Long Term Sequelae Of Acute Kidney Injury: Identifying The Optimal Model Of Care And Intervention To Enhance Patient Outcome
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Acute kidney injury (AKI) is associated with significant morbidity, mortality and health care costs. It is increasingly recognised as a key driver of progressive kidney disease, and no intervention has been shown to improve the long-term outcome of AKI survivors. This project identifies risk factors for chronic kidney disease, dialysis dependence and death after an episode of AKI, and examines the feasibility, efficacy, and cost-effectiveness of early nephrology review in high risk individuals.
Many people with organ failure such as heart or kidney disease need a transplant to survive. In the case of kidney failure patients can be kept alive by the artificial kidney however this sort of mechanical traeatment is much less satisfactory than a transplant. Unfortunately most patients who would benefit from a transplant are unable to receive one beacuse of the shortage of living or cadaver donors. A possible solution to this shortage of organs for transplantation is to use animal organs. Pi ....Many people with organ failure such as heart or kidney disease need a transplant to survive. In the case of kidney failure patients can be kept alive by the artificial kidney however this sort of mechanical traeatment is much less satisfactory than a transplant. Unfortunately most patients who would benefit from a transplant are unable to receive one beacuse of the shortage of living or cadaver donors. A possible solution to this shortage of organs for transplantation is to use animal organs. Pigs are the most suitable animal donor. However, a pig-to-human organ is rejected immediatly because of the distance between the species. Over the last 10 years, we and others have been trying to understand which genetic differences are important. It is now clear that there are several important differences. One of these is a Blood Group like molecule in the pig that humans react with immediatly on transplantation. This is called the Gal molecule. We and others have been successful in removing the pig gene that makes this molecule. In addition we have added several human genes to pigs to prevent the early vigorous rejection which usually occurs. Organs from these genetically modified pigs have been tested by transplantation into baboons and monkeys. The transplants which used to be rejected within minutes, now survive for months. However, they organs are still rejected by a process which causes clotting in the transplanted organs. We now understand the mechanism andare making genetically modified pigs with human genes which regulate clotting of human blood. This project will test organs from these pigs by transplantation into baboons. We will also make a special strain of pigs in which all these genetic modifications are assembled. This involves the removal of one pig gene and the addition of 4 or 5 human genes. We think it is highly likely that this combination of genetic modifications will make this strain of pigs much more suitable as organ donors.Read moreRead less
New Insights Into The Role Of Renal Endothelial Dysfunction In The Pathogenesis Of Glomerular Injury And Renal Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$577,722.00
Summary
This project will ascertain whether abnormal function of endothelial cells contribute to diabetic and non-diabetic kidney diseases, the leading cause of end-stage kidney disease. The outcome of this study will allow us to reevaluate the role of endothelial cells in kidney scarring, lead us to question our current approaches to the treatment and management of chronic kidney disease and eventually may be helpful for the design of novel therapies to treat chronic kidney diseases.
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.
Contribution Of Bone Marrow-derived Cells To Renal Fibrosis And Elucidation Of Cell Signalling Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$427,703.00
Summary
This study investigates the contribution of bone marrow-derived adult stem cells to the development of renal scarring, an important process proceeding to end-stage renal disease (ESRD). There is increasing evidence demonstrating that bone marrow (BM)-derived cells can transform into renal cells and participate in the repair of damaged renal blood vessels. Our recent study demonstrated BM-derived stem cells can also transform to renal myofibroblasts, the major cell type that contributes to the de ....This study investigates the contribution of bone marrow-derived adult stem cells to the development of renal scarring, an important process proceeding to end-stage renal disease (ESRD). There is increasing evidence demonstrating that bone marrow (BM)-derived cells can transform into renal cells and participate in the repair of damaged renal blood vessels. Our recent study demonstrated BM-derived stem cells can also transform to renal myofibroblasts, the major cell type that contributes to the development of kidney scarring. This suggests that BM-derived adult stem cells have dual roles: to repair or worsen the development of renal scarring. The present study investigates this adult stem cell's transformation and explores the potential measures to enhance the benefits and to block the harmful roles from these adult stem cells. The importance of BM-derived stem cells in the repair of damaged kidney will be determined and thus will provide preliminary insights into the future utilization of BM-derived stem cells in the treatment of chronic renal disease. Understanding the dual roles of BM-derived stem cells in experimental renal scarring, will lead us to question our current thinking and approaches to the treatment and management of renal fibrosis, and perhaps fibrosis in other organs. Evidence of two opposite roles which BM-derived adult stem cells play in the process of renal scarring may be helpful not only for the design of novel therapies to prevent or retard the progression of renal fibrosis, but also for manipulating adult stem cells for the treatment of renal disease.Read moreRead less
The Role Of Renal Dendritic Cells In Infection And Immunity Under Immunosuppression
Funder
National Health and Medical Research Council
Funding Amount
$475,143.00
Summary
Kidney transplantation is the best treatment for kidney failure but it is frequently complicated by bacterial and viral infections that can cause rejection and may cause loss of the kidney. This grant will study the role that dendritic cells in the kidney play in causing rejection and preventing infection. With the knowledge gained from these studies, we will be able to discover new ways to prevent rejection and treat infections of the kidney post transplant.
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
Improving The Quality Of Nephrology Care In Rural Australia (INCRA): Implementation Of Key Guidelines Into Clinical Practice In Rural Or Remote Nephrology Practices.
Palliative Care For Aboriginal And Torres Strait Islander People With End-stage Renal Disease: An Action Research Initiati
Funder
National Health and Medical Research Council
Funding Amount
$295,554.00
Summary
There are significant gaps in current knowledge for providing culturally appropriate and effective palliative care for Aboriginal and Torres Strait Islander people with kidney failure. This project will consider these issues in partnership with the Kowanyama Community and the associated key Aboriginal and Torres Strait Islander and other agencies. Echoing the recommendations by the �National Indigenous Palliative Care Needs Study� this study will address the absence of a culturally appropriate m ....There are significant gaps in current knowledge for providing culturally appropriate and effective palliative care for Aboriginal and Torres Strait Islander people with kidney failure. This project will consider these issues in partnership with the Kowanyama Community and the associated key Aboriginal and Torres Strait Islander and other agencies. Echoing the recommendations by the �National Indigenous Palliative Care Needs Study� this study will address the absence of a culturally appropriate model of care pathway for Aboriginal and Torres Strait Islander people with advanced kidney failure to make effective informed choices for palliative care. Through the use of action research methodology this study will engage with Aboriginal and Torres Strait Islander people to consider these issues, taking into consideration their cultural, spiritual and social needs, those of their family, carers, healthcare personnel and the wider community. Subject to discussions and input from the Aboriginal and Torres Strait Islander people and other key stakeholders it is anticipated that the key areas of interest will focus on spirituality, quality of life, role of the family, carer and community, understandings and experience of kidney failure, treatment options, patient advocacy systems, the need for relocation, and the potential role of advanced care planning. Intervention strategies will also be conducted and evaluated. Subject to discussions and input from the Aboriginal and Torres Strait Islander participants and other key stakeholders it is anticipated that these will focus on a community based education program, development of a culturally appropriate quality of life questionnaire, development and piloting of a culturally appropriate mechanism for people to consider advanced care planning and development and piloting of a patient advocacy process for those from remote areas visiting metropolitan renal - palliative care health services.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