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"The mice with higher levels of suPAR also had dramatic worsening of kidneys compared to mice with normal levels of suPAR when exposed to the same contrast used in patients undergoing coronary angiography," Hayek says. "But when we pre-treated the mice to block suPAR using a monoclonal antibody, we managed to mitigate the development of kidney injury."
The question now, Hayek says, is what's the best way to decrease suPAR levels in humans to lower their risk of kidney failure? His team is looking at treatments and medications already used for other purposes, like statins or immune modulators, in addition to a humanized suPAR antibody which will be explored in clinical trials. Clinical implications for suPAR testing
Hayek says measuring suPAR levels in clinic, which he hopes will be routine in the future, could help providers know when to raise the alarm bells about kidney disease before it starts. In chronic kidney disease, patients don't often experience symptoms early on, and by the time conventional measures such as creatinine confirm a diagnosis, damage has already occurred and is often irreversible.
"This measure could be employed to figure out who's at the highest risk of disease progression or of kidney-related procedural complications, which is currently difficult to determine in clinical practice," Hayek says. "Now that we have extensive data on a role for suPAR in causing kidney disease, we can envision using suPAR-reducing therapies in patients at risk of both chronic and acute kidney disease."
And those with lower kidney injury risk by suPAR levels could more confidently be approved for important cardiac surgery and other procedures.
Hayek says researchers only recently uncovered suPAR's role in kidney disease, and the science is advancing rapidly.
"SuPAR reflect a process that physicians are unable to account for in traditional assessments of kidney disease. We believe this protein acts as the link between inflammation and kidney disease, both chronic and acute," he says.
Along with aging, other medical conditions associated with elevated suPAR levels include smoking, diabetes, autoimmune diseases, sepsis and HIV. And unlike other measures of inflammation, Hayek says suPAR doesn't increase acutely. In fact, levels even remain stable even during heart attacks.
In 2015 his publication, also in the New England Journal of Medicine, reported a 20% loss in kidney function after five years in people with higher suPAR levels. Source:
Michigan Medicine - University of Michigan Journal reference:
Hayek, S.S., et al. (2020) Soluble Urokinase Receptor and Acute Kidney Injury. New England Journal of Medicine . doi.org/10.1056/NEJMoa1911481 .
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