Urinary Concentration of Renal Biomarkers in Healthy Term Neonates: Gender Differences in GST-pi Excretion.

BACKGROUND Serum creatinine, the criterion standard in assessment of renal function, is not reliable for the neonatal period because of its dependence on renal immaturity and maternal creatinine levels. Thus, it is important to study other biomarkers of renal function in neonates. The present study aimed to measure the urinary concentration of renal biomarkers: calbindin, clusterin, GST-pi (glutathione-S-transferase-alpha), KIM-1 (kidney injury molecule 1), MCP-1 (monocyte chemoattractant protein-1), and B2M (beta 2-microglobulin) in healthy term neonates. MATERIAL AND METHODS In the study, we included 80 healthy term neonates - 40 females and 40 males. We collected the neonates' urine on their first day of life. Urinary concentrations of calbindin, clusterin, KIM-1, MCP-1, and B2M were assessed using an immunoassay for kidney toxicology research. Because dilution of the urine affects the concentrations of urinary biomarkers, we normalized them to the concentration of urinary creatinine (Cr) and present them as biomarker/Cr ratios. RESULTS We obtained the following values of the assessed biomarker/Cr ratios (median [Q1-Q3]): calbindin/Cr.: 197.04 (56.25-595.17), KIM-1/Cr: 0.09 (0.04-0.18), MCP-1/Cr: 0.05 (0.02-0.14), B2M/Cr: 126.12 (19.03-342.48), GST-pi/Cr in boys: 1.28 (0.46-3.77), GST-pi/Cr in girls: 8.66 (2.51-27.82), clusterin/Cr: 4.55 (1.79-12.97) ng/mg Cr. CONCLUSIONS We showed the urinary levels of calbindin, clusterin, GST-pi, KIM-1, MCP-1, B2M in white, West Slavic, healthy term neonates. We found that in there is an association between female sex and a higher urinary GST-pi excretion, but urinary excretion of calbindin, clusterin, KIM-1, MCP-1, and B2M is sex-independent. The urinary levels of the assessed biomarkers do not depend on the method of delivery.

Causes of Death in Neonates, Infants, Children, and Adolescents at the University Children's Clinical Hospital of Bialystok Between 2018 and 2021.

BACKGROUND Monitoring of mortality rate and causes of death in pediatric hospitals is required in Poland. This study is aimed to evaluate the causes of death in neonates, infants, children, and adolescents obtained from the medical records of the University Children's Clinical Hospital (UCCH) of Bialystok between 2018 and 2021. MATERIAL AND METHODS This was an observational, cross-sectional study. Medical records of 59 patients (12 neonates, 17 infants, 14 children, 16 adolescents) who died in the UCCH of Bialystok in 2018-2021 were analyzed. The records included personal data, medical history, and causes of death. RESULTS Between 2018 and 2021, the leading death causes were congenital malformations, deformations, and chromosomal abnormalities (25.42%, N=15) and conditions originating in the perinatal period (11.86%, N=7). The leading death causes in each age group were: in neonates - congenital malformations, deformations, and chromosomal abnormalities (50%, N=6), in infants -conditions originating in the perinatal period (29.41%, N=5), in children - diseases of the respiratory system (30.77%, N=4), and in teenagers - external causes of morbidity (31%, N=5). Before the COVID-19 pandemic (2018-2019), the leading death causes were congenital malformations, deformations, and chromosomal abnormalities (20.69%, N=6) and conditions originating in the perinatal period (20.69%, N=6). During the COVID-19 pandemic (2020-2021), congenital malformations, deformations, and chromosomal abnormalities (26.67%, N=8) and COVID-19 (10.00%, N=3) were the most common death causes. CONCLUSIONS Leading death causes varied among age groups. The COVID-19 pandemic had an impact on pediatric causes of death and changed their distribution. The results of this analysis should be discussed and conclusions should improve the quality of pediatric care.

Urinary levels of kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) in children and adolescents with hyperuricemia.

PURPOSE: Hyperuricemia may lead to silent tissue damage and increase the risk of some diseases, including kidney diseases. Increased serum uric acid concentration induces inflammatory pathways and promotes kidney damage. This study aimed to determine whether hyperuricemia influences the levels of urinary kidney injury markers in children and adolescents with hyperuricemia, assessed by the urinary concentrations of interleukin-18, a biomarker of inflammation, and kidney injury molecule-1 (KIM-1), a biomarker of kidney injury. MATERIAL AND METHODS: The study included 73 children and adolescents (32 males and 41 females) aged 2-18 years. They were divided into two groups: hyperuricemia (HU) group (n â€‹= â€‹48) and normouricemia - reference group (R) (n â€‹= â€‹25). The concentrations of urinary interleukin-18 and KIM-1 were measured using an ELISA kit and were normalized for urinary creatinine (cr.) concentration. RESULTS: The median interleukin-18/cr. Levels in the HU group were significantly higher than in the R group (median, Q1-Q3) 21.83 (11.32-35.96) and 12.68 (7.11-24.04), respectively, (p â€‹< â€‹0.05). The KIM-1/cr. in the HU group and the R group were (median, Q1-Q3) 0.79 (0.45-1.03) and 0.81 (0.59-1.01), respectively, and the difference was not significant. KIM-1/cr. did not differ between the groups. Interleukin-18/cr. ratio correlated positively with serum uric acid concentration (r â€‹= â€‹0.24, p â€‹< â€‹0.05). CONCLUSIONS: Interleukin-18/cr., but not KIM-1/cr. was higher in children with hyperuricemia. Hyperuricemia results in increased IL-18 in urine, in absence of other markers of kidney injury, suggesting inflammation in the kidney. Additional studies on the adults should be done, to confirm this hypothesis.

The Urinary Concentration of Trefoil Factor 3 (TFF3) in the Term and Preterm Neonates.

BACKGROUND: Distinguishing between a pathologic state and renal development is important in neonatology. Because the assessment of serum creatinine in neonates is not reliable, better biomarkers are needed. Trefoil factor 3 (TFF3) is proposed as a biomarker of kidney injury. The study aimed to assess its urinary concentration in healthy term and stable preterm neonates. MATERIAL AND METHODS: The study included 80 term and 20 preterm neonates born in the Department of Perinatology of the University Clinical Hospital in Bialystok. Urine was obtained from the term neonates on the 1st day of life and from the preterm neonates on the 1st, 8th, 15th and 22nd day of life. The urinary concentration of TFF3 was determined using a commercially available immunoassay and was normalized for the urinary creatinine concentration (cr.). RESULTS: The values of TFF3/cr. were higher in the preterm than in the term neonates (p < 0.05) (median (Q1-Q3): 1486.85 (614.92-3559.18) and 317.29 (68.07-671.40) ng/mg cr.). They did not differ in the subsequent days of the preterm neonates' lives. The ROC curve for TFF3/cr. in the preterm and term neonates showed AUC = 0.751 (cut-off value = 1684.25 ng/mg cr.). CONCLUSIONS: Prematurity is associated with higher urinary excretion of TFF3. Male gender is associated with an increased urinary TFF3 excretion in term neonates.

The Urinary Concentrations of Neutrophil Gelatinase-Associated Lipocalin, Cystatin C and Osteopontin in the Healthy Term and Stable Preterm Neonates: A Pilot Study.

BACKGROUND: In neonates, the assessment of kidney function with serum creatinine is limited; therefore, more effective biomarkers are needed. AIM: The study aimed at analyzing the concentrations of renal biomarkers (osteopontin, cystatin C, and NGAL) in neonates. MATERIAL AND METHODS: The study included 80 term and 20 preterm neonates aged 28-33 weeks of gestation. Biomarkers were measured in urine. Term neonates' urine was collected on the 1st day of life. Preterm neonates' urine was collected on the 1st, 8th, 15th, 22nd day of life. Biomarkers' concentrations were normalized to urinary creatinine (cr.) and presented as urinary biomarker/cr. ratios. RESULTS: Median values of biomarker/creatine ratios in term and preterm neonates were the following: cystatin C/cr.: 7.26 and 439.49; osteopontin/cr.: 135.86 and 1633.37; NGAL/cr. in girls: 212.14 and 256.93; and NGAL/cr. in boys 27.123 and 65.29 ng/mg cr. In preterm neonates the cystatin C/cr. ratio was higher on the 1st than on the 8th day. The osteopontin/cr. ratio did not differ between the days. The NGAL/cr. ratio in girls was higher on the 8th than on the 22nd day, and in boys, the lowest was on the 22nd day. CONCLUSIONS: Prematurity in stable, Caucasian neonates might cause higher osteopontin and cystatin C excretion, but not NGAL. The excretion of NGAL and cystatin C, but not osteopontin, may change during first weeks of premature neonate's life.

Urinary Levels of Cathepsin B in Preterm Newborns.

Increased investment in perinatal health in developing countries has improved the survival of preterm newborns, but their significant multiorgan immaturity is associated with short and long-term adverse consequences. Cathepsin B, as a protease with angiogenic properties, may be related to the process of nephrogenesis. A total of 88 neonates (60 premature children, 28 healthy term children) were included in this prospective study. We collected urine samples on the first or second day of life. In order to determine the concentration of cathepsin B in the urine, the commercially available enzyme immunoassay was used. The urinary concentrations of cathepsin B normalized with the urinary concentrations of creatinine (cathepsin B/Cr.) in newborns born at 30-34, 35-36, and 37-41 (the control group) weeks of pregnancy were (median, Q1-Q3) 4.00 (2.82-5.12), 3.07 (1.95-3.90), and 2.51 (2.00-3.48) ng/mg Cr, respectively. Statistically significant differences were found between the group of newborns born at 30-34 weeks of pregnancy and the control group (p < 0.01), and between early and late preterm babies (PTB) (p < 0.05). The group of children born at 35-36 weeks of pregnancy and the control group did not differ significantly. This result suggests that the elevated urinary cathepsin B/Cr. level may be the result of the kidneys' immaturity in preterm newborns.