103 - Urine eicosanoids as biomarkers in children with solitary kidney (SK)
Friday, April 22, 2022
6:15 PM – 8:45 PM US MT
Poster Number: 103 Publication Number: 103.138
Tarak Srivastava, Children's Mercy Hospital, Kansas City, MO, United States; Vincent Staggs, Children's Mercy KC / University of Missouri-Kansas City, Kansas City, MO, United States; Ginger L. Milne, Vanderbilt University School of Medicine, Nashville, TN, United States; Mukut Sharma, Kansas City VA Medical Center, Kansas City, MO, United States
Attending Nephrologist Children's Mercy Hospital Children's Mercy Hospitals and Clinics Kansas City, Missouri, United States
Background: An estimated 20%-40% of children born with a SK develop ESRD by young adulthood which is attributed to persistent hyperfiltration-mediated injury that starts early in life. Biomarkers of hyperfiltration are not known. The glomerular hemodynamic changes in SK are a result of changes in vasoactive metabolites. Arachidonic acid derived lipid mediators including Prostaglandin E2 (PGE2) are potent vascular modulators. Our previous work into on hyperfiltration-mediated injury in animal models of unilateral nephrectomy led us to identification of the cyclooxygenase-2 (COX2)-PGE2-Prostanoid receptor EP2 pathway (Am J Physiol 2014; F1323).
Objective: Our long-term goal is to identify a urinary biomarker of hyperfiltration-mediated injury in children born with SK based on our previous in vitro and in vivo studies. Presently, we compared urinary eicosanoids levels between healthy and SK children.
Design/Methods: Children cared for SK and healthy children seen for enuresis were included in the study. Age, gender, height, weight, and blood pressure (BP) data and scavenged urine sample were collected at the clinic visit. Z-scores were calculated for height, weight, body mass index (BMI) and BP for age and gender across the two groups. Urine PGE2, PGD2, Prostacyclin, leukotriene E4 (LTE4), Thromboxane, 8,9-dihydroxyicosatrienoic acid (8,9-DHET), 11,12-DHET, 14,15-DHET, 9,10-Dihydroxy-12-octadecenoic acid (9,10-DiHOME), 12,13-dihydroxy-9-octadecenoic acid (12,13-DiHOME) and F2-Isoprostane were measured by liquid chromatography-tandem mass spectrometry at the Eicosanoid Core Laboratory, Nashville TN. The data is presented as median with interquartile range. Generalized Wilcoxon tests were used for unadjusted differences between the two groups.
Results: There were 72 healthy (49 boys) and 57 children with SK (37 boys). There was no statistically significant difference in age, Z-scores for height, weight, and systolic BP between the two groups. Children with SK were lighter and had higher diastolic BP. eGFR, as expected, was lower in children with SK compared to control (p=0.067). Urine PGE2, Thromboxane, 11,12-DHET, and 14,15-DHET were elevated in children with SK. There was no statistically significant difference in the two groups for other eicosanoids (Table 1). There was significant negative correlation with age, but not with Z-scores for height, weight, and BMI for urine PGE2, Thromboxane and 11,12-DHET. Thromboxane was positively correlated with Z-scores for SBP and DBP (Table 2).Conclusion(s): Urine PGE2, Thromboxane, 11,12-DHET, and 14,15-DHET are potential biomarkers for hyperfiltration-mediated injury in SK. Table 1Median values and interquartile range (parantheses) for the demographic data and the measured urinary eicosanoids in control and children with SK are shown. Generalized Wilcoxon test was used to compare the two groups. Table 2The correlation between PGE2, Thromboxane, 11,12-DHET or 14,15-DHET with the demographic data is shown. Spearman’s correlation analysis was used.