Urinary Neutrophil Gelatinase-Associated Lipocalin Predicts Mortality and Identifies Acute Kidney Injury in Cirrhosis

Abstract

Background Kidney failure predicts mortality in patients with cirrhosis. Identification of kidney failure etiology and recognition of those at the highest mortality risk remains a challenge. Aims We hypothesized that urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) predicts mortality and identifies hepatorenal syndrome (HRS) in patients with cirrhosis. Methods Prospectively enrolled patients with cirrhosis were investigated by uNGAL immunoblot upon hospital admission. Kidney failure type was determined blinded to NGAL measurements. Results One hundred and eighteen patients were enrolled. Fifty-two (44%) patients had normal kidney function, 14 (12%) stable chronic kidney disease, 17 (14%) prerenal azotemia, 20 (17%) HRS, and 15 (13%) intrinsic acute kidney injury (iAKI). Patients with HRS had uNGAL levels intermediate between prerenal azotemia [median (IQR) 105 (27.5–387.5) v. 20 (15–45) ng/ml, p=0.004] and iAKI [325 (100–700), p<0.001]. Fifteen (13%) patients died. In unadjusted analysis, uNGAL predicted inpatient mortality (OR 2.00, 95% CI 1.36–2.94) and mortality or liver transplantation (OR 2.01, 95% CI 1.42–2.85). In multiple regression models, uNGAL>110 ng/ml (OR 6.05, 95% CI 1.35–27.2) and HRS (OR 6.71, 95% CI 1.76–25.5) independently predicted mortality, adjusting for age and serum creatinine>1.5 mg/dL. Conclusions uNGAL strongly predicts short term inpatient mortality in both unadjusted and adjusted models. Patients with HRS may have uNGAL levels intermediate between those with prerenal azotemia and iAKI. Further studies are needed to determine if uNGAL can improve discrimination of HRS from other types of acute kidney injury and predict short- and long-term cirrhosis outcomes.

Urinary Biomarkers and Progression of AKI in Patients with Cirrhosis

“…Among the most promising are neutrophil gelatinase-associated lipocalin (NGAL), IL-18, kidney injury molecule-1 (KIM-1), and liver-type fatty acid-binding protein (L-FABP). Although NGAL has been studied for early detection of AKI after liver transplantation (18,19) and for differential diagnosis of AKI in cirrhosis (20,21), few studies have evaluated these biomarkers for prognosis in patients with cirrhosis and AKI (20,21). With a unique mix of functional (HRS) and structural disease (ATN and GN), the association in cirrhosis between tubular injury biomarker levels and outcomes is unclear.…”

Kidney Biomarkers in Hepatorenal Syndrome

“…Human studies suggest that NGAL measurements either in urine and serum may differentiate acute tubular necrosis from type 1 HRS, pre-renal azotemia or chronic kidney disease [11]. Two recent studies suggest that elevated urinary NGAL is predictive of early mortality in cirrhotic patients with AKI [12,13]. However, NGAL lacks specificity as it is also elevated in other acute and chronic inflammatory conditions.…”

Renal dysfunction in patients with cirrhosis: Where do we stand?

“…Many studies in several clinical situations [39][40][41] have underlined that the NGAL increased two hours after the induction of AKI, before of the sCr elevation. In cirrhotic patients, preliminary studies have reported that NGAL levels were higher in those with HRS [42] compared to those without renal disease; NGAL was associated with the prediction of short-term mortality [43,44] and it could be used for differentiation of prerenal azotemia, acute tubular necrosis and HRS [45] . Urinary NGAL has been found to be 20 ng/mL in healthy population and in prerenal azotemia, 105 ng/mL in HRS, 325 ng/mL in AKI and 50 ng/mL in CKD [44] .…”