Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2017 Jul;15(7):1003-1013.e3.
doi: 10.1016/j.cgh.2016.11.035. Epub 2016 Dec 21.

Urine Interleukin 18 and Lipocalin 2 Are Biomarkers of Acute Tubular Necrosis in Patients With Cirrhosis: A Systematic Review and Meta-analysis

Jeremy Puthumana  1 , Xavier Ariza  2 , Justin M Belcher  3 , Isabel Graupera  2 , Pere Ginès  2 , Chirag R Parikh  4
Affiliations
Meta-Analysis

Urine Interleukin 18 and Lipocalin 2 Are Biomarkers of Acute Tubular Necrosis in Patients With Cirrhosis: A Systematic Review and Meta-analysis

Jeremy Puthumana et al. Clin Gastroenterol Hepatol. 2017 Jul.

Abstract

Background & aims: Acute kidney injury (AKI) is a common complication in patients with cirrhosis that increases mortality. The most common causes of AKI in these patients are prerenal azotemia, acute tubular necrosis (ATN), and hepatorenal syndrome; it is important to determine the etiology of AKI to select the proper treatment and predict patient outcome. Urine biomarkers could be used to differentiate between patients with ATN and functional causes of AKI. We performed a systematic review and meta-analysis of published studies to determine whether urine levels of interleukin (IL)18 and lipocalin 2 or neutrophil gelatinase-associated lipocalin (NGAL) are associated with the development of ATN in patients with cirrhosis.

Methods: We searched MEDLINE, Scopus, ISI Web of Knowledge, and conference abstracts through December 31, 2015, for studies that assessed urine biomarkers for detection of acute kidney injury in patients with cirrhosis or reported an association between urine biomarkers and all-cause mortality in these patients. We included only biomarkers assessed in 3 or more independent studies, searching for terms that included urine biomarkers, cirrhosis, NGAL, and IL18. We calculated the pooled sensitivities and specificities for detection and calculated the area under the receiver operating characteristic curve (AUC) values using a bivariate logistic mixed-effects model. We used the χ2 test to assess heterogeneity among studies.

Results: We analyzed data from 8 prospective studies, comprising 1129 patients with cirrhosis. We found urine levels of the markers discriminated between patients with ATN and other types of kidney impairments, with AUC values of 0.88 for IL18 (95% confidence interval [CI], 0.79-0.97) and 0.89 for NGAL (95% CI, 0.84-0.94). Urine levels of IL18 identified patients who would die in the hospital or within 90 days (short-term mortality) with an AUC value of 0.76 (95% CI, 0.68-0.85); NGAL identified these patients with the same AUC (0.76; 95% CI, 0.71-0.82).

Conclusions: In a systematic review and meta-analysis, we found that urine levels of IL18 and NGAL from patients with cirrhosis discriminate between those with ATN and other types of kidney impairments, with AUC values of 0.88 and 0.89, respectively. Urine levels of IL18 and NGAL identified patients with short-term mortality with an AUC value of 0.76. These biomarkers might be used to determine prognosis and select treatments for patients with cirrhosis.

Keywords: Cytokine; Prediction; Prognostic Factor; Survival.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: Pere Ginès declares that he has received research funding from Ferring Pharmaceuticals, Grifols S.A., and Sequana Medical. He has participated on Advisory Boards for Noorik, Ikaria, Ferring Pharmaceuticals, Promethera, and Sequana Medical. The remaining authors disclose no conflicts.

Figures

Figure 1
Figure 1
Flow Diagram of Study Selection
Figure 2
Figure 2
Sensitivity and Specificity of (A) Urine IL18 and (B) Urine NGAL for Diagnosis of ATN
Figure 3
Figure 3
AUC of (A) Urine IL18 and (B) Urine NGAL for Diagnosis of ATN
Figure 4
Figure 4
Sensitivity and Specificity of (A) Urine IL18 and (B) Urine NGAL for Predicting All-Cause Mortality
Figure 5
Figure 5
AUC of (A) Urine IL18 and (B) Urine NGAL for Predicting All-Cause Mortality
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Fagundes C, Barreto R, Guevara M, et al. A modified acute kidney injury classification for diagnosis and risk stratification of impairment of kidney function in cirrhosis. Journal of hepatology. 2013;59(3):474–81. - PubMed
    1. Piano S, Rosi S, Maresio G, et al. Evaluation of the Acute Kidney Injury Network criteria in hospitalized patients with cirrhosis and ascites. Journal of hepatology. 2013;59(3):482–9. - PubMed
    1. Garcia–Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008;48(6):2064–77. - PubMed
    1. Allegretti AS, Ortiz G, Wenger J, et al. Prognosis of Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis: A Prospective Cohort Study. International journal of nephrology. 2015;2015:108139. - PMC - PubMed
    1. Angeli P, Gines P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Gut. 2015;64(4):531–7. - PubMed

MeSH terms