Research offers hope of new treatments for children with inherited kidney problems
A recent study led by Professors Adrian Woolf and Sue Kimber, funded by Kidney Research UK and other sources, showed that by growing miniature kidneys (‘organoids’) in a laboratory we can learn important new information about kidney problems with genetic causes, and potentially find novel treatments.
Meeting the challenge of inherited kidney problems in children
Children who are born with their kidneys not formed as expected are at particular risk of kidney failure. As technology has advanced, we are increasingly able to identify the genes responsible for these problems.
Adrian and his colleagues’ work has taken this one step further by studying the impact of genetic changes on how kidneys develop. Adrian added: “We want children and their families living with genetic kidney problems to benefit from our growing knowledge. This research shows that by using organoids we can not only improve our understanding of how the kidneys form in people with genetic mutations, but we can also get one step closer to developing new treatments.”
What are organoids?
Organoids are miniature versions of body parts - such as kidneys - that can be grown in laboratories. Organoids allow researchers to look at how kidneys form and work in detail, and they can provide an accurate model of human disease.
In this study, the University of Manchester-based team were able to grow organoids with a genetic change known to lead to kidney failure. This allowed them to look closely at how these alterations affected kidney growth and development.
Preventing kidney problems for future generations
Adrian and colleagues investigated a gene known as HNF1B (hepatocyte nuclear factor 1B), which is involved kidney development in the womb and is one of the most common genetic causes of problems with kidney formation. Using gene-editing technology, they developed organoids with a genetic mutation in HNF1B and found that kidney tubules (which help process urine) did not develop correctly. Importantly, they were also able to identify a potential target for new drug treatments.
Adrian said “By looking at how organoids respond to potential medications ‘in a dish’, this system lets us predict whether different treatments might promote the healthy growth of kidneys in people with genetic changes. More research is needed, but this study gives hope that we will eventually be able to prevent, or at least improve, some genetic causes of kidney failure.”
Emily Surridge, research communications manager at Kidney Research UK added “We are delighted to share this new research from Adrian, Sue and the team in Manchester with the kidney disease community. This work is particularly exciting as it represents real progress towards preventing kidney failure in people born with problems impacting their bladders and kidneys. We would like to thank the team for their work and look forward to seeing the next steps.”
Meet the researcher
Adrian is a researcher at the University of Manchester, and he also set up a multidisciplinary kidney genetic clinic at the Royal Manchester Children’s Hospital. His main interest is working out why people are sometimes born with kidneys and bladders that haven’t grown as expected. These problems are the main reasons that young children require dialysis and kidney transplants. Adrian was also a Trustee at Kidney Research UK from 2012-2018.
Adrian highlighted that his research is a big team effort. He works closely with Professor Sue Kimber, a world-leading stem cell expert, Dr Ioannis Bantounas, a molecular biologist, as well as clinical genetics experts at St Mary’s Hospital and adult kidney doctors in the Manchester Royal Infirmary. Involving families in the long and complex journey to treatment is also critical, and several have already donated blood samples from which stem cells and organoids have been made.