Evaluation of Urinary NGAL as a Diagnostic Tool for Acute Kidney Injury in Critically Ill Patients With Infection: An Original Study

Abstract

Background: Acute kidney injury (AKI) is a common complication in critical care patients. The presence of AKI is a marker for poor outcomes such as longer hospitalization durations, more hospital readmissions, and especially, higher mortality rates. Sepsis is one of the major causes of AKI within the intensive care unit (ICU) population. Sepsis-related AKI occurs in approximately 20% of patients, reaching more than 50% in patients with septic shock. The diagnosis of AKI depends on urine output and/or serum creatinine measurements. Unfortunately, serum creatinine is a late and unreliable (insensitive and nonspecific) indicator of AKI. However, biomarkers of renal damage have great potential in facilitating early diagnosis of AKI. Several biomarkers, including urinary neutrophil gelatinase-associated lipocalin (uNGAL), have been used in the early detection of AKI. Objectives: The aim of this study was to evaluate uNGAL for the diagnosis and prognosis of AKI in critical ill patients with infections. Design: Original study (Cohort Prospective Observational). Setting: Study in 2 ICUs of different Brazilian hospitals, in the city of Curitiba: Hospital de Clínicas da Universidade Federal do Paraná and Hospital da Polícia Militar do Paraná, from November 12, 2016 to May 15, 2018. Participants: Critically ill patients with infections, sepsis, or septic shock were selected. The inclusion criteria were patients older than 18 years with infection. They were followed up for 30 days in the analysis of outcomes. We requested that consent forms be signed by all eligible patients or their caregivers. Measurements: The urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels of the patients were measured on 4 consecutive days and was assayed using a chemiluminescent microparticle immunoassay system. The screening time occurred within 72 hours of admission to the ICU. The first urine sample was collected within the first 24 hours of the screening hours. Mortality and AKI were assessed during first 30 days. Methods: clinical and laboratory data, including daily uNGAL levels, were assessed. The AKI stage using the KDIGO criteria was evaluated. Sensitivity, specificity, and the area under the curve-receiver operating characteristic (AUC-ROC) values were calculated to determine the optimal uNGAL level for predicting AKI. Results: We had 38 patients who completed the study during the screening period. The incidence of AKI was 76.3%. The hospitalization period was longer in the group that developed AKI, with 21 days of median (interquartile range [IQR]: 13.5-25); non-AKI group had a median of 13 days (IQR 7-18; P = .019). We found a direct relationship between uNGAL levels and the progression to AKI. Increased values of the biomarker were associated with the worsening of AKI ( P < .05). The cutoff levels of uNGAL that identified patients who would progress to AKI were the following: (d1) >116 ng/mL, (d2) >100 ng/mL, and (d3) 284 ng/mL. The value of the fourth and last measurement was not predictive of patients who would progress to AKI. The median urinary uNGAL was also associated with mortality on Days 1, 3, and 4: d1, P = .039; d3, P = .005; d4, P = .005. The performance of uNGAL in detecting AKI patients (AUC-ROC = 0.881). There were no risk factors other than AKI that could be correlated with increased uNGAL levels on Day 1. Limitations: The study was carried out in 2 centers, having used only 1 biomarker, and our small number of patients were limitations. Conclusion: the uNGAL had an association in its values with the diagnosis and prognosis of patients with severe infections and AKI. We suggest that studies with a greater number of patients could better establish the cutoff values of uNGAL and/or serum NGAL in the identification of infected patients who are at a high risk of developing AKI.