Urinary biomarkers and progression of AKI in patients with cirrhosis

Clin J Am Soc Nephrol. 2014 Nov 7;9(11):1857-67. doi: 10.2215/CJN.09430913. Epub 2014 Sep 2.


Background and objectives: AKI is a common and severe complication in patients with cirrhosis. AKI progression was previously shown to correlate with in-hospital mortality. Therefore, accurately predicting which patients are at highest risk for AKI progression may allow more rapid and targeted treatment. Urinary biomarkers of structural kidney injury associate with AKI progression and mortality in multiple settings of AKI but their prognostic performance in patients with liver cirrhosis is not well known.

Design, setting, participants, & measurements: A multicenter, prospective cohort study was conducted at four tertiary care United States medical centers between 2009 and 2011. The study comprised patients with cirrhosis and AKI defined by the AKI Network criteria evaluating structural (neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], and albuminuria) and functional (fractional excretion of sodium [FENa]) urinary biomarkers as predictors of AKI progression and in-hospital mortality.

Results: Of 188 patients in the study, 44 (23%) experienced AKI progression alone and 39 (21%) suffered both progression and death during their hospitalization. Neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, L-FABP, and albuminuria were significantly higher in patients with AKI progression and death. These biomarkers were independently associated with this outcome after adjusting for key clinical variables including model of end stage liver disease score, IL-18 (relative risk [RR], 4.09; 95% confidence interval [95% CI], 1.56 to 10.70), KIM-1 (RR, 3.13; 95% CI, 1.20 to 8.17), L-FABP (RR, 3.43; 95% CI, 1.54 to 7.64), and albuminuria (RR, 2.07; 95% CI, 1.05-4.10) per log change. No biomarkers were independently associated with progression without mortality. FENa demonstrated no association with worsening of AKI. When added to a robust clinical model, only IL-18 independently improved risk stratification on a net reclassification index.

Conclusions: Multiple structural biomarkers of kidney injury, but not FENa, are independently associated with progression of AKI and mortality in patients with cirrhosis. Injury marker levels were similar between those without progression and those with progression alone.

Keywords: ARF; clinical nephrology; liver failure; outcomes; progression of renal failure.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury / complications*
  • Acute Kidney Injury / mortality
  • Acute Kidney Injury / urine*
  • Acute-Phase Proteins / urine
  • Adult
  • Aged
  • Albuminuria / etiology
  • Albuminuria / urine
  • Biomarkers / urine
  • Disease Progression*
  • Fatty Acid-Binding Proteins / urine
  • Female
  • Hepatitis A Virus Cellular Receptor 1
  • Hospital Mortality
  • Humans
  • Interleukin-18 / urine
  • Lipocalin-2
  • Lipocalins / urine
  • Liver Cirrhosis / complications*
  • Male
  • Membrane Glycoproteins / urine
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Proto-Oncogene Proteins / urine
  • Receptors, Virus
  • Sodium / urine


  • Acute-Phase Proteins
  • Biomarkers
  • FABP1 protein, human
  • Fatty Acid-Binding Proteins
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • Interleukin-18
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins
  • Receptors, Virus
  • Sodium