Reappraising the spectrum of AKI and hepatorenal syndrome in patients with cirrhosis

Nat Rev Nephrol. 2020 Mar;16(3):137-155. doi: 10.1038/s41581-019-0218-4. Epub 2019 Nov 13.


The occurrence of acute kidney injury (AKI) in patients with end-stage liver disease constitutes one of the most challenging clinical scenarios in in-hospital and critical care medicine. Hepatorenal syndrome type 1 (HRS-1), which is a specific type of AKI that occurs in the context of advanced cirrhosis and portal hypertension, is associated with particularly high mortality. The pathogenesis of HRS-1 is largely viewed as a functional derangement that ultimately affects renal vasculature tone. However, new insights suggest that non-haemodynamic tubulo-toxic factors, such as endotoxins and bile acids, might mediate parenchymal renal injury in patients with cirrhosis, suggesting that concurrent mechanisms, including those traditionally associated with HRS-1 and non-traditional factors, might contribute to the development of AKI in patients with cirrhosis. Moreover, histological evidence of morphological abnormalities in the kidneys of patients with cirrhosis and renal dysfunction has prompted the functional nature of HRS-1 to be re-examined. From a clinical perspective, a diagnosis of HRS-1 guides utilization of vasoconstrictive therapy and decisions regarding renal replacement therapy. Patients with cirrhosis are at risk of AKI owing to a wide range of factors. However, the tools currently available to ascertain the diagnosis of HRS-1 and guide therapy are suboptimal. Short of liver transplantation, goal-directed haemodynamically targeted pharmacotherapy remains the cornerstone of treatment for this condition; improved understanding of the underlying pathogenic mechanisms might lead to better clinical outcomes. Here, we examine our current understanding of the pathophysiology of HRS-1 and existing challenges in its diagnosis and treatment.

Publication types

  • Review

MeSH terms

  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / epidemiology*
  • Acute Kidney Injury / therapy
  • Cause of Death*
  • Comorbidity
  • Female
  • Follow-Up Studies
  • Hepatorenal Syndrome / diagnosis
  • Hepatorenal Syndrome / epidemiology*
  • Hepatorenal Syndrome / therapy
  • Humans
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / epidemiology*
  • Male
  • Renal Replacement Therapy / methods
  • Severity of Illness Index
  • Survival Analysis
  • Time Factors