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Intensivists are being increasingly tasked with caring for critically ill patients with cirrhosis (ie, acute-on-chronic liver failure), many of whom develop acute kidney injury (AKI). Among the most morbid and complex causes of AKI in patients with cirrhosis is hepatorenal syndrome (HRS-AKI). Though HRS-AKI accounts for a fraction of AKI cases in the setting of cirrhosis, recent data suggest that effective pharmacologic treatment of HRS-AKI requires rapid diagnosis to allow for prompt intervention. Consequently, a firm understanding of the diagnosis and treatment of HRS-AKI is vital for all intensivists. In this review, we summarize recent developments in the diagnosis and treatment of HRS-AKI. Chief among these is the recent realization that HRS-AKI is not a diagnosis of exclusion, but instead may coexist with other forms of AKI, such as acute tubular injury, or may develop in the context of pre-existing chronic kidney disease. Moreover, with multiple recent trials suggesting that administration of fixed doses of intravenous albumin to unselected patients with cirrhosis and AKI may cause harm via volume overload and pulmonary edema, no longer is a 48-h trial of intravenous albumin recommended for all patients with AKI and cirrhosis. Instead, the newest guidelines recommend thoughtful assessment of volume status in all patients with AKI and cirrhosis and determination of an HRS-AKI diagnosis within 24 h to allow for prompt initiation of effective therapy. Short of liver transplantation, treatment of HRS-AKI is with vasoconstrictive agents. Though commonly used, midodrine/octreotide should largely be abandoned due to lack of efficacy. While recent trials have confirmed the effectiveness of terlipressin, its use is associated with a risk of potentially fatal respiratory failure and therefore requires careful patient selection and monitoring. As such, treatment of HRS-AKI with norepinephrine in the intensive care unit will remain the primary treatment option for many patients.
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http://dx.doi.org/10.1177/08850666251345408 | DOI Listing |
Clinicoecon Outcomes Res
August 2025
Mallinckrodt Pharmaceuticals, Bridgewater, NJ, USA.
Introduction: Terlipressin is the only Food and Drug Administration-approved medication for adults with hepatorenal syndrome-acute kidney injury (HRS-AKI) with rapid reduction in kidney function. Treatment with terlipressin, particularly in patients with lower serum creatinine (SCr) at diagnosis, improves outcomes. Despite evidence suggesting that treating HRS-AKI at lower SCr thresholds may improve clinical outcomes, the impact on healthcare resource utilization (HCRU) and medical costs of an earlier intervention strategy remains unquantified.
View Article and Find Full Text PDFDig Dis Sci
August 2025
Department of Medicine, University of California-San Francisco, UCSF, 513 Parnassus Avenue, Box 0538, San Francisco, CA, 94143, USA.
Introduction: Limited understanding of kidney dysfunction types and acute kidney injury (AKI) recovery exists due to biopsy risks in decompensated cirrhosis patients. To inform this, we analyzed aptamer-based proteomics and metabolomics to differentiate by AKI diagnosis and recovery.
Methods: A case-control study of 97 patients hospitalized at our institution.
Aliment Pharmacol Ther
July 2025
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Background: Terlipressin is the FDA-approved systemic vasoconstrictor therapy for hepatorenal syndrome-acute kidney injury (HRS-AKI)-a rapidly progressive renal failure occurring in patients with decompensated cirrhosis and ascites. Bradycardia, a known effect of terlipressin, as well as other arrhythmias, has previously been reported in terlipressin-treated patients.
Aim: To assess terlipressin-related cardiac adverse events (AEs) in patients with HRS-AKI.
JHEP Rep
August 2025
Centre of Gastroenterology, Medical Division, Copenhagen University Hospital Hvidovre, Denmark.
Background & Aims: Terlipressin improves renal function in ∼40% of patients with hepatorenal syndrome-acute kidney injury (HRS-AKI). Nonetheless, the pathophysiological mechanisms of terlipressin remain unclear. Therefore, we investigated the cardiovascular changes that occur after terlipressin is given to patients with HRS-AKI.
View Article and Find Full Text PDFAliment Pharmacol Ther
July 2025
State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou
Background: Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a life-threatening complication in decompensated cirrhosis with limited predictive tools for short-term prognosis. Traditional models such as MELD, MELD-Na and Child-Turcotte-Pugh (CTP) have notable limitations in this population.
Aims: This study aimed to evaluate the prognostic performance of the newly developed MELD 3.