Abstract: TH-OR22
Plasma Metabolic Profiles and Clinical Outcomes in Focal Segmental Sclerosis (FSGS) and Minimal Change Disease (MCD)
Session Information
- Glomerular Diseases: Clinical and Translational Studies
November 02, 2023 | Location: Room 103, Pennsylvania Convention Center
Abstract Time: 04:39 PM - 04:48 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Ozeki, Takaya, University of Michigan, Ann Arbor, Michigan, 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
Background
Metabolomics is a powerful approach to investigate the relationship between disease mechanisms and patients’ phenotype. However, the association between plasma metabolic profiles and clinical outcomes of focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) has not been studied well.
Methods
Plasma samples from 135 FSGS/MCD participants in the Nephrotic Syndrome Study Network (NEPTUNE) were studied. Samples were collected within 45 days from kidney biopsy. Untargeted metabolomics data were obtained using liquid chromatography mass spectrometry (LC-MS). We performed rigorous preprocessing to identify metabolites, remove outliers, and impute missing values. Outcomes with our interest were time to complete remission of proteinuria (UPCR<0.3) and, time to composite renal outcome (40% decline of eGFR or ESKD). Metabolites associated with clinical outcomes were selected by Cox-Elastic Net algorithm. Among the selected metabolites, a hypergeometric test was performed to identify the enriched metabolite categories.
Results
Among the 135 participants, 85 (63.0%) were male, 49 (36.3%) were pediatrics and 81 (60.0%) were FSGS. Median UPCR level was 1.65, and 42 (31.1%) demonstrated nephrotic range proteinuria (UPCR>3.5). Median eGFR levels was 84.2 at the time of sample collection. During the follow-up period (median: 51 months), 47 attained complete remission and 33 reached to composite renal outcome. From the metabolomics data, 371 high-quality named metabolites were analyzed. Cox-Elastic Net models selected 21 and 47 endogenous metabolites that associated with time to complete remission and eGFR decline or ESKD, respectively. Among 87 metabolite categories, hypergeometric tests revealed that Fatty esters and were associated with complete remission while Bile acids were associated with eGFR decline or ESKD.
Conclusion
Specific combinations of plasma metabolites, particularly included as lipids and lipid derivatives, were associated with clinical outcomes in FSGS/MCD, which could help to understand disease mechanisms and can be potential biomarkers to improve treatment strategies.
Funding
- NIDDK Support