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Abstract: FR-PO661

Urine Biomarker Analysis of Pediatric Nephrotic Syndrome

Session Information

  • Pediatric Nephrology - II
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology

Authors

  • Cummins, Timothy, University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Merchant, Michael, University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Rane, Madhavi J., University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Mariani, Laura H., University of Michigan Medical School, Ann Arbor, Michigan, United States
  • McCown, Phillip J., University of Michigan Medical School, Ann Arbor, Michigan, United States
  • Ju, Wenjun, University of Michigan Medical School, Ann Arbor, Michigan, United States
  • Wilkey, Daniel Wade, University of Louisville School of Medicine, Louisville, Kentucky, United States
  • Pathmasiri, Wimal, University of North Carolina at Chapel Hill Nutrition Research Institute, Kannapolis, North Carolina, United States
  • Mcritchie, Susan, University of North Carolina at Chapel Hill Nutrition Research Institute, Kannapolis, North Carolina, United States
  • Dougherty, Julie, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Jortani, Saeed A., University of Louisville, Louisville, Kentucky, United States
  • Kretzler, Matthias, University of Michigan Medical School, Ann Arbor, Michigan, United States
  • Sumner, Susan Jenkins, University of North Carolina at Chapel Hill Nutrition Research Institute, Kannapolis, North Carolina, United States
  • Smoyer, William E., Nationwide Children's Hospital, Columbus, Ohio, United States
  • Klein, Jon B., University of Louisville School of Medicine, Louisville, Kentucky, United States
Background

The molecular underpinnings of pediatric nephrotic syndrome remain unclear. Response to immunosuppressive therapy is relatively poor in many patients with Focal Segmental Glomerular Sclerosis (FSGS) as compared to children with Minimal Change Disease (MCD). Elucidation of glomerular disease biomarkers that predict treatment response would be critical towards improved outcomes in pediatric nephrotic syndrome. Identification of subpopulations of nephrotic syndrome by proteomics could indicate differences in patient outcomes. We addressed the hypothesis that comparison of urine proteomes in children with MCD and FSGS could distinguish disease activity and molecular mechanisms of disease progression.

Methods

Proteomic analysis was conducted on urine from children with MCD and FSGS enrolled in the CureGN Consortium to determine differences in disease activity. Urine specimens from 216 patients were analyzed by 2D-LC-MS/MS. MetaboAnalyst 5.0 was employed to perform statistical analyses to identify candidate urine biomarkers of disease activity in pediatric FSGS and MCD. Confirmation ELISA assays were performed for ORM1 and C3. K-means clustering was conducted on nephrotic urine proteome to identify patient clusters.

Results

Proteomic profiles in complete remission urine were dramatically different from nephrotic specimens. ORM1 and C3 levels are significantly higher in nephrotic urine vs complete remission. Unsupervised clustering of nephrotic proteomes showed two distinct clusters suggesting subgroups of patients.

Conclusion

Our findings indicate the potential for ORM1 and C3 to be biomarkers of disease activity. Unsupervised clustering analysis of nephrotic urine proteome indicated a cluster with increased immune response and complement proteins.

Funding

  • NIDDK Support