Our Focus: HRS-AKI

Hepatorenal syndrome with acute kidney injury (HRS-AKI)

HRS-AKI is a serious and rapidly progressive complication of end-stage liver disease that may occur in patients with advanced liver disease and is believed to result from inadequate renal perfusion and intense renal vasoconstriction. While initially reversible, it can lead to irreversible renal failure if inadequately treated.

Prevalence

The definition of kidney disease associated with end stage liver disease has and continues to evolve. New nomenclature (HRS-AKI) and evolving criteria defining the entity continue to be refined. Definitive disease prevalence data lags these changes, leading to calculation based estimates of prevalence. Current literature estimates of prevalence vary with estimates determining that HRS-AKI may impact up to 75,000 individuals in the United States each year.

Treatment

HRS-AKI is a complication of ESLD-induced portal hypertension that leads to splanchnic vasodilation, plasma leakage throughout the abdomen and a significant drop in arterial pressure. This acute drop in arterial pressure triggers a large renal vasoconstriction response resulting in a substantial drop in renal perfusion. Treating HRS-AKI requires improving renal perfusion to avoid acute kidney injury. 

 

Treatment options for HRS-AKI are quite limited, but clinical advances in vasopressin 1a (V1a) receptor agonists are providing promising new options. As a result of their ability to reduce portal hypertension through increasing splanchnic arteriolar vasoconstriction, finely tuned V1a receptor agonists have the potential to redistribute blood volume back to the systemic circulation, reversing the renal vasoconstriction and improving renal perfusion with the additional benefit of enhanced safety profiles compared to the off-label or unapproved use of older drugs currently utilized for this indication.

 

There has been a lack of therapeutic drug innovation for HRS-AKI for several decades.

Sources

 

1. Sepanlou, Sadaf G, et al. “The Global, Regional, and National Burden of Cirrhosis by Cause in 195 Countries and Territories, 1990–2017: A Systematic Analysis for the Global Burden of Disease Study 2017.” The Lancet Gastroenterology & Hepatology, vol. 5, no. 3, 2020, pp. 245–266., https://doi.org/10.1016/s2468-1253(19)30349-8.

2. Ginès, Pere, et al. “Hepatorenal Syndrome.” Nature Reviews Disease Primers, vol. 4, no. 1, 2018, https://doi.org/10.1038/s41572-018-0022-7.

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Ocelot Bio is dedicated to filling the decades-long void for novel medical interventions for HRS-AKI that will finally put better outcomes for patients within reach.

A STRATEGIC VISION MOVING FORWARD