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Abstract: TH-PO983

Association Between Kidney Tissue Estrogen Gene Signature and Nephrotic Syndrome Remission

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Bellomo, Tiffany Rose, University of Michigan, Ann Arbor, Michigan, United States
  • Hartman, John R., University of Michigan, Ann Arbor, Michigan, United States
  • Hladunewich, Michelle A., University of Toronto, Toronto, Ontario, Canada
  • O'Shaughnessy, Michelle M., Stanford University, Palo Alto, California, United States
  • Oliverio, Andrea L., University of Michigan, Ann Arbor, Michigan, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
  • Larkina, Maria, University of Michigan, Ann Arbor, Michigan, United States
  • Mariani, Laura H., University of Michigan, Ann Arbor, Michigan, United States
Background

Kidney disease severity and rate of progression are reported to be higher in males than females, which may in part be mediated by glomerular sex hormone receptor expression. We developed a kidney tissue estrogen gene signature to examine associations between estrogen signaling and remission from nephrotic syndrome.

Methods

Patients with active FSGS, MCD, MN, or other nephrotic syndrome at enrollment in NEPTUNE, a multi-center observational cohort study were studied. Our outcome of interest was complete remission, defined as a uPCR ≤0.3 g/g. Our exposure of interest was a novel estrogen z-score. First, genes affected by estrogen signaling were defined as any gene related to ESR1 and 2 in both the HumanBase (Flatiron Institute) and MSigDB (Broad Institute) databases. Genes were limited to only those with estrogen response elements in the promoter region and 21 genes of interest were identified. Genome wide RNA expression data from the glomerular compartment of kidney tissue were used to calculate a z-score (X-mean/SD) for each gene. Each patient’s overall z-score was generated from the average of the individual gene z-scores.

Results

Among the 177 patients, 67% were male, mean age was 34 years, mean eGFR was 86 ml/min/1.73m2, and mean uPCR was 2.8 g/g. A cox proportional hazards model controlling for age, sex, eGFR, and uPCR demonstrated a significant association between overall Z score and time to complete remission (HR 4.59; 95% Cl 1.4-15.1; p=0.012). Figure 1 shows unadjusted association of z-score median split with time to remission.

Conclusion

Higher estrogen score was associated with a higher hazard for complete remission. This estrogen gene signature could be used in both research and clinical practice to more carefully risk stratify patients. These findings also identify the estrogen receptor as a potential therapeutic target in glomerular disease.

Funding

  • NIDDK Support