An international team of scientists has had a breakthrough in a potential treatment for the world’s leading cause of kidney failure in children needing dialysis, it was announced last night.
Led by a team at the University of Bristol, say if the podocyte, a cell in the kidney, can be treated it could block the disease in the early stages.
Most cases of kidney failure in children are due to Haemolytic Uraemic Syndrome (HUS), of which Shiga toxin-associated haemolytic uraemic syndrome (STEC-HUS) is the most common type, the researchers say.
It usually happens after a gut infection, associated with bloody diarrhoea, and the research team have been trying to identify the mechanism underpinning the disease pathway.
Writing in the latest edition of Med, they report using laboratory models and found the podocyte is targeted by the Shiga toxin, which then communicates with local blood vessels. This causes small blood clots to form due to the activation of the ‘complement’ pathway and can lead to an eventual loss of kidney function.
The researchers demonstrated in both mouse models and in human kidney cells that STEC-HUS can be successfully treated by inhibiting the complement pathway early in the disease process with Eculizumab.
Professor Richard Coward, professor of renal medicine at the University of Bristol and consultant paediatric nephrologist at Bristol Royal Hospital for Sick Children, said: “As a children’s kidney doctor one of the most difficult and devastating diseases we treat is STEC-HUS, which causes kidney failure and death in some children. This is normally caused by bacteria that enter the circulation via the gut causing bloody diarrhoea.
“We have now discovered that a cell in the kidney called the podocyte is a key target cell of Shiga toxin and that it can be treated if the ‘complement’ pathway is blocked in the blood early in the disease.”
Early use of Eculizumab can prevent Shiga-toxin driven kidney failure and the drug has therapeutic potential for the disease.
The next stage will see the researchers establishing how quickly Eculizumab needs to be given and carrying out more early trials in children with STEC-HUS.
Bowen at al. Shiga toxin targets the podocyte causing Haemolytic Uraemic Syndrome through endothelial complement activation. Med 19 October 2023. DOI: 10.1016/j.medj.2023.09.002
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