An international team of researchers led by the University of Bristol report they have discovered a potential treatment for the world’s leading cause of kidney failure in children needing dialysis.
The findings are published in Med in an article titled, “Shiga toxin targets the podocyte causing hemolytic uremic syndrome through endothelial complement activation.”
“The most common cause of kidney failure in children is due to toxin-producing bacteria that enter the circulation through the gut resulting in a disease called hemolytic uremic syndrome (HUS),” wrote the researchers. “This commonly requires kidney dialysis, with approximately 5% of children developing life-long kidney failure or dying. It has been unclear why this toxin has a predilection for the kidney and what its mechanism of action is. This study shows the kidney podocyte cell is an important target of the toxin and signals to blood vessels through cellular crosstalk, causing complement activation and HUS.”
Using laboratory models, the team found a specific cell in the kidney called the podocyte— which plays a crucial role in renal function—is targeted by the Shiga toxin and then “talks” to local blood vessels causing small blood clots to form. This is due to the activation of the “complement” pathway, and can lead to an eventual loss of kidney function.
The team 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 a drug called Eculizumab.
“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,” explained Richard Coward, PhD, professor of renal medicine at the University of Bristol and consultant pediatric nephrologist at Bristol Royal hospital for Sick Children, and one of the study’s lead authors.
“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.”
Aisling McMahon, PhD, executive director of research and policy at Kidney Research U.K. added: “This research has not only shown exactly how Shiga toxin is able to target the kidney and cause such devastating damage but has also discovered a way in which HUS could be stopped in its tracks using a drug that is already in clinical use. This is another great example of the importance of research in identifying new treatment options for patients, and we look forward to the next steps in this project.”
