Growing stem cell-derived kidneys in the laboratory could help better understand a rare genetic kidney disorder and potentially lead to new treatments for children, according to study out of reNEW Melbourne.
Growing stem cell-derived kidneys in the laboratory could help better understand a rare genetic kidney disorder and potentially lead to new treatments for children, according to a Murdoch Children’s Research Institute-led study.
The findings, which were published in the Journal of the American Society of Nephrology, showed that genetically altered mini-kidneys (organoids) created from human stem-cells have identified the possible underlying molecular basis of Steroid-Resistant Nephrotic Syndrome (SRNS).
Nephrotic syndrome is a rare childhood condition, impacting 18-20 children each year at The Royal Children’s Hospital (RCH). Steroid therapy is an effective treatment for 90 per cent of cases but 10 per cent of children have Steroid-Resistant Nephrotic Syndrome, often caused by a genetic mutation, which usually does not respond to treatment with other immunosuppression.
The syndrome causes children to pass too much protein in urine, which leads to severe swelling. When the symptoms don’t respond to immunosuppression, the only options left are to replace the protein through intravenous (IV) infusions and reduce blood supply to the kidney with medication.
Unfortunately, the disorder can progress to end-stage kidney disease, with most children eventually needing a kidney transplant.
The study, led by Professor Melissa Little and Dr Aude Dorison, aimed to investigate the genetic basis of SRNS, in which mutations occur in a gene called NPHS2 and affect the protein PODOCIN which is essential for kidney filtration.
To do this, they used gene editing techniques to replicate the variations in the NPHS2 gene that are present in the syndrome and compared mini-kidneys created from healthy gene-edited human stem cells to better understand the disease.
“We found that these gene variations had several effects. They reduced levels of PODOCIN, changed its location in the cell and altered its interactions with other proteins,” Professor Little said. “Additionally, we found that all the variants caused cell death, which could provide some insight into how this condition occurs.”
By using human stem cell-derived kidney organoids, the researchers gain a more realistic understanding of how these genetic variants contribute to Steroid-Resistant Nephrotic Syndrome and could help improve our understanding of the disorder.
Professor Little said she hoped the research would lead to an improved understanding of this rare disorder and potentially enable the development of better treatments for children in the future.