Eicosanoids as Biomarkers of Hyperfiltration-Mediated Injury in CKD
Year: 2026
Type: article
Abstract: Introduction Early biomarkers of hyperfiltration-induced injury are not known. We previously reported elevated urinary Prostaglandin E2 (PGE 2 ) preceding albuminuria in children with solitary kidney, and upregulated Cyclooxygenase-2 (COX2)-PGE 2 -EP2 axis in unilaterally nephrectomized mice. To determine chronic kidney disease (CKD) stage-associated changes in urinary eicosanoids, baseline urine samples from the chronic kidney disease in children (CKiD) biorepository (n=318) and a comparator group of children with enuresis (n=72) were analyzed. Methods Liquid/gas chromatography-mass spectrometry was employed 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 PGE 2 , thromboxane, and DHETs, with a decrease in prostacyclin, F 2 -isoprostane, and 9,10-DIHOME from CKD stage 2 to 3 indicating perturbed metabolism through COX and CYP450 pathways. In unadjusted mixed models quantifying the associations of a two-times higher baseline eicosanoid with initial GFR found prostacyclin, PGE 2 /prostacyclin ratio, thromboxane/prostacyclin ratio, LTE 4 , 9,10-DiHOME, and F 2 -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. Conclusions 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.
Source: Kidney International Reports
Authors: Tarak Srivastava, Ginger L. Milne, Jianping Zhou, Mohammad H. Rezaiekhaligh, Derek K. Ng, Jennifer L. Roem, Bradley A. Warady, Susan L. Furth, Ram Sharma, Mukut Sharma, Kyle Deville, Anjali Nayak, Tom Blydt-Hansen, Cynthia Wong, Isidro Salusky, Elizabeth Ingulli, Robert Mak, Elaine Ku, Cheryl Sanchez-Kazi, Denver Brown, Sonal Bhatnagar, Marissa DeFrietas, Carolyn Abitbol, Larry Greenbaum, Lyndsay Harshman, Priya Verghese, Sonia Krishnan, Marciana Laster, Stefan Kiessling, Margaret Murphy, Aftab Chishti, Siddharth Shah, Samir El-Dahr, Nancy Rodig, Allison Dart, Meredith Atkinson, Cozumel Pruette, Zubin Modi, Jason Thomas, Bradley Warady, Donna Claes, Rebecca Johnson, Eileen Ciccia, Stephen Hooper, Susan Massengill, Liliana Gomez-Mendez, Joann Carlson, Craig Wong, Frederick Kaskel, Jeffrey Saland, Rebecca Levy, Anil Mongia, Mark Mitsnefes, Katherine Dell, Emily Stonebrook, Ikuyo Yamaguchi, Kelsey Richardson, Susan Furth, Erum Hartung, Smitha Vidi, Joshua Samuels, Poyyapakkam Srivaths, Victoria Norwood, Joseph Flynn, Susan Halbach, Victoria Besser, Sharon Bartosh
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,800
Funders: Midwest Veterans' Biomedical Research Foundation, U.S. Department of Veterans Affairs, East Carolina University, Children's Mercy Hospital, Apellis Pharmaceuticals, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development
Awards: Targeting PGE2 Receptors to attenuate shear stress-induced glomerular injury, The Central Biochemistry Laboratory for the Chronic Kidney Disease in Children Cohort (CKiD), The Kidney Disease in Children Data Management and Analysis Center (KIDMAC), Chronic Kidney Disease in Children (CKiD), Chronic Kidney Disease in Children (CKiD V)
OpenAlex ID: W7204250624