Neutrophil Gelatinase‐Associated Lipocalin for Assessment of Acute Kidney Injury in Cirrhosis: A Prospective Study

Abstract

Kidney biomarkers appear to be useful in differential diagnosis between acute tubular necrosis (ATN) and other types of acute kidney injury (AKI) in cirrhosis, particularly hepatorenal syndrome (HRS-AKI). Distinction is important because treatment is different. However, kidney biomarkers are still not used in clinical practice. The aim of the current study was to investigate the accuracy of several biomarkers in differential diagnosis of AKI and in predicting kidney outcome and patient survival. This was a prospective study of 320 consecutive cases of AKI in patients hospitalized for decompensated cirrhosis. Evaluation of AKI was made with a diagnostic algorithm that included identification and removal/treatment of precipitating factors and albumin administration (1 g/kg for 2 days) to patients with AKI stage 1B or greater. Urinary neutrophil gelatinase-associated lipocalin (NGAL), monomeric NGAL (mNGAL), interleukin-18, and standard biomarkers were measured at diagnosis and on days 3, 7, and 14. Of the 320 cases, 153 were hypovolemia-induced AKI (48%), 93 were HRS-AKI (29%), 39 were ATN (12%), and 35 were due to miscellaneous causes (11%). Among all biomarkers, urinary NGAL measured at day 3 had the greatest accuracy for differential diagnosis between ATN and other types of AKI (area under the receiver operating characteristic curve, 0.87; 95% confidence interval, 0.78-0.95). The cutoff with the best predictive accuracy for ATN diagnosis was 220 µg/g creatinine. Progression of AKI during hospitalization was associated with persistently high NGAL levels, and NGAL was an independent predictive factor of AKI progression. Likewise, NGAL was also an independent predictive factor of 28-day mortality together with Model for End-Stage Liver Disease score. Conclusion: These results support the use of NGAL in clinical practice within the context of a diagnostic algorithm for differential diagnosis of AKI and outcome prediction in cirrhosis. (Hepatology 2019;70:319-333).A cute kidney injury (AKI) is a common complication of patients with advanced cirrhosis hospitalized for an acute decompensation. (1)(2)(3)(4)(5)(6) Importantly, the occurrence of AKI impairs prognosis. The 3-month probability of mortality after AKI is very high, ranging from 28% to 47%. (3)(4)(5)(6)(7)(8) Mortality

News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document

“…studies show, as previously discussed, that high levels of multiple biomarkers in the urine, particularly NGAL, are indicative of the presence of ATN. [40][41][42][43][44][45] However, they also demonstrate that in HRS, as defined in Box 1, these biomarkers are also increased, albeit not as in patients with ATN but more than in patients with prerenal AKI. 41,44 Based on this evidence, the idea that HRS is purely a ''functional" renal failure appears unsustainable.…”

“…Absolute increase in sCr ≥0.3 mg/dl within 48 hours AKI defined as a percent increase in sCr ≥50% in the last 7 days (but it is possible to use as baseline sCr a value within the last 3 months) to be 220 lg/g of creatinine. 45 Most patients with ATN-AKI (86%) had values of urinary NGAL above this threshold, whereas the majority of patients with HRS-AKI or prerenal AKI (88% and 93%, respectively) had values below it. 45 However, none of these studies included a gold standard (histology) for the diagnosis of ATN and thus, a diagnosis of ATN remains difficult to establish in patients with cirrhosis and AKI; indeed, HRS and ATN may be considered a continuum rather than two distinct entities.…”

“…45 Most patients with ATN-AKI (86%) had values of urinary NGAL above this threshold, whereas the majority of patients with HRS-AKI or prerenal AKI (88% and 93%, respectively) had values below it. 45 However, none of these studies included a gold standard (histology) for the diagnosis of ATN and thus, a diagnosis of ATN remains difficult to establish in patients with cirrhosis and AKI; indeed, HRS and ATN may be considered a continuum rather than two distinct entities. While NGAL and other biomarkers of structural injury hold great promise for distinguishing between HRS from ATN, the test is not clinically available in much of the world.…”

“…Nevertheless, the presence of increased levels of some tubular biomarkers in patients with HRS-AKI may suggest that there is a continuum from HRS to ATN. 44 Across the majority of studies [42][43][44][45] levels of NGAL, the most investigated biomarker, have been remarkably consistent in patients diagnosed with HRS, raising the possibility of NGAL as an objective test to distinguish primarily functional AKI from structural AKI in patients with cirrhosis 45 and guide decisions regarding vasoconstrictor therapy. 45 More specifically, the cut-off with the best predictive accuracy for ATN diagnosis was found Box 1.…”

“…Regarding the second question, although a high urinary level of NGAL is an independent predictor of AKI progression, no difference in NGAL levels was found in patients with HRS-1 between responders and non-responders to terlipressin and albumin. 45 Finally, among the factors that are not related to therapeutic agents, the pretreatment level of sCr should also be considered, as previously discussed. 33,34 Factors related to the agents used Type of vasoconstrictor Three types of vasoconstrictors are currently available for the treatment of HRS: terlipressin, noradrenaline and the combination of midodrine + octreotide.…”