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Abstract: FR-PO410

Urine Eicosanoids as Markers of Hyperfiltration-Mediated Injury in the Chronic Kidney Disease in Children (CKiD) Study

Session Information

  • Pediatric Nephrology - I
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1800 Pediatric Nephrology

Authors

  • Srivastava, Tarak, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, United States
  • Staggs, Vincent S., Children's Mercy Hospitals and Clinics, Kansas City, Missouri, United States
  • Milne, Ginger, Vanderbilt University, Nashville, Tennessee, United States
  • Warady, Bradley A., Children's Mercy Hospitals and Clinics, Kansas City, Missouri, United States
  • Furth, Susan L., The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Sharma, Mukut, Kansas City VA Medical Center, Kansas City, Missouri, United States
Background

Our work on hyperfiltration-mediated injury in animal models identified upregulated cyclooxygenase-2-Prostaglandin E2 (PGE2)-Prostanoid receptor EP2 pathway. We found increased urine PGE2/Creatinine levels in children with a solitary kidney. Our long-term goal is to identify urinary biomarkers for hyperfiltration-mediated injury. Presently, we compared urinary eicosanoid metabolite levels between controls and children with CKD Stage 2, 3a and 3b in the CKiD cohort.

Methods

Urine samples from 318 CKiD children with glomerular (Glom; n=92) and non-glomerular (N-Glom; n=226) CKD. Enuretic children (n=72) served as controls. Urine PGE2, PGD2, Prostacyclin (PGI2), leukotriene E4 (LTE4), Thromboxane (Txb2), 9,10-Dihydroxy-12-octadecenoic acid (9,10-DiHOME), 12,13-dihydroxy-9-octadecenoic acid (12,13-DiHOME), 8,9-dihydroxyicosatrienoic acid (8,9-DHET), 11,12-DHET, and 14,15-DHET were measured by liquid chromatography-tandem mass spectrometry. Brunner-Munzel test and Spearman correlation were used for statistical analysis.

Results

Urine PGE2, PGD2, LTE4, TxB2, 8,9-DHET, 11,12-DHET, 14,15-DHET and 12,13-DiHOME were significantly increased in CKD; PGI2 and 9,10-DiHOME were significantly decreased (Tables). These metabolites changed incrementally from CKD Stage 2 to 3a to 3b (data not shown). TxB2, 12,13-DiHOME, 11,12-DHET and 14,15-DHET were significantly higher in N-Glom vs. Glom. eGFR correlated significantly with PGE2 (p<0.001), PGI2 (p<0.001), and 9,10-DiHOME (p<0.001).

Conclusion

Urine PGE2, PGI2, and 9,10-DiHOME are good biomarkers for hyperfiltration-mediated injury as they incrementally change with CKD stages, are comparable in Glom and N-Glom disease, and correlate with eGFR.

Funding

  • NIDDK Support