or obstruction is essential for survival and recovery of the organ. However while essential for organ survival reperfusion results in damage to the organ in a number of cases, including heart, brain, kidney, and gastrointestinal tract, with important implications for patient morbidity and mortality. In the kidney lack of blood flow can result in acute kidney failure that is a costly condition to manage often re ....Reestablishment of blood flow to an organ (reperfusion) following temporary cessation or obstruction is essential for survival and recovery of the organ. However while essential for organ survival reperfusion results in damage to the organ in a number of cases, including heart, brain, kidney, and gastrointestinal tract, with important implications for patient morbidity and mortality. In the kidney lack of blood flow can result in acute kidney failure that is a costly condition to manage often requiring admission to an intensive care unit and is still associated with a significant risk of death. Reperfusion injury that occurs during renal transplantation is currently thought to be an important contributor to delayed establishment of kidney function following transplantation that in turn may increase the incidence of acute and chronic rejection. The studies outlined in this proposal will investigate how molecules involved in the blood clotting system may contribute to the inflammatory response that occurs upon reperfusion of the kidney following prior obstruction of blood flow. We will study a mouse model of kidney reperfusion injury and using genetically modified mice determine the role of various blood clotting-related proteins in subsequent inflammation and organ damage. The approach to be employed will provide a powerful method to determine the role of various molecules and pathways in contributing to kidney damage after reperfusion injury. Interventions that may reduce the incidence or severity of renal damage following kidney reperfusion injury have the potential to be of major benefit to patients and to reduce health care costs.Read moreRead less
Function Of Factor H-related Protein-5, A Novel Human Plasma Complement Protein Found In Glomerular Immune Deposits
Funder
National Health and Medical Research Council
Funding Amount
$186,430.00
Summary
The Investigators have recently discovered a new protein which is present in human blood and is also seen in the diseased kidneys of patients with nephritis. The new protein is present in all types of nephritis that are caused by antibodies together with another part of the immune system, called the complement system, which is know to have an important role in causing tissue damage in immune diseases. The new protein is a part of the complement system but its exact function is not yet known. The ....The Investigators have recently discovered a new protein which is present in human blood and is also seen in the diseased kidneys of patients with nephritis. The new protein is present in all types of nephritis that are caused by antibodies together with another part of the immune system, called the complement system, which is know to have an important role in causing tissue damage in immune diseases. The new protein is a part of the complement system but its exact function is not yet known. The protein is likely to be important in immune diseases because it is so commonly found in diseased kidneys and other organs with complement-associated disease. In this project we will conduct a series of experiments which will determine how the new protein works in the complement system and also how important the protein is in causing kidney damage in nephritis. Nephritis is the commonest cause of kidney failure in Australia and research directed towards the mechanism of kidney damage has the potential to produce new types of therapy. The complement system also has a major role in other inflammatory diseases and in body defense systems (such as protection against microbial attack). The complement system must be able to distinguish between foreign particles and the body's own tissue and this new protein may have a role in the appropriate regulation of complement to attack the right things in the body. Elucidation of the function of this protein may well assist, therefore, in developing therapies for a variety of inflammatory diseases and infectious diseases, in addition to nephritis.Read moreRead less
Altered Intracellular Signalling In Response To Hyperglycaemia Reflects An Inherent Predisposition To Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$164,061.00
Summary
Diabetic nephropathy affects 30-50% of patients with diabetes mellitus. The reasons as to why only a proportion of patients develop this devastating complication is not clear. Poor control of blood sugar levels has been well characterised as being of aetiological importance in its genesis, but is clearly not the sole factor responsible. Genetic factors appear to predispose individuals to developing diabetic nephropathy, with a significantly higher number of affected patients having a family hist ....Diabetic nephropathy affects 30-50% of patients with diabetes mellitus. The reasons as to why only a proportion of patients develop this devastating complication is not clear. Poor control of blood sugar levels has been well characterised as being of aetiological importance in its genesis, but is clearly not the sole factor responsible. Genetic factors appear to predispose individuals to developing diabetic nephropathy, with a significantly higher number of affected patients having a family history of hypertension and vascular disease. Our own preliminary studies using cells from human kidneys have demonstrated that there are clearly 2 responses observed with respect to alterations in intracellular signalling after exposure to high glucose concentrations and hormones known to be of importance in the development of diabetic nephropathy (such as angiotensin II and insulin-like growth factor-1). These responses appear to be specific to the patient from which the kidney tissue is derived. Thus the aim of the present study is to determine prospectively, whether the groups differ with regards their intracellular signalling and subsequent development of tubulointerstitial pathology in an in vitro model of diabetes mellitus.Read moreRead less