Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Complications and Mortality in Patients Undergoing Non-Cardiac Major Surgery

Abstract

Introduction: We tested the hypothesis that urinary and serum neutrophil gelatinase-associated lipocalins (NGAL) early after non-cardiac major surgery predict postoperative acute kidney injury (AKI), complications and mortality. Methods: We studied 74 patients undergoing orthopedic, vascular and abdominal surgery lasting ≧2 h. NGAL was measured in preoperative, as well as 2- and 6-hour postoperative samples. The primary outcome was AKI. Secondary outcome was postoperative infection and death. Results: 10 patients (13.5%) developed AKI, 19 (26%) reached secondary outcomes, of whom 5 (7%) died. Serum NGAL was significantly higher in patients with diabetes and chronic kidney disease (CKD). No significant correlation was detected between serum or urine NGAL and subsequent development of AKI. Urine NGAL at 6 h and serum NGAL at 2 and 6 h were strongly correlated with postoperative infection and death (p = 0.004, p = 0.013 and p = 0.001, respectively). Conclusions: Our data suggest that in the general surgical population, NGAL could serve as a potent early biomarker for postoperative infection, and that the presence of CKD and diabetes mellitus is associated with higher levels of NGAL and may influence its predictive value.

Using NGAL as an Early Diagnostic Test of Acute Kidney Injury

“…The significant limitations of sNGAL measurement as a structural marker of AKI are increased concentrations in patients with lower respiratory tract infections, 17 systemic infections/sepsis, 18 thrombocythemia, polycythemia, 19 and cancers, 20 while uNGAL increases in patients with urinary tract infections 21 as well being above individual baselines in CKDs. 22 The implications of these limitations include false positive or negative results which could lead to failure of timely diagnosis, which of course is the stated purpose of using NGAL as a biomarker for AKI, demonstrating that the addition of quantitative measurement does not add value to clinical decision processes. The increased levels of NGAL in other disease processes also have the potential of causing misdiagnosis of AKI where none exists, as well as masking and delaying the detection and treatment of other pathologies.…”

“…Noncardiac major surgery 93 ng/L ± 38 (serum) Shavit et al 22 Noncardiac major surgery 83 ng/L ± 234 (urine) Shavit et al 22 Critically ill children 14.2 ng/mL ± 27 (urine) Zappitelli et al 27 Critically ill adults 48.1 ng/mL (urine), IQR(12.7-179.3)…”

“…As was comprehensively detailed in the meta-analysis by Haase et al 31 the sensitivity and specificity vary at widely different cutoff values. Confounding the sensitivity and specificity of NGAL even further, different patient populations such as premature infants 32 and those with existing risk factors for or actual CKD, 22 it is demonstrated that the sensitivity, specificity, and cutoff values for NGAL to detect AKI are specific to each patient population. It seems that while NGAL can add quantitative data, these data do not add anything to the clinical decision processes.…”

“…34 Additionally, the use of NGAL may also be viable only in the absence of major risk factors or CKD. 22 The increasing NGAL levels with CKD stage is another factor limiting usefulness in differentiating between AKI, acute-on-chronic, and CKD in patients with an unknown etiology of kidney injury and previously increased serum creatinine concentrations that went undetected prior to a suspected recent injury. 35 …”

Neutrophil gelatinase-associated lipocalin and albuminuria as predictors of acute kidney injury in patients treated with goal-directed haemodynamic therapy after major abdominal surgery

“…26 Although our results reached statistical significance, our findings will need to be validated in a larger cohort of patients, including those undergoing other surgical procedures. In this study, we found NGAL rose significantly following surgery in all groups.…”