Early Diagnosis and Prognostic Value of Acute Kidney Injury in Critically Ill Patients

Background and objectives: In hospitalized children, acute kidney injury (AKI) remains to be a frequent and serious condition, associated with increased patient mortality and morbidity. Identifying early biomarkers of AKI and patient groups at the risk of developing AKI is of crucial importance in current clinical practice. Specific human protein urinary neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin 18 (uIL-18) levels have been reported to peak specifically at the early stages of AKI before a rise in serum creatinine (sCr). Therefore, the aim of our study was to determine changes in uNGAL and uIL-18 levels among critically ill children and to identify the patient groups at the highest risk of developing AKI. Materials and methods: This single-center prospective observational study included 107 critically ill children aged from 1 month to 18 years, who were treated in the Pediatric Intensive Care Unit (PICU) of Lithuanian University of Health Sciences Hospital Kauno Klinikos from 1 December 2013, to 30 November 2016. The patients were divided into two groups: those who did not develop AKI (Group 1) and those who developed AKI (Group 2). Results: A total of 68 (63.6%) boys and 39 (36.4%) girls were enrolled in the study. The mean age of the patients was 101.30 ± 75.90 months. The mean length of stay in PICU and hospital was 7.91 ± 11.07 and 31.29 ± 39.09 days, respectively. A total of 32 (29.9%) children developed AKI. Of them, 29 (90.6%) cases of AKI were documented within the first three days from admission to hospital. In all cases, AKI was caused by diseases of non-renal origin. There was a significant association between the uNGAL level and AKI between Groups 1 and 2 both on day 1 (p = 0.04) and day 3 (p = 0.018). Differences in uNGAL normalized to creatinine in the urine (uCr) (uNGAL/uCr) between the groups on days 1 and 3 were also statistically significant (p = 0.007 and p = 0.015, respectively). uNGAL was found to be a good prognostic marker. No significant associations between uIL-18 or Uil-18/uCr and development of AKI were found. However, the uIL-18 level of >69.24 pg/mL during the first 24 hours was associated with an eightfold greater risk of AKI progression (OR = 8.33, 95% CI = 1.39-49.87, p = 0.023). The AUC for uIL-18 was 73.4% with a sensitivity of 62.59% and a specificity of 83.3%. Age of <20 months, Pediatric Index of Mortality 2 (PIM2) score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of three and more organ systems, PICU length of stay more than three days, and length of mechanical ventilation of >five days were associated with a greater risk of developing AKI. Conclusions: Significant risk factors for AKI were age of <20 months, PIM2 score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of 3 and more organ systems, PICU length of stay of more than three days, and length of mechanical ventilation of > five days. uNGAL was identified as a good prognostic marker of AKI. On admission to PICU, uNGAL should be measured within the first three days in patients at the risk of developing AKI. The uIL-18 level on the first day was found to be as a biomarker predicting the progression of AKI.