Kidney Week

Abstract: TH-PO545

Glomerular Transcriptomics Reveal Clinically Relevant Endothelial Disturbances in Idiopathic Nephrotic Syndrome

Session Information

• Glomerular Diseases: Omics, Biomarkers, and Tools
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Nelson-Taylor, Sarah K., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Sarah K. Nelson-Taylor, MD, PhD

• Giannini, Courtney, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Courtney Giannini, MD, PhD

• Troost, Jonathan P., University of Michigan, Ann Arbor, Michigan, United States

Jonathan P. Troost, PhD

• Srivastava, Tarak, Children's Mercy Kansas City, Kansas City, Missouri, United States

Tarak Srivastava, MD, FASN

• Zee, Jarcy, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Jarcy Zee, PhD

• Bitzer, Markus, University of Michigan, Ann Arbor, Michigan, United States

Markus Bitzer, MD

• Barisoni, Laura, Duke University, Durham, North Carolina, United States

Laura Barisoni, MD

• Johnson, Richard J., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Richard J. Johnson, MD

• Cara-Fuentes, Gabriel M., Nationwide Children's Hospital, Columbus, Ohio, United States

Gabriel M. Cara-Fuentes, MD, PhD

Background

There is a growing evidence that the glomerular endothelium is important in podocytopathies presenting as idiopathic nephrotic syndrome (INS). In this study we characterize the expression 10 selected genes associated with glomerular endothelial health and injury in patients with INS.

Methods

N=53 healthy controls and N=153 INS NEPTUNE participants with biopsy proven minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) and mRNA expression profiling from micro-dissected human glomeruli were included. Gene expression was analyzed according to the histological diagnosis (MCD vs. FSGS) and disease state (relapse/remission). Correlation between gene expression, clinical features (proteinuria, kidney function -eGFR) and validated ultrastructural endothelial (loss of fenestrations, etc.) and podocyte descriptors (foot process effacement, etc.) was performed. Statistical analyses included two-way ANOVA and Pearson correlation.

Results

Endothelial-specific genes related to endothelial health and barrier integrity (NOS3, ESAM, ESM1), glycocalyx injury (HPSE, HYAL1, MMP2, MMP9, ADAMTS1) and cell activation (ICAM1, CAV1) were significantly altered in INS patients (Fig. 1 shows representative results) compared to controls, independent of the histological pattern and disease state. High ICAM1, CAV1 and HPSE expression associated with low eGFR. NOS3 and CAV1 associated with loss of endothelial cell fenestrations, and MMP2 with loss endothelial cell honeycombing appearance. Analysis of gene expression and podocyte descriptors is in process.

Conclusion

Glomerular expression of genes associated with endothelial health is altered in INS, regardless of histological patterns or disease state, and associates with low eGFR and endothelial ultrastructural injury.

Funding

• Private Foundation Support