Kidney Week

Abstract: TH-PO447

Metabolomics Provides Insights Into Remission of Pediatric Nephrotic Syndrome During Treatment

Session Information

• Glomerular Diseases: Podocytopathies and Nephrotic Syndromes
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1302 Glomerular Diseases: Immunology and Inflammation

Authors

• Mcritchie, Susan, The University of North Carolina at Chapel Hill Nutrition Research Institute, Kannapolis, North Carolina, United States

Susan Mcritchie,

• Pathmasiri, Wimal, The University of North Carolina at Chapel Hill Nutrition Research Institute, Kannapolis, North Carolina, United States

Wimal Pathmasiri,

• Mariani, Laura H., University of Michigan, Ann Arbor, Michigan, United States

Laura H. Mariani,

• Cummins, Timothy, University of Louisville School of Medicine, Louisville, Kentucky, United States

Timothy Cummins,

• Merchant, Michael, University of Louisville School of Medicine, Louisville, Kentucky, United States

Michael Merchant,

• Jortani, Saeed A., University of Louisville, Louisville, Kentucky, United States

Saeed A. Jortani,

• Dougherty, Julie, Nationwide Children's Hospital, Columbus, Ohio, United States

Julie Dougherty,

• Kamigaki, Yu, Nationwide Children's Hospital, Columbus, Ohio, United States

Yu Kamigaki,

• Klein, Jon B., University of Louisville School of Medicine, Louisville, Kentucky, United States

Jon B. Klein,

• Smoyer, William E., Nationwide Children's Hospital, Columbus, Ohio, United States

William E. Smoyer,

• Sumner, Susan Jenkins, The University of North Carolina at Chapel Hill Nutrition Research Institute, Kannapolis, North Carolina, United States

Susan Jenkins Sumner,

Background

Children diagnosed with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) vary in response to therapy and risk of relapse. Those with persistent proteinuria and/or frequent relapses have the highest risk of disease progression, but little is known about the mechanism of kidney damage in these forms of nephrotic syndrome. Metabolomics studies the changes in downstream metabolites in biological pathways and enables capturing perturbations in metabolic pathways that can provide insights into mechanisms underlying disease pathophysiology and response to treatment. Developing non-invasive biomarkers to predict and/or define mechanisms of response to treatment is an urgent need for glomerular disease. Thus, we sought to identify perturbed biological pathways in pediatric patients with MCD or FSGS to understand the underlying mechanisms in nephrotic proteinuria (NP; UPCR>3.5) vs. complete remission (CR; UPCR<0.3).

Methods

Urine specimens obtained from pediatric patients enrolled in the prospective CureGN Study with biopsy-confirmed MCD or FSGS were analyzed with ¹H NMR metabolomics. 147 urine samples from those in CR or with NP were used as a discovery set. A second cohort of 112 similarly categorized samples acted as a replication set. Binned NMR data were analyzed using multivariate analyses, hypothesis testing, and logistic regression. NMR bins were library-matched to metabolites and those that were important to differentiating CR and NP in both data sets were used for pathway enrichment analyses.

Results

Metabolomics analysis could clearly differentiate CR from NP in patients with MCD or FSGS. Aminoacyl t-RNA biosynthesis, pathways related to immune responses, and amino acid metabolism were among the top enriched pathways in the remission state compared to those with NP.

Conclusion

Metabolomics can clearly differentiate pediatric patients with biopsy-confirmed MCD and/or FSGS with nephrotic proteinuria vs. complete remission. Metabolic perturbations in the identified pathways warrant further investigation using targeted metabolomics to develop non-invasive predictive biomarkers towards identifying potential novel therapeutic targets in patients with nephrotic syndrome.

Funding

• NIDDK Support