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.

Snapshots of nascent RNA reveal cell- and stimulus-specific responses to acute kidney injury

“…Increasing doses of ischemia (0, 5, 20, 30, 40 minutes of arterial clamping) increased urine Ngal and Kim-1 as much as 70- and 130-fold, respectively. These data are consistent with both the Ngal-reporter mouse ( 22 ) and human cohorts in emergency departments ( 23 , 34 ) and in other settings ( 14 , 18 , 24 ).…”

“…In addition, because principal and intercalated cells are present in limited numbers (only 2%–3% of total kidney cells), the collecting duct provides a test of the method’s sensitivity. Finally, the particularly rapid expression of the biomarker Ngal ( Lcn2 ) in response to ischemia but not in response to volume depletion ( 14 , 18 , 21 – 24 ) suggests that a kinetically sensitive RNA-labeling method may be particularly useful to distinguish stimulus-specific and cell-specific responses in collecting ducts. Thiouracil tagging provides a unique tool to identify time-dependent transcriptomic profiles in vivo.…”

Response to Weng

“…In particular, NGAL seems to hold greater prognostic significance at higher model for end-stage liver disease scores. We confirmed both of these observations in our study ( 4 ), which we believe contributes to the literature by increasing the generalizability of these results through an American cohort.…”

Comment on “Urinary NGAL as a Diagnostic and Prognostic Marker for Acute Kidney Injury in Cirrhosis”

“…The major concern is the difficulty to make a differential diagnosis among prerenal AKI, ATN-AKI, and HRS-AKI in patients with decompensated cirrhosis. For example, infection is a common precipitating event causing HRS and was present in 19.3% patients with prerenal AKI in the study ( 1 ). As infection must be treated, it is not clear in at least some of these patients that the resolution of AKI was attributed to volume administration or the resolution of infections.…”

“…We read with interest the study by Allegretti et al recently published in Clinical and Translational Gastroenterology regarding the use of urinary neutrophil gelatinase-associated lipocalin (NGAL) in discerning the phenotypes of acute kidney injury (AKI) and predicting the short-term outcome in patients with decompensated cirrhosis ( 1 ). This prospective study demonstrated that urinary NGAL can differentiate acute tubular necrosis (ATN)-AKI from prerenal and hepatorenal syndrome (HRS)-AKI at an optimal cut point.…”