Urinary NGAL as a Diagnostic and Prognostic Marker for Acute Kidney Injury in Cirrhosis: A Prospective Study

Abstract

Introduction: Urinary neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in differentiating acute tubular necrosis (ATN) from other types of acute kidney injuries (AKIs) in cirrhosis, particularly hepatorenal syndrome (HRS). However, NGAL is not currently available in clinical practice in North America.

Methods: Urinary NGAL was measured in a prospective cohort of 213 US hospitalized patients with decompensated cirrhosis (161 with AKI and 52 reference patients without AKI). NGAL was assessed for its ability to discriminate ATN from non-ATN AKI and to predict 90-day outcomes.

Results: Among patients with AKI, 57 (35%) had prerenal AKI, 55 (34%) had HRS, and 49 (30%) had ATN, with a median serum creatinine of 2.0 (interquartile range 1.5, 3.0) mg/dL at enrollment. At an optimal cutpoint of 244 μg/g creatinine, NGAL distinguished ATN (344 [132, 1,429] μg/g creatinine) from prerenal AKI (45 [0, 154] μg/g) or HRS (110 [50, 393] μg/g; P < 0.001), with a C statistic of 0.762 (95% confidence interval 0.682, 0.842). By 90 days, 71 of 213 patients (33%) died. Higher median NGAL was associated with death (159 [50, 865] vs 58 [0, 191] μg/g; P < 0.001). In adjusted and unadjusted analysis, NGAL significantly predicted 90-day transplant-free survival (P < 0.05 for all Cox models) and outperformed Model for End-Stage Liver Disease score by C statistic (0.697 vs 0.686; P = 0.04), net reclassification index (37%; P = 0.008), and integrated discrimination increment (2.7%; P = 0.02).

Discussion: NGAL differentiates the type of AKI in cirrhosis and may improve prediction of mortality; therefore, it holds potential to affect management of AKI in cirrhosis.

Figure 1.

Ninety-day probability of transplant-free survival by urinary NGAL (μg/g creatinine). Patients were divided by NGAL tertile at study enrollment (P < 0.001). NGAL, neutrophil gelatinase-associated lipocalin.

Figure 2.

Forest plots of urinary NGAL's hazard ratios for 90-day transplant-free mortality. HRs are presented with 95% CIs. Model 1: adjusted for age and MELD score; model 2: adjusted for age, MELD score, and presence of infection; and model 3: excluding 18 patients with hepatocellular carcinoma. AKI, acute kidney injury; CI, confidence interval; CLIF-C ACLF, Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score; HR, hazard ratio; MELD, Model for End-Stage Liver Disease.

Figure 3.

Relationship between MELD score and 28-day transplant-free mortality, adjusted for age and presence of infection, categorized by quartiles of urinary NGAL (μg/g creatinine). MELD, Model For End-Stage Liver Disease; NGAL, neutrophil gelatinase-associated lipocalin.

Figure 4.

Time course of median urinary NGAL (μg/g creatinine) at study enrollment, day 5, and day 30, classified by the type of AKI. AKI, acute kidney injury; NGAL, neutrophil gelatinase-associated lipocalin.