Using Urinary NGAL as a Biomarker for AKI in Cirrhosis

Liver cirrhosis. Computer illustration and light micrograph of a section through a human liver with cirrhosis-associated hepatocellular nodules.
A team of investigators conducted a prospective cohort study to validate NGAL as a diagnostic and prognostic tool for AKI in cirrhosis within North America.

Urinary neutrophil gelatinase-associated lipocalin (NGAL) may be a useful biomarker in differentiating acute tubular necrosis (ATN) from other types of acute kidney injuries (AKIs) in patients with cirrhosis, according to study results published in Clinical and Translational Gastroenterology. Results also suggested that NGAL may be useful in predicting short-term mortality and AKI stage progression, especially when used in tandem with existing models (ie, Model for End-Stage Liver Disease [MELD]).

Although NGAL has been shown to differentiate ATN from hepatorenal syndrome and other types of AKIs, NGAL is not currently available in clinical practice in North America. A team of investigators therefore conducted a prospective cohort study to validate NGAL as a diagnostic and prognostic tool for AKI in cirrhosis within North America.

Nonconsecutive adult patients with decompensated cirrhosis and AKI who were admitted to Massachusetts General Hospital from 2013 to 2019 were enrolled and monitored prospectively for 90 days following admission. A population of patients with complications of cirrhosis without AKI were included as a reference group.

A total of 213 patients were included in the analysis: 161 patients with AKI and 52 reference patients. Of the patients with AKI, 57 had prerenal AKI, 55 patients had hepatorenal syndrome, and 49 patients had ATN. At the time of enrollment, the median serum creatinine level was 2.0 mg/dL. The median MELD score was 23, the median Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure (CLIF-C ACLF) score was 45, and the median time for admission to enrollment was 3 days. Following enrollment, 34 patients in the total cohort underwent liver transplantation.

At enrollment, urinary NGAL levels were the lowest among patients with prerenal AKI. Urinary NGAL distinguished ATN from non-ATN kidney injury at an optimal cutpoint of 244 µg/g with a C statistic of 0.762, 71% sensitivity, 76% specificity, 56% positive predictive value, and 86% negative predictive value.

By the end of the 90-day study period, 33% of patients died. Univariate analysis suggested that older age, higher MELD score, higher CLIF-C ACLF score, presence of hepatocellular carcinoma, and multiple laboratory abnormalities were significantly associated with death by 90 days. Compared with prerenal and no AKI, ATN and hepatorenal syndrome were also linked with higher mortality rates, as was a higher median NGAL.

Compared with MELD score by C statistic, net reclassification index, and integrated discrimination increment, NGAL significantly outperformed other measures in predicting 90-day transplant-free survival.

“[U]rinary NGAL may differentiate the type of AKI in cirrhosis and may improve prediction of short-term mortality,” the authors wrote. “It holds immediate clinical potential to immediately affect management of AKI in cirrhosis and warrants further investigation in this population,” the investigators concluded.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Allegretti AS, Parada XV, Endres P, et al for the HRS-HARMONY study. Urinary NGAL as a diagnostic and prognostic marker for acute kidney injury in cirrhosis: a prospective study. Clin Transl Gastroenterol. 2021;12(5):e00359. doi:10.14309/ctg.0000000000000359