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.

 

Reference:

Snowdon VK, Lachlan NJ, Hoy AM, Hadoke PW, Semple SI, Patel D, Mungall W, Kendall TJ, Thomson A, Lennen RJ, Jansen MA, Moran CM, Pellicoro A, Ramachandran P, Shaw I, Aucott RL, Severin T, Saini R, Pak J, Yates D, Dongre N, Duffield JS, Webb DJ, Iredale JP, Hayes PC, Fallowfield JA. Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial. PLoS Med. 2017 Feb 28;14(2):e1002248

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