Kidney diseases

Murdoch Children's Kidney Development, Disease and Regeneration laboratory is headed by Professor Melissa Little, and uses stem cells to grow mini kidneys (organoids) using human cells to understand kidney diseases, find treatments, and eventually develop replacement organs.

Overview

The kidney is a complex and essential organ required for maintaining fluid balance, blood volume and electrolyte stability in the body. Chronic kidney disease, if left untreated will lead to kidney failure eventually resulting in death.

Each year, more than 4000 Australians are diagnosed with chronic kidney disease, with a 6% increase in cases per year.  In children with kidney disease, around 50% is inherited, and in many instances the disease-causing mutation is unknown, significantly limiting treatment options.  Current treatments for chronically diseased and failing kidneys include dialysis or transplantation.  Overall, kidney disease costs $1 billion per annum in Australia. There is an urgent need to develop novel therapies for kidney disease, as currently only 1 in 4 renal failure patients will receive a transplant.

At MCRI, our researchers are world leaders in generating models of the kidney from patient stem cells. By recreating human kidney tissue from stem cells, we are now able to ‘model’ the human organ in the laboratory. As these stem cells can be made from patients, it is now possible to precisely investigate the cause of kidney disease in each specific patient.  The hope is to use these mini-kidneys to better understand kidney development and diseases, to test drugs for results and toxicity to find treatments for kidney diseases, and eventually to bioengineer whole replacement kidneys for transplantation.

Projects

The prevalence of chronic kidney disease is continuing to rise worldwide, and with limited treatment options available and a shortage of suitable donor organs, there is a real need for new treatment options. Our laboratory has pioneered methods of using stem cells to grow mini kidneys, also known as kidney organoids in the lab.  Ultimately the utility of these mini-kidney tissues will depend on how effectively they mature and replicate a normal kidney and we are currently working toward improving the structure, size and function of these organoids.  Further understanding the genetic pathways involved in the formation and maturation of each cell type during kidney development will help us better replicate normal development in a dish.  We anticipate this research to be revolutionary to kidney disease treatment options via two avenues:  one is through patient-derived disease modelling and drug screening approaches that further our understanding of kidney diseases and lead us toward new treatment options; the second is through the rebuilding of kidney tissue for transplantation to replace kidney function in the patient.

Modelling kidney disease in a dish using patient-derived stem cells and drug screening

One key area of our kidney research focuses on creating stem cells from patients to model their own kidney tissue in the laboratory.  This allows us to study their disease more closely – an approach called disease modelling.  When we believe there is a genetic cause for the disease, we can also gene edit the stem cells to correct the mutation.  By comparing kidney tissue created from the patient’s mutated and gene corrected cell lines, we can better understand the cause of the disease. This enables us to screen for drugs that may rescue the damage and be useful in the treatment of the patient. This is especially important for rare inherited forms of kidney disease, such as childhood nephrotic syndrome and early onset forms of polycystic kidney disease which are life threatening and have no specific treatments.

Rebuilding the kidney using human pluripotent stem cells

The kidney is a tricky organ when it comes to regenerative treatment options.  A kidney has millions of functional units within it called ‘nephrons’ which develop from kidney stem cells in utero.  Once a child is born, no further nephrons can be created within the kidney, regardless of any damage or disease that may impact on their ability to function properly. We have developed an approach to recreate human kidney tissue, including nephrons, from stem cells using our understanding of how this occurs during development. These mini-kidney tissues can be transplanted into animal models and begin to draw in blood vessels and begin to function. This is the first step in engineering replacement kidney tissue for therapy. There remain many major challenges, including tissue scale, structure and maturation, but we are working on moving from hundreds to thousands of nephrons using bioprinting and bioreactor culture. We are also examining how to improve patterning and connect the transplanted tissue to the host. While this project is a long way from treatment, if successful this may well augment renal function on patients who have not been able to find an appropriate transplant.

Learn more

Meet the researchers and find out more about the research being done in the Kidney Regeneration Lab.

• View the Kidney Regeneration Lab