Characterization of inflammatory response in hepatorenal syndrome: Relationship with kidney outcome and survival

Liver Int. 2019 Jul;39(7):1246-1255. doi: 10.1111/liv.14037. Epub 2019 Feb 17.

Abstract

Background: Several lines of evidence indicate that decompensated cirrhosis is characterized by the presence of systemic inflammation. Hepatorenal syndrome (HRS-AKI) is a unique type of renal failure that occurs at late stages of cirrhosis. However, confirmation of the presence and significance of such inflammatory response in HRS-AKI is lacking.

Aim and methods: To characterize the systemic inflammatory response, as estimated by measuring a large number of cytokines, in 161 patients hospitalized for an acute decompensation of cirrhosis: 44 patients without acute kidney injury (AKI), 63 patients with hypovolaemia-induced AKI and 58 patients with HRS-AKI.

Results: HRS-AKI was characterized by an altered cytokine profile compared to the other two groups, particularly IL-6, IL-8, TNF-α, VCAM-1, fractalkine and MIP-1α. The inflammatory response was not related to presence of bacterial infection, concomitant acute-on-chronic liver failure or severity of renal dysfunction. Patients who responded to terlipressin and albumin had only a decrease in TNF-α and RANTES after treatment without changes in other cytokines. Interestingly, patients with persistent HRS-AKI had higher levels of IP-10 and VCAM-1 compared to those with resolution of HRS-AKI. VCAM-1 was also an independent predictor of 3-month mortality. A systems biology analysis approach showed that the inflammatory status of HRS-AKI was similar to that of chronic nonhepatic inflammatory conditions, such as lupus erythematosus or inflammatory bowel disease.

Conclusion: Hepatorenal syndrome is characterized by a marked systemic inflammatory state, reminiscent of that of nonhepatic inflammatory diseases, that correlates with patient outcomes.

Keywords: AKI; cirrhosis; hepatorenal syndrome; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / mortality*
  • Acute Kidney Injury / therapy
  • Acute-On-Chronic Liver Failure / complications*
  • Acute-On-Chronic Liver Failure / therapy
  • Aged
  • Albumins / therapeutic use
  • Biomarkers / blood
  • Cytokines / blood*
  • Female
  • Hepatorenal Syndrome / etiology
  • Hepatorenal Syndrome / mortality*
  • Hepatorenal Syndrome / therapy
  • Humans
  • Inflammation / pathology
  • Kidney / physiopathology
  • Liver / physiopathology
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / therapy
  • Liver Transplantation
  • Male
  • Middle Aged
  • Prospective Studies
  • Severity of Illness Index
  • Spain
  • Survival Analysis
  • Terlipressin / therapeutic use
  • Vasoconstrictor Agents / therapeutic use

Substances

  • Albumins
  • Biomarkers
  • Cytokines
  • Vasoconstrictor Agents
  • Terlipressin