The Outcome of Neutrophil Gelatinase-Associated Lipocalin-Positive Subclinical Acute Kidney Injury: A Multicenter Pooled Analysis of Prospective Studies

Study Questions:

Do increased levels of neutrophil gelatinase-associated lipocalin (NGAL) reflect subclinical renal injury and predict adverse outcomes?


Pooled data including 2,322 critically ill patients with predominantly cardiorenal syndrome from 10 prospective observational studies of NGAL were analyzed. The terms NGAL(-) or NGAL(+) were defined as a study-specific NGAL cutoff for optimal acute kidney injury (AKI) prediction and the terms sCREA(-) or sCREA(+) according to consensus diagnostic increases in serum creatinine defining AKI. Outcomes included need for renal replacement therapy (primary endpoint), hospital mortality, their combination, and duration of stay in intensive care and in-hospital.


A total of 1,296 (55.8%) subjects were NGAL(-)/sCREA(-), 445 (19.2%) were NGAL(+)/sCREA(-), 107 (4.6%) were NGAL(-)/sCREA(+), and 474 (20.4%) were NGAL(+)/sCREA(+). Among the four study groups, there was a stepwise increase in subsequent renal replacement therapy initiation—NGAL(-)/sCREA(-): 0.0015% versus NGAL(+)/sCREA(-): 2.5% (odds ratio, 16.4; p < 0.001), NGAL(-)/sCREA(+): 7.5%, and GAL(+)/sCREA(+): 8.0%, respectively, hospital mortality (4.8%, 12.4%, 8.4%, 14.7%, respectively) and their combination (four-group comparisons: all p < 0.001). There was a similar progressive increase in median number of intensive care and in-hospital days with increasing biomarker positivity: NGAL(-)/sCREA(-): 4.2 and 8.8 days; NGAL(+)/sCREA(-): 7.1 and 17.0 days; NGAL(-)/sCREA(+): 6.5 and 17.8 days; NGAL(+)/sCREA(+): 9.0 and 21.9 days; four-group comparisons: p = 0.003 and p = 0.040, respectively. Urine and plasma NGAL indicated a similar outcome pattern.


The authors concluded that in the absence of diagnostic increases in serum creatinine, NGAL detects patients with likely subclinical AKI who have an increased risk of adverse outcomes.


NGAL is released from the distal nephron following injury and has been shown to detect AKI days before loss of renal function is detected using serum creatinine levels. Similar to the case with cardiac troponins for detecting myocyte injury, there are likely to be informative biomarkers of renal injury that are elevated well before changes in creatinine clearance are detected. Biomarkers such as NGAL could be useful in guiding management of cardiac patients after contrast exposure or in patients with renal hypoperfusion due to heart failure. In patients with positive biomarkers, early therapeutic interventions designed to limit kidney damage could be instituted well before the rise in creatinine is observed.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Chronic Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Hospital Mortality, Biological Markers, Cardio-Renal Syndrome, Acute Kidney Injury, Kidney, United States

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