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Abstract: TH-PO530

Clinical and Molecular Correlates of Quantitative Foot Process Effacement Assessment in the NEPTUNE Cohort

Session Information

  • Pathology and Lab Medicine
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

  • 1700 Pathology and Lab Medicine

Authors

  • Delsante, Marco, Universita degli Studi di Parma, Parma, Emilia-Romagna, Italy
  • Rossi, Giovanni Maria, Universita degli Studi di Parma, Parma, Emilia-Romagna, Italy
  • Fenaroli, Paride, Universita degli Studi di Parma, Parma, Emilia-Romagna, Italy
  • Benigno, Giuseppe Daniele, Universita degli Studi di Parma, Parma, Emilia-Romagna, Italy
  • Peyronel, Francesco, Meyer Children's Hospital, Florence, Italy
  • Cocchi, Enrico, Columbia University Irving Medical Center, New York, New York, United States
  • Troost, Jonathan P., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Eddy, Sean, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Barisoni, Laura, Duke Medicine, Durham, North Carolina, United States
  • Kretzler, Matthias, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Zee, Jarcy, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Maggiore, Umberto, Universita degli Studi di Parma, Parma, Emilia-Romagna, Italy
  • Rosenberg, Avi Z., Johns Hopkins Medicine, Baltimore, Maryland, United States
Background

Foot process effacement (FPE) is the ultrastructural hallmark of podocytopathies and is traditionally a visual estimate of percentage foot process loss (%FP). Foot process width (FP-W) could be a more accurate measure of FPE, but whether FP-W robustly correlates with clinical outcomes or gene expression is unknown

Methods

%FP was extracted from NEPTUNE study core data. FP-W was measured on micrographs >4000x in minimal change disease (MCD) or FSGS NEPTUNE participants. FPE relationship with laboratory markers of nephrotic syndrome (NS) and CKD was examined. We used weighted gene coexpression network analysis (WGCNA) of gene expression biopsy data to identify Gene Modules (GM) that correlated with FPE and tested a subset of single genes (Sub-GSE) known to be differentially expressed in podocytopathies

Results

55 MCD and 36 FSGS patients had longitudinal follow-up, 42 had gene expression data. %FP were similar between the two groups, FP-W was slightly higher in FSGS versus MCD. %FP and FP-W were associated with longitudinal changes in clinical parameters of NS. Larger FPE extent on biopsy showed greater improvement of serum albumin, cholesterol, and UPCR during follow up (P<0.05); this correlation was attenuated when corrected for %FP. WGCNA (Fig. 1) and Sub-GSE showed that FPE is associated with increased expression of GM, including complement-related genes

Conclusion

FPE extent is associated with NS improvement, likely reflecting sensitivity to therapies. FP-W does not add prognostic information beyond %FP. FPE is associated with several genes expression (i.e, complement factors)

Eigengene network (Gene Modules and the FP-W)