The Outcome of Neutrophil Gelatinase-Associated Lipocalin-Positive Subclinical Acute Kidney Injury

Abstract

Objectives To test the hypothesis that, without diagnostic changes in serum creatinine, increased NGAL levels identify patients with subclinical acute kidney injury (AKI) and, therefore, worse prognosis. Background Neutrophil gelatinase-associated lipocalin (NGAL) detects subclinical AKI hours to days before increases in serum creatinine indicate manifest loss of renal function. Methods We analyzed pooled data from 2,322 patients with cardiorenal syndrome type 1 from ten prospective observational studies of NGAL. We used the terms NGAL(−) or NGAL(+) according to study-specific NGAL cut-off for optimal AKI prediction and the terms sCREA(−) or sCREA(+) to consensus diagnostic increases in serum creatinine defining AKI. A-priori-defined outcomes included need for renal replacement therapy (primary endpoint), hospital mortality, their combination and duration of stay in intensive care and in-hospital. Results Of study patients, 1,296 (55.8%) were NGAL(−)/sCREA(−), 445 (19.2%) NGAL(+)/sCREA(−), 107 (4.6%) NGAL(−)/sCREA(+) and 474 (20.4%) NGAL(+)/sCREA(+). According to the four study groups, there was a stepwise increase in subsequent renal replacement therapy initiation, (NGAL(−)/sCREA(−): 0.0015% vs. NGAL(+)/sCREA(−): 2.5% [odds ratio 16.4, 95% CI 3.6–76.9, P<0.001], NGAL(−)/sCREA(+): 7.5% and NGAL(−)/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 and consistent 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. Conclusions In the absence of diagnostic increases in serum creatinine, NGAL detects patients with subclinical AKI who have an increased risk of adverse outcomes. The concept and definition of AKI may need re-assessment.