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Abstract: TH-PO625

Lipidomics Analysis Reveals Biomarkers for Proteinuria Remission and Disease Progression in FSGS/Minimal Change Disease (MCD) from the NEPTUNE Cohort

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Ozeki, Takaya, University of Michigan, Ann Arbor, United States
  • Alakwaa, Fadhl, University of Michigan, Ann Arbor, Michigan, United States
  • Mathew, Anna Vachaparampil, University of Michigan, Ann Arbor, Michigan, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
  • Mariani, Laura H., University of Michigan, Ann Arbor, Michigan, United States

Group or Team Name

  • NEPTUNE (Nephrotic Syndrome Study Network).
Background

FSGS/MCD exhibits significant heterogeneity, presenting a challenge for effective treatment. Assessment of the systemic metabolic changes reflected in circulating lipids and capture of lipid signaling molecules can illuminate this complexity.

Methods

We examined 131 participants with FSGS/MCD from the NEPTUNE cohort, analyzing plasma samples collected within 45 days of kidney biopsy. Lipidomics profiles were obtained through liquid chromatography-mass spectrometry (LC-MS), utilizing in silico tandem mass spectral databases for identification and established normalization method. Rigorous data filtration included the removal of low variance and high missing rate features, missing value imputation, log transformation, and scaling. A Cox-Elastic Net model with 5-fold cross-validation was employed to identify lipids associated with complete remission of proteinuria (CR, UPCR<0.3) and disease progression (40% decline of eGFR or ESKD).

Results

Among the 131 participants, 59.5% had FSGS, 64.1% were adults, and 62.6% were male. Median UPCR level was 1.65, and 31.3% had nephrotic range proteinuria (UPCR>3.5). Median eGFR levels was 84.1 at the sample collection. Over a median follow-up of 51.0 months, 50.0% achieved CR, while 26.2% reached to the composite renal outcomes. We measured 984 plasma lipids, of which 732 met our stringent quality criteria for further analysis. Among these, 37 lipids were associated with CR and 69 with disease progression. Notably, five of them were linked to both outcomes and belong to the Glycerophospholipids, Sphingolipids, and Glycerolipids lipid categories (Table 1).

Conclusion

This lipidomics analysis of FSGS/MCD patients identified specific lipid classes, including Glycerophospholipids, Sphingolipids, and Glycerolipids, as potential biomarkers for proteinuria remission and disease progression. These findings can offer insights into the heterogeneity in FSGS/MCD and suggest avenues for personalized therapeutic interventions. Further mechanistic studies are needed to elucidate the specific roles of these lipid categories in remission of proteinuria and disease progression.

Funding

  • NIDDK Support