Diagnostic and prognostic performance of urinary neutrophil gelatinase‐associated lipocalin in patients with cirrhosis and acute kidney injury

Abstract

Background and Aims: Acute kidney injury (AKI) commonly occurs in patients with decompensated cirrhosis. Urinary neutrophil gelatinaseassociated lipocalin (uNGAL) could help discriminate between different etiologies of AKI. The aim of this study was to investigate the use of uNGAL in (1) the differential diagnosis of AKI, (2) predicting the response to terlipressin and albumin in patients with hepatorenal syndrome-AKI (HRS-AKI), and (3) predicting in-hospital mortality in patients with AKI.Approach and Results: One hundred sixty-two consecutive patients with cirrhosis and AKI were included from 2015 to 2020 and followed until transplant, death, or 90 days. Standard urinary markers and uNGAL were measured. Data on treatment, type, and resolution of AKI were collected. Thirty-five patients (21.6%) had prerenal AKI, 64 (39.5%) HRS-AKI, 27 (16.7%) acute tubular necrosis-AKI (ATN-AKI), and 36 (22.2%) a mixed form of AKI. Mean values of uNGAL were significantly higher in ATN-AKI than in other types of AKI (1162 ng/ml [95% CI 423-2105 ng/ml] vs. 109 ng/ml [95% CI 52-192 ng/ ml]; p < 0.001). uNGAL showed a high discrimination ability in predicting ATN-AKI (area under the receiver operating characteristic curve, 0.854; 95% CI 0.767-0.941; p < 0.001). The best-performing threshold was found to be 220 ng/ml (sensitivity, 89%; specificity, 78%). The same threshold was independently associated with a higher risk of nonresponse (adjusted OR [aOR],

Hepatorenal syndrome: Current concepts and future perspectives

“…64,65 For example, in 162 patients with AKI and cirrhosis, not only was urinary NGAL an adequate biomarker in the differential diagnosis of AKI, but it also predicted the response to terlipressin and albumin in patients with HRS-AKI, and was also an independent predictor of in-hospital mortality. 64 Similarly, in a study consisting of 213 US hospitalized patients with decompensated cirrhosis, not only did urinary NGAL differentiate the type of AKI in cirrhosis, but also significantly predicted 90-day transplant-free survival, and outperformed Model for End-Stage Liver Disease score in terms of survival prediction. 65 Although the most ideal biomarker would be one that distinguishes structural from functional AKI, but in reality, no biomarkers to date perform optimally in the differential diagnosis of AKI in patients with cirrhosis.…”

“…98 For example, in two cohorts of patients with cirrhosis listed for LT, one with and one without HRS-AKI, response to terlipressin and albumin reduced the need for KRT after LT, and also reduced the risk of CKD at 1 year after LT. 98 Factors associated with lower response to terlipressin and albumin include higher baseline serum creatinine, urinary NGAL and serum bilirubin, lower increases in arterial pressure, presence of systemic inflammatory response syndrome, and more severe acute on chronic liver failure grade. 15,64,[99][100][101] Common side effects of terlipressin include diarrhea and abdominal pain, which are reported in around 10-20% of patients. More serious side effects are related to vasoconstriction with a risk of myocardial infarction and intestinal ischemia, with a rate of 2-13%.…”

Terlipressin for hepatorenal syndrome: The practical choice for clinicians

“…[3] Additionally, high fractional excretion of sodium may help rule out HRS, [4] and urinary neutrophil gelatinase-associated lipocalin > 220 ng/mL is predictive of acute tubular necrosis and nonresponse to terlipressin. [5] Figure 1 proposes a diagnostic framework for diagnosing HRS in patients with cirrhosis and ascites. For decades, terlipressin has been used in the European Union and other regions across the world for HRS, but it did not obtain the US Food and Drug Administration (FDA) approval until 2022.…”

“…In particular, fractional excretion of urea <21% is more predictive of HRS than prerenal azotemia, whereas values <28% are more predictive of HRS than nonHRS 3 . Additionally, high fractional excretion of sodium may help rule out HRS, 4 and urinary neutrophil gelatinase–associated lipocalin >220 ng/mL is predictive of acute tubular necrosis and nonresponse to terlipressin 5 Figure 1. proposes a diagnostic framework for diagnosing HRS in patients with cirrhosis and ascites.…”

NGAL in AKI and cirrhosis—Ready for prime time?

“…[2] In their retrospective cohort study, Gambino and Piano et al assessed 90-day outcomes of 162 consecutive adult patients who were hospitalized with AKI and cirrhosis at a single center in Italy. [3] Their aim was to assess urinary NGAL's performance in (a) differentiating ATN from functional AKI in cirrhosis (i.e., prerenal AKI and HRS-AKI), (b) predicting shortterm mortality, and (c) predicting response to terlipressin treatment among those with HRS-AKI. Urinary NGAL was used as part of routine clinical care during the study period, and their population demographics were similar to those published in prior studies, [4,5] making this study an excellent snapshot of the "real clinical practice" performance of a test like NGAL.…”