Kidney, Transplant & Diabetes Research Australia is proud to support the clinicians, scientists and students who continue to push the research boundaries in their quest to fight and ultimately eliminate kidney disease and diabetes in Australia and around the world.
Together their focus is on translating science into clinical improvements and better quality of life for patients who suffer with these chronic and often disabling conditions.
The principal areas of research cover a variety of projects which are focused on
- advancing new cell-based treatments such as islet transplantation
- investigating potential therapies to improve cell and organ transplant survival
- providing cutting edge standards of care by developing new ways of evaluating the immune system before transplantation and monitoring immune function after transplantation
- target future therapies by investigating how immune-mediated kidney diseases such as vasculitis and glomerulonephritis develop
- investigating the mechanisms of pre-eclampsia, pregnancy immunology and pregnancy outcomes in women with kidney disease
Advancing new cell-based treatments such as islet transplantation
Islet Cell Transplantation
Type I Diabetes (TD1) is a chronic, life-long autoimmune disease affecting over 140 000 Australians, where the insulin-producing islets of Langerhans in the pancreas are destroyed. The incidence of this disease is increasing and, even with daily insulin therapy, diabetic patients are at greater risk of serious complications including heart attack, stroke, ocular damage and kidney disease.
Researchers supported by Kidney, Transplant & Diabetes Australia are working on the isolation and transplantation of healthy pancreatic islets as an innovative treatment and potential cure for Type I diabetes. As part of the Australian Islet Transplantation Consortium, the laboratory prepares and performs analysis on purified islets that are then transplanted into diabetic patients.
In Australia there are three accredited centres, which form the Australian Islet Consortium. In South Australia, clinicians and scientists at the Royal Adelaide Hospital have performed 10 infusions into 5 patients. Currently 2 of those patients no longer require insulin to control their diabetes and the remaining 3 no longer suffer the life threatening and debilitating hypoglycaemia unawareness they experienced prior to transplantation. Presently islet cell transplantation is funded through the federal and state government Nationally Funded Centres program. A program designed specifically to fund low volume high cost medical procedures.
The team is also focused on improving the overall success of islet transplantation with research into engraftment, immune reaction and rapid cell death post transplant. By better understanding the basic biology of the islet cells researchers hope to combat potential issues with cell death and protect and restore cell function following transplantation.
Islet Cell Auto –Transplantation
A recent grant from Kidney, Transplant & Diabetes Research Australia in conjunction with The Hospital Research Foundation will enable an islet cell isolation centre to be developed at the Royal Adelaide Hospital and assist in the development of human auto islet transplantation.
Currently there is no available program in Australia to provide islet auto- transplantation which could be a potential treatment for people with chronic intractable pancreatitis who suffer severe and usually opioid dependent pain.
Patients would undergo a pancreatectomy (removal of the pancreas) and have reinfusion of their islets following isolation back into their livers. This would prevent diabetes development and surgically cure the intolerable pain. The specific benefit of this form of islet isolation is that it is requires less purification and the patient doesn’t require immunosuppression as the tissue has come from the patient.
- Gene therapy to prevent apoptosis in transplanted pancreatic islets
Researchers have found that the process or programmed elimination of cells in the body, also known as apoptosis is the major cause of islet cell death following an islet cell transplant. Some factors such as insulin-like growth factor II (IGF-II), have the potential to protect the transplanted islets. A current research project is underway to explore the possible option of transferring DNA encoded protective genes to islet cells to improve islet cell functionality and viability after transplants.
- Role of zinc transporters in pancreatic islets:
Researchers are also looking at the damage that occurs during isolation of islet cells due to mechanical and enzymatic stress. This leads to programmed cell death and an insufficient number of cells to meet the body’s metabolic needs following the transplant.
Zinc plays a vital role in DNA replication, enzyme activity and protection against cell death and stress. Zinc is very high in pancreatic beta cells (the cells that secrete insulin) and is important in synthesis, storage and release of insulin. Research undertaken at the Royal Adelaide Hospital has shown that levels of zinc transporter molecules on the surface of islet beta cells vary greatly among diabetic and non-diabetic patients. The next stage of this research study will look at measuring molecule and protein levels of zinc transporters in the islet cells against the protection of insulin production.
- Can endothelial progenitor cells promote successful pancreatic islet transplantation
The islets of the pancreas contain large numbers of blood vessels needed to function properly. Following isolation, islets are rapidly starved of oxygen due to the loss of these blood vessels and this results in loss of function and islet death. Endothelial progenitor cells (EPC) are specialized cells that act as a circulating ‘repair kit’ for blood vessels, assisting with the repair and growth of new vessels and damaged tissue. Transplanting EPC with islets is a potential new therapy to improve islet transplant outcomes.
The investigation of potential therapies to improve cell and organ transplant survival
Cell Therapy for Transplantation
TOLEROGENIC DENDRITIC CELLS FOR TRANSPLANTATION
Dendritic cells (DC) are the sentinels or soldiers of the immune system. They can direct the body’s immune response towards a reactive or tolerant outcome and are vitally important following the transplantation of organs and tissues. Researchers supported by Kidney, Transplant & Diabetes Australia have established a long history working with these important cells and using them to modify the immune system.
Currently the group is involved in modifying the dendritic cells genetically or with sophisticated new methods of drug delivery to stimulate immune tolerance, and administering the dendritic cells to help prevent transplant rejection.
MESENCHYMAL STEM CELLS IN KIDNEY REPAIR AND TRANSPLANTATION
In this project, we are exploring the use of specialised cells called mesenchymal stem cells to prevent kidney injury that occurs during the transplant process. Magnetic resonance imaging (MRI) is used to provide in vivo imaging of iron labelled MSC to determine where they go once delivered and to provide insight into how they exert their beneficial effects.
The development of new ways of evaluating the immune system before transplantation and monitoring immune function after transplantation to provide cutting edge standard of care
The study of immune-mediated kidney diseases such as vasculitis and glomerulonephritis, how disease develops and targets for future therapies
Pregnancy & the Kidney – Obstetric Nephrology and Immunology
PREGNANCY OUTCOMES IN WOMEN WITH RENAL DISEASE
Pregnancy in women with advanced chronic kidney disease, end-stage kidney disease requiring dialysis therapy or after renal transplantation is clinically very challenging. These are high-risk pregnancies with a high rate of complications for both mother and unborn baby even in women who have well-functioning kidney transplants. Researchers are looking at better defining the maternal, obstetric and peri natal factors that affect these pregnancies, in order to improve outcomes for both mother and baby.
Researchers are also investigating the long-term effects on babies of women and men with renal failure or women who are immuno-suppressed during pregnancy.
Kidney disease and the Health of Mothers and Babies
Kidney disease can affect women during pregnancy – often this is the first time kidney disease is diagnosed. Starting a family is an important life issue for young women who have kidney disease, but they may come across serious barriers to parenthood because of their health problems.
Depending on the degree of kidney failure, these pregnancies can be medically very challenging. There are important issues related to blood pressure problems, prematurity and the baby’s growth and health.
Even women with well-functioning kidney transplants have more maternal and fetal health problems than the average Australian pregnancy.
All women with kidney disease require extra counselling and support when planning a family.
This is a special interest area for researchers at Kidney, Transplant & Diabetes Research Australia who are conducting a number of studies to obtain the best possible information about these pregnancies to understand what makes them riskier than most, and how they can intervene to improve outcomes for these mothers and their babies.
The Immune System in Pre-eclampsia:
Pre-eclampsia is the most common medical complication of pregnancy, and can have serious consequences for mother and baby. Often the baby needs to be delivered early to stop the disease. Pre-eclampsia occurs more commonly in women who have diabetes, blood pressure problems or kidney disease.
Our researchers are increasingly learning that pre-eclampsia is a risk factor for health problems later on in life, including high blood pressure, heart disease and kidney disease – the increase in risk is small, but still important enough to recommend a healthy lifestyle and monitoring of health.
We don’t know exactly what causes pre-eclampsia, but the immune system seems to function abnormally.
Our research is exploring many aspects of immune function (regulatory T cells, dendritic cells and NK cells) in normal pregnant women and those with pre-eclampsia to better understand the disease and how we can diagnose and treat it.