Abstract: SA-PO0764
Plasma and Urine Acylcarnitines as Potential Biomarkers for Remission of Proteinuria in FSGS/Minimal Change Disease: Untargeted Metabolomics Study from the NEPTUNE Cohort
Session Information
- Glomerular Diseases: Profiling Through Multiomics
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
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
- Drexler, Yelena, University of Miami, Miami, Florida, United States
- Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
- Mariani, Laura H., University of Michigan, Ann Arbor, Michigan, United States
Background
Remission of proteinuria in focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is closely linked with long-term prognosis. However, the underlying metabolic mechanisms of FSGS/MCD remain poorly understood, making it challenging to predict treatment response. Comprehensive metabolomic profiling offers the potential to identify novel biomarkers associated with treatment outcomes.
Methods
We included 136 participants with FSGS/MCD from the Nephrotic Syndrome Study Network (NEPTUNE). A total of 135 plasma and 135 urine samples were collected at the study baseline visit within 45 days of kidney biopsy. Untargeted metabolomics was performed using liquid chromatography–mass spectrometry (LC-MS). Following rigorous data preprocessing, principal component analysis (PCA) was used to visualize metabolite distributions. Cox-Elastic Net models with 5-fold cross-validation were employed to identify metabolites associated with complete remission of proteinuria (CR; defined as urine protein-to-creatinine ratio <0.3 g/g). Hypergeometric tests were performed to identify enriched metabolite categories among the selected plasma and urine metabolites.
Results
Among the 136 participants, 60.3% had FSGS, 64.0% were adults, and 63.2% were male. Over a median follow-up of 51 months, 50.0% achieved CR. After quality control, 371 plasma and 409 urine metabolites were retained for analysis. PCA plots revealed no distinct separation between FSGS and MCD. Feature selection identified 21 plasma and 24 urine metabolites associated with CR. Hypergeometric tests revealed that fatty esters – specifically acylcarnitines – were the only metabolite category significantly enriched in both plasma and urine in association with CR (Table 1).
Conclusion
Untargeted metabolomic profiling identified acylcarnitines as potential biomarkers for proteinuria remission in FSGS/MCD. Further mechanistic studies focusing on acylcarnitines may provide deeper insights into the disease mechanisms of FSGS/MCD.
Funding
- NIDDK Support