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Abstract: SA-PO962

Kidney Transcriptomics of Blood Pressure (BP) in Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS)

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Sethna, Christine B., Cohen Children's Medical Center, Queens, New York, United States
  • Eddy, Sean, University of Michigan, Ann Arbor, Michigan, United States
  • Alakwaa, Fadhl, University of Michigan, Ann Arbor, Michigan, United States
  • Bitzer, Markus, University of Michigan, Ann Arbor, Michigan, United States
  • Nachman, Patrick H., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Tuttle, Katherine R., University of Washington, Seattle, Washington, United States
  • Hall, Gentzon, Duke University, Durham, North Carolina, United States
  • Srivastava, Tarak, Children's Mercy Kansas City, Kansas City, Missouri, United States
  • Cattran, Daniel C., University of Toronto, Toronto, Ontario, Canada
  • Glenn, Dorey A., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Gonzalez-Vicente, Agustin, Cleveland Clinic, Cleveland, Ohio, United States
  • Hartman, John R., University of Michigan, Ann Arbor, Michigan, United States

Group or Team Name

  • NEPTUNE.
Background

Individuals with MCD and FSGS are at high risk for hypertension and cardiovascular disease, however molecular markers of BP in this population are unknown. The objective was to investigate kidney tissue differential gene expression associated with BP in MCD/FSGS.

Methods

Participants with biopsy-proven MCD or FSGS from the Nephrotic Syndrome Study Network (NEPTUNE) with previously sequenced genome-wide mRNA expression profiling of kidney tissue were included. Glomerular and tubulointerstitial transcriptomics were assessed for differentially expressed (DE) genes in adjusted linear models for enrollment BP. Systolic and diastolic BP were indexed (SBPi/DBPi) to the 95th%ile for children <13 years and to 130 mmHg for those ≥13 years.

Results

Participants included 192 children (age 11 IQR 5-14 yr, 57.3% male) and 370 adults (age 45 IQR 32.8-58.3 yr, 60.8% male), with 28.7% FSGS. Median SBPi was 0.8 IQR 0.70-0.9 and DBPi was 0.87 IQR 0.78-1, with 47.3% on RAAS blockade. Adjusting for sex only, there were 865 genes at 5% and 1622 at 10% FDR associated with SBPi, but none for DBPi. Adjusting for sex, age, and glomerular filtration rate (eGFR) revealed no significant genes for either SBPi or DBPi at 10% FDR (Figure 1). By p-value, the top genes in the SBPi and DBPI models were PNMA8C (p=3.2e-5) and PHTF1 (p=5.6e-5), respectively. There were no DE genes from tubulointerstitial tissue associated with BP.

Conclusion

Though hypertension is an important risk factor for progression of kidney disease, BP was not associated with differential gene expression in kidney tissue after adjusting for common confounders in patients with MCD/FSGS enrolled in NEPTUNE.

Funding

  • NIDDK Support