Recent Advances in the Management of Hepatorenal Syndrome: A US Perspective

Abstract

Acute kidney injury (AKI) is a common complication among decompensated patients with cirrhosis and is associated with significant mortality. 1 Garcia-Tsao G. Parikh C.R. Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008; 48: 2064-2077 Crossref PubMed Scopus (441) Google Scholar In this setting, the most common phenotypes of AKI are hypovolemic/prerenal, acute tubular injury/necrosis, and hepatorenal syndrome (HRS). In this article, the most recent terminology put forth by the International Club of Ascites is used, HRS-AKI, which replaces the prior term HRS type 1. 2 Angeli P. Gines P. Wong F. et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Gut. 2015; 64: 531-537 Crossref PubMed Google Scholar HRS-AKI is a devastating complication of advanced cirrhosis occurring in approximately 17% of AKI cases 1 Garcia-Tsao G. Parikh C.R. Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008; 48: 2064-2077 Crossref PubMed Scopus (441) Google Scholar and is associated with a high 90-day mortality rate of 45% to 51%. 3 Wong F. Pappas S.C. Curry M.P. et al. Terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome. N Engl J Med. 2021; 384: 818-828 Crossref PubMed Scopus (86) Google Scholar ,4 Sanyal A.J. Boyer T.D. Frederick R.T. et al. Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies. Aliment Pharmacol Ther. 2017; 45: 1390-1402 Crossref PubMed Scopus (54) Google Scholar The pathophysiology of HRS-AKI is complex. 5 Biggins S.W. Angeli P. Garcia-Tsao G. et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021; 74: 1014-1048 Crossref PubMed Scopus (110) Google Scholar Because of portal hypertension, blood pools in the splanchnic circulation, leading to decreased effective arterial blood volume. As a result, endogenous vasoconstricting systems are activated, leading to sodium and water retention and decreased kidney perfusion. Overlapping with this process there also is increased gut permeability, bacterial translocation, and up-regulation of systemic inflammatory mediators, a secondary cascade that contributes further to impaired kidney perfusion and concomitantly leads to the functional kidney injury seen in HRS-AKI. These dynamic pathophysiologic changes could be potentiated further by infections, acute-on-chronic liver failure (ACLF), or variceal bleeding.