Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatal

Abstract

Acute Kidney Injury (AKI) is one of the most commonly associated complications with neonatal infections (NI), as well as with sepsis. AKI consists of a sudden reduction in renal function and can be fatal, being considered one of the main causes of morbidity and mortality in premature neonates. Renal impairment in sepsis is due to the mechanism of renal ischemia/reperfusion, which is described as the main cause of AKI. Additionally, reduced renal blood flow and hypoperfusion result in low oxygen demands that induce injury to tubular epithelial cells, apoptosis, and acute tubular necrosis in cases of prolonged hypoperfusion. The diagnosis of AKI is clinically evident by an increase in serum creatinine levels, a criterion that is imprecise and late, as its levels decrease after a loss of 50% of renal function and reflect maternal levels during the first 48 hours of life. The use of innovative biomarkers in the early diagnosis of AKI has been reported in the literature, including urinary cystatin-C (uCysC) and neutrophil gelatinase-associated

lipocalin (uNGAL). It is noteworthy that uCysC and uNGAL, in addition to being non- invasive, are not influenced by muscle mass, sex, age, or maternal levels. The present

study aimed to evaluate innovative biomarkers of renal damage, uNGAL and uCysC, as

predictors in premature neonates diagnosed with sepsis and NI. This was a cross- sectional, descriptive, and observational study with 64 premature neonates, including 20

with NI, 20 with neonatal sepsis (NS), and 20 controls, at the Assis Chateaubriand School Maternity Hospital (MEAC), Fortaleza-Ceará. The diagnosis of NI and sepsis was made using MEAC clinical protocols. The anthropometric, clinical, and laboratory variables of the neonates and the clinical variables of the mothers were obtained from medical records. The analysis of uCysC and uNGAL was performed using an enzyme-linked immunosorbent assay (ELISA) methodology. Statistical significance was set at p<0.05. A total of 47 (73.4%) were male and mostly appropriate for gestational age (AGA). The evaluation of AKI by neonatal KDIGO demonstrated a total of 11 (17.2%), with 4 (20%) with NI and 7 (35%) with sepsis. The mean values of uCysC were 872.29 ng/ml-Cr in the NI group, 3058.93 ng/ml-Cr in the sepsis group, and 152.19 ng/ml-Cr in the control group. The mean values of uNGAL were 42.1 ng/ml-Cr in the NI group, 43.95 ng/ml-Cr in the sepsis group, and 12.5 ng/ml-Cr in the control group. There was a significant difference in uCysC and uNGAL levels between the NI and sepsis groups compared to the control group. uCysC was associated with the following clinical variables: respiratory complications, respiratory distress syndrome, mechanical ventilation, and orotracheal intubation. uNGAL levels were associated with variables such as hospitalization time >30 days, AKI by nKDIGO, mechanical ventilation, intubation, resuscitation in the delivery room, and respiratory distress/SDR. It is concluded that uCysC and uNGAL are promising biomarkers in the early diagnosis of renal damage in premature neonates with NI and sepsis.