Abstract: TH-PO0737
Kidney Transcriptomics of Hypertension (HTN) in Minimal Change Disease (MCD) and FSGS
Session Information
- Glomerular Innovations: Artificial Intelligence, Multiomics, and Biomarkers
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Fiseha, Neyat, University of Michigan, Ann Arbor, Michigan, United States
- Hartman, John R., University of Michigan, Ann Arbor, Michigan, United States
- Eddy, Sean, University of Michigan, Ann Arbor, Michigan, United States
- Gonzalez-Vicente, Agustin, Case Western Reserve University, Cleveland, Ohio, United States
- Alakwaa, Fadhl, University of Michigan, Ann Arbor, Michigan, United States
- Sethna, Christine B., Northwell Health, New Hyde Park, New York, United States
Group or Team Name
- NEPTUNE Cardiovascular Working Group.
Background
Individuals with MCD and FSGS are at high risk for HTN; however, molecular markers of HTN in this population are unknown. The objective was to investigate kidney tissue differentially expressed genes (DEG) associated with HTN in MCD/FSGS.
Methods
Participants with MCD or FSGS from the Nephrotic Syndrome Study Network (NEPTUNE) and available RNA sequencing data from glomerular (GLOM) and tubulointerstitial (TI) tissue were used. HTN was defined as either diagnosis of HTN at biopsy, or hypertensive blood pressure on at least three occasions. DEG were examined for association with HTN using unsupervised (genomewide) or supervised (563 targeted genes) models adjusted for age, sex, obesity, FSGS/MCD, eGFR, urine protein/creatinine and antihypertensive medication at a false discover rate of 10%.
Results
Participants included 229 children (age 10 IQR 6-15 yr, 53.7% male) and 386 adults (age 46 IQR 33-58 yr, 60.8% male). HTN was present in 346 (56.2%) participants, with 45.5% on anti-hypertensive medications. Supervised GLOM analysis revealed 82 DGE genes (Figure 1), including upregulation of EMILIN1. Unsupervised analysis yielded no DEG. Supervised GLOM analysis stratified by age yielded 88 genes in adults (Figure 2; including EMILIN1) and none in children. Unsupervised GLOM analysis showed no DEG in either adults or children; nor any of the models in the TI.
Conclusion
Kidney transcriptomics in MCD/FSGS highlighted significant DEGs associated with HTN in GLOM but not in TI tissue. Notably, stratification by age only yielded DEG in adults; underscoring the need for age-specific analyses in future research. EMILIN1, a negative regulator of TGF-β, suggests a possible response in the glomerular vasculature, warranting further research.
Funding
- Other NIH Support