Serelaxin as a potential treatment for renal dysfunction in cirrhosis
Selective targeting of renal vasoconstriction using serelaxin may modulate renal dysfunction in cirrhosis without affecting systemic blood pressure.
- Hepatorenal syndrome type 1 is a rapidly progressive, but potentially reversible, form of acute kidney injury occurring in patients with liver cirrhosis, characterized by severe renal vasoconstriction and a very poor prognosis. There is a significant unmet need for a widely approved, safe, and effective pharmacological treatment.
- Serelaxin, a recombinant form of the human peptide hormone relaxin-2, has been shown to increase renal perfusion in healthy human volunteers. We tested whether serelaxin could ameliorate renal vasoconstriction and renal dysfunction in cirrhosis.
What did we do and find?
- Administration of serelaxin improved renal blood flow (measured by high resolution ultrasound), oxygenation (measured with BOLD-MRI), and function in two independent animal models of cirrhosis through reversal of endothelial dysfunction and increased activation of nitric oxide signaling in the kidney.
- In an exploratory phase 2 clinical trial in patients with cirrhosis and portal hypertension, serelaxin infusion induced a significant increase in renal blood flow and was safe and well tolerated, with no adverse effects on systemic blood pressure or hepatic perfusion.
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