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Abstract: FR-PO723

Urinary Lipid Biomarkers Predict Progression in Focal Segmental Glomerulosclerosis

Session Information

  • Pediatric Nephrology - 1
    October 25, 2024 | Location: Exhibit Hall, Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology

Authors

  • Humphrey, Jacob A., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Armando, Aaron M., University of California San Diego, La Jolla, California, United States
  • Quehenberger, Oswald, University of California San Diego, La Jolla, California, United States
  • Troost, Jonathan P., University of Michigan, Ann Arbor, Michigan, United States
  • Erkan, Elif, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Background

Focal Segmental Glomerulosclerosis (FSGS) is the most common glomerular cause of pediatric end stage kidney disease. We propose that patients with FSGS display a unique milieu of urinary and serum free fatty acid (FFA) and phospholipid (PL) profiles that can serve as biomarkers for prediction of diagnosis and prognosis in FSGS.

Methods

Urine and serum samples were obtained from 30 patients with FSGS and MCD as an ancillary study to Nephrotic Syndrome Study Network (NEPTUNE) cohort. Healthy controls were obtained from Discovery biobank, Cincinnati Children’s Hospital. We included patients aged 2-21 years with biopsy proven FSGS or MCD, urine protein to creatinine ratio (UPCR) of >1 and eGFR >60mL/min/1.73m2 . We excluded patients with DM, systemic disease, organ/bone marrow transplantation, or known genetic cause of FSGS. Targeted lipidomic analysis was performed by mass spectrometry to measure PL and FFA in samples. Disease progression was defined as a 20% decrease in eGFR. Logistic regression models with unadjusted/adjusted models for age, race and proteinuria were utilized to determine ROC curves and AUC.

Results

Mean follow up was 48 months (IQR 30-56 months). Serum arachidic acid (p = 0.02) and very long chain fatty acid (VLCFA) cerotic acid (p = 0.02) were elevated in FSGS patients. Urinary omega-3 FA, eicosapentaenoic acid (AUC 0.86, p = 0.0007) and omega-6 FA, arachidonic acid (AA) (AUC 0.76, p=0.002) and AA by products polyunsaturated adrenic acid (AUC 0.9, p = 0.01), docosapentaenoic acid ( n3 and n6, AUC 0.93 and 0.84, p = 0.003 and 0.01, respectively) and PL metabolite lysophosphatidylcholine (LPC)(AUC 0.8, p = 0.004) predicted FSGS progression by univariate analysis in adjusted and unadjusted models.

Conclusion

Lipidomic analysis of serum and urine samples provided key information in pathophysiology of FSGS and identified potential biomarkers. Elevated serum levels of VLCFA in patients with FSGS suggest peroxisomal dysfunction and defective fatty acid β oxidation. Elevated urine AA and its metabolites in association with membrane PL and LPC serve as potential biomarkers for progression in FSGS. We postulate that increased activity of proinflammatory AA and LPC driven by phospholipase A2 contributes to progression in FSGS.

Funding

  • Other NIH Support