The association of neutrophil gelatinase-associated lipocalin with inflammation, organ dysfunction and survival in surgical sepsis
Authors: Bojic S1, Kotur-Stevuljevic J2, Memon L1 Toskovic B1, Simic-Ogrizovic S3
1CHC Bezanijska Kosa, Belgrade, Serbia; 2Faculty of Pharmacy, Belgrade University, Serbia; 3Medical School, Belgrade University, Belgrade, Serbia
Background and Goal of Study: Neutrophil gelatinase-associated lipocalin (NGAL), an established biomarker of acute kidney  injury (AKI), is also an emerging biomarker of inflammation. Systemic inflammation has a pivotal role in the pathogenesis of organ dysfunction in sepsis. We aimed to explore, for the first time, the association of NGAL with inflammation, organ dysfunction and survival in surgical sepsis.
Materials and Methods: This prospective, observational study included 153 major abdominal surgery patients divided into sepsis group (n = 53), operated controls (n = 50) and not-operated controls (n = 50), matched by age, gender, comorbidities and type of surgery. Occurrence of AKI, use of renal replacement therapy (RRT), vasopressors/inotropes, mechanical ventilation and 28-day survival were noted. Blood and urine samples from the patients with sepsis were collected daily during 96 h following admission to intensive care unit (ICU) and once from the controls. We measured serum (s-) and urine (u-) NGAL, white blood cell (WBC) count, C-reactive protein (CRP), procalcitonin (PCT), lactate, total bilirubin, platelet count and international normalized ratio (INR). Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were calculated. 
Results and Discussion: Significantly higher values of both sNGAL and uNGAL were observed at all time points in patients with sepsis compared to both control groups as well as in operated controls compared to not-operated controls. During 96 h following ICU admission, higher NGAL levels  were found in septic patients with AKI (PsNGAL = 0.008, PuNGAL = 0.004), on RRT (PsNGAL = 0.032, PuNGAL = 0.042) and vasopressors/inotropes (PsNGAL = 0.001, PuNGAL < 0.001) but not in mechanicaly ventilated (PsNGAL = 0.908, PuNGAL = 0.968).  SNGAL correlated with WBC count, CRP, lactate and bilirubin levels (Tau-b = 0.136, 0.320, 0.378 and 0.183, respectively) but not  with PCT, platelet count and INR. NGAL correlated with APACHE II (Tau-bsNGAL = 0.319, Tau-buNGAL = 0.432) and SOFA (Tau-bsNGAL = 0.246, Tau-buNGAL = 0.374) scores.  Higher levels of this biomarker were associated with shorter 28-day survival (Log-rank: PsNGAL = 0.007, PuNGAL < 0.001).
Conclusions: Higher NGAL levels were associated with inflammation, AKI, RRT, use of vasopresors/inotropes, higher lactate and bilirubin levels as well as with poor survival in surgical sepsis.