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Abstract: FR-PO662

Multi-Omic Serum Profiling in Children and Young Adults Affected by Steroid-Dependent 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

  • Bruschi, Maurizio, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Garbarino, Andrea, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Kajana, Xhuliana, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Spinelli, Sonia, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Angeletti, Andrea, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Lugani, Francesca, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Caridi, Gianluca, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • La Porta, Edoardo, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Verrina, Enrico E., Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Ghiggeri, Gian Marco, Istituto Giannina Gaslini, Genova, Liguria, Italy
Background

Idiopathic nephrotic syndrome (INS) is the most common cause of proteinuria in children and young adults. The mainstay of therapy is steroids and based on treatment response, patients can be classified as dependent or resistant. However, there are no validated biomarkers able to predict treatment response or even to identify the biochemical pathways involved in the pathogenesis of INS.

Methods

We performed a proteomic and lipidomic analysis on serum samples of 82 children and young adults with steroid-dependent INS enrolled in a randomized clinical trial (NCT02394119). With the aim to limit confounding factors due to protein and lipid dysregulation that characterized the acute phases of INS, serum samples were collected during remission. Therefore, all patients had no proteinuria. As control group, we used 26 healthy donors matched for age and sex.

Results

Multi-omics analysis identified a total of 307 and 3.027 unique gene proteins and lipids respectively. Statistical analysis revealed the upregulation of 8 proteins and 38 lipids and the downregulation of 20 proteins and 18 lipids. Moreover, by combining multiple algorithms, including machine learning analysis, we identified a core panel of features able to clearly distinguish between INS patients and healthy donors. In addition, functional analysis of these panel of features revealed the main biological processes associated to steroid-dependent INS patients.

Conclusion

This study confirmed that the multi-omics approach allows to identify a core panel of biomarkers specific for steroid-dependent INS. As a strength point, we emphasize that INS patients had no proteinuria. Therefore, our findings may suggest that INS is characterized by several protein and lipid fingerprints not related to the remission or recurrence phases. Our results may represent the base for further investigation into the still unknown pathogenetic mechanisms of INS.

Funding

  • Government Support – Non-U.S.