Document Type

Article

Publication Date

11-2026

Identifier

DOI: 10.1016/j.ekir.2026.107052; PMCID: PMC13672976

Abstract

INTRODUCTION: Early biomarkers of hyperfiltration-induced injury are not known. We previously reported elevated urinary prostaglandin E2 (PGE2) preceding albuminuria in children with solitary kidney, and upregulated cyclooxygenase-2 (COX2)-PGE2-EP2 axis in unilaterally nephrectomized mice. To determine chronic kidney disease (CKD) stage-associated changes in urinary eicosanoids, baseline urine samples from the CKD in children (CKiD) biorepository (n = 318) and a comparator group of children with enuresis (n = 72) were analyzed.

METHODS: Liquid or gas chromatography-mass spectrometry was used to measure metabolites of arachidonic acid and linoleic acid (ng/mg creatinine, P ≤ 0.05).

RESULTS: The CKiD cohort included children with congenital anomalies of the kidney and urinary tract (CAKUT) (71%, n = 226) and glomerular disease (29%, n = 92). Glomerular filtration rate (GFR) measurement (Iohexol) showed 27% and 73% of CAKUT subjects at CKD stages 2 and 3, respectively. Among those with glomerular disease, 42% and 58% were at CKD stages 2 and 3, respectively. Comparisons across CKD stages identified increase in urinary PGE2, thromboxane, and dihydroxy eicosatrienoic acids (DHETs), with a decrease in prostacyclin, F2-isoprostane, and 9,10-dihydroxy-octadecenoic acids (DiHOMEs) from CKD stage 2 to 3 indicating perturbed metabolism through COX and cytochrome P-450 (CYP450) pathways. In unadjusted mixed models quantifying the associations of a 2-times higher baseline eicosanoid with initial GFR found prostacyclin, PGE2/prostacyclin ratio, thromboxane/prostacyclin ratio, LTE4, 9,10-DiHOME, and F2-Isoprostane were significantly associated with higher initial GFR and remained significant after adjusting for CAKUT diagnosis, sex and baseline age, proteinuria, and hypertension. However, none of the eicosanoids were associated with change in GFR over time or time to kidney replacement therapy.

CONCLUSION: We report for the first time linoleic acid-derived metabolites in children with CKD. A longitudinal study is needed to validate selected urinary eicosanoids as early biomarkers of hyperfiltration.

Journal Title

Kidney Int Rep

Volume

11

Issue

11

First Page

107052

Last Page

107052

PubMed ID

42891043

Keywords

CAKUT; CKD stages 2 and 3; dihydroxy-octadecenoic acids (DiHOMEs); eicosanoids; glomerular disease; hyperfiltration

Comments

Grants and funding

This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.

Publisher's Link: https://www.kireports.org/article/S2468-0249(26)03284-5/fulltext

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