Treating Hepatorenal Syndrome in the Current Era
Velez, Juan Carlos
ABSTRACT
Hepatorenal syndrome type 1 (HRS-1) is a severe form of acute kidney injury (AKI) that affects individuals with advanced cirrhosis and ascites. The main pillar of its pathogenesis is rooted on marked maladaptive renal vasoconstriction. Because of the lack of a gold standard, establishing the diagnosis requires a meticulous process of recognizing its phenotypical features and ascertaining the absence of strong evidence of an alternative etiology of AKI. This is particularly important because a diagnosis of AKI due to HRS-1 prompts initiation of a specific vasoconstrictor pharmacotherapy. Terlipressin and norepinephrine are the most effective therapeutic agents for HRS-1. Treatment eligibility and choice of agent should follow a systematic assessment of clinical presentation, drug safety profile, practical and logistical considerations around intensive care unit bed availability and proximity of liver transplantation. Independently of the vasoconstrictor used, the goal of therapy is to target a sustained rise in mean arterial pressure to enable renal perfusion. Although albumin has been historically viewed as a key coadjuvant of vasoconstrictor therapy, newer data have emerged demonstrating that albumin may increase the risk for fluid overload. Conversely, diuretics may be safely introduced when clinically applicable. In this review, we navigate through the common challenges faced during the assessment, diagnosis and medical treatment of a patient with decompensated cirrhosis and AKI suspected to be due to HRS-1, emphasizing the newest lessons learned about the role of terlipressin, its safety profile, and the paradigm shift around the role of albumin in the management in HRS-1.
Figure 3. Pharmacological therapy for acute kidney injury (AKI) due to hepatorenal syndrome type 1 (HRS-1). When HRS-1 diagnosis is established, effective vasoconstrictor therapy should be initiated. It is important to be aware that there might be cases in which some degree of acute tubular injury (ATI), abdominal compartment syndrome (ACS) or cardiorenal syndrome type 1 (CRS-1) overlap with HRS-1 and that that should not preclude treating HRS-1 physiology if that is considered to be the main driver for the AKI. Patients at risk for respiratory failure should not be treated with terlipressin [risk factors include ongoing hypoxia, pulmonary infiltrates by imaging, left ventricular systolic or diastolic dysfunction, and acute-on-chronic liver failure (ACLF) grade 3]. Risk:benefit ratio to offer terlipressin when serum creatinine is > 5.0 mg/dL is not favorable. Terlipressin is contraindicated in cases of ongoing ischemia. Once treatment is started with either norepinephrine in the intensive care unit (ICU) or terlipressin in the regular floor, the mean arterial pressure (MAP) should be raised 15 mmHg above baseline. In cases of norepinephrine-induced tachycardia, other vasopressors may be used alone or in combination, such as vasopressin or phenylephrine. In parallel, the patient’s volume status should dictate whether addition of albumin, diuretics or none is needed along the vasoconstrictor therapy. Copyright © 2025 by the American Society of Nephrology AC
