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Abstract: FR-OR60

A Multi-Omics Approach to IgA Nephropathy Characterization in the NURTuRE Cohort Enables Precision-Based Treatment Approaches

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

  • Olson, N. Eric, Chinook Therapeutics Inc, Seattle, Washington, United States
  • Cox, Jennifer H., Chinook Therapeutics Inc, Seattle, Washington, United States
  • Lo, I-Ju, Evotec International GmbH, Gottingen, Niedersachsen, Germany
  • Ragan, Seamus, Chinook Therapeutics Inc, Seattle, Washington, United States
  • Michel, Niklas, Evotec International GmbH, Gottingen, Niedersachsen, Germany
  • Pospiech, Johannes, Evotec International GmbH, Gottingen, Niedersachsen, Germany
  • Bayerlová, Michaela, Evotec International GmbH, Gottingen, Niedersachsen, Germany
  • Romoli, Simone, Chinook Therapeutics Inc, Seattle, Washington, United States
  • Sathaliya, Taher, Chinook Therapeutics Inc, Seattle, Washington, United States
  • Bohnenpoll, Tobias, Evotec International GmbH, Gottingen, Niedersachsen, Germany
  • Stroth, Nikolas, Evotec International GmbH, Gottingen, Niedersachsen, Germany
  • Radresa, Olivier, Evotec International GmbH, Gottingen, Niedersachsen, Germany
  • King, Andrew J., Chinook Therapeutics Inc, Seattle, Washington, United States
  • Andag, Uwe, Evotec International GmbH, Gottingen, Niedersachsen, Germany
Background

IgA nephropathy (IgAN) is the most commonly reported primary glomerulonephritis, yet risk stratification and prediction of treatment response remain a challenge. Systems biology approaches integrating multiple data types have the potential to identify patient subsets that could benefit from precise treatment approaches. Here we describe a multi-omics analysis of the NURTuRE IgAN patient cohort to generate an integrated understanding of disease pathogenesis and patient stratification.

Methods

Data collected from 205 patients with IgAN in the NURTuRE cohort included clinical characteristics, MEST-C scores for glomerular and tubular injury, serum proteomics using the Olink Explore panel of 3072 analytes and blood and kidney transcriptomes (Table). Relationships between serum proteins, kidney function, kidney and blood gene expression and histopathology were determined using Spearman correlation, ANOVA and Kruskal-Wallis tests.

Results

Serum protein levels of TNFSRF1A, B2M, LCN2, APRIL and TNFRSF17 were inversely correlated with eGFR. Analysis by MEST-C score identified proteins significantly associated with the tubular atrophy/interstitial fibrosis (T) score, including LCN2 and B2M, which are increased in patients with T1 or T2. Analysis of kidney biopsy gene expression by MEST-C score showed that scores for an inflammatory response gene signature were significantly higher in kidney biopsies from patients with T1 or T2.

Conclusion

A multi-omics approach to the characterization of IgAN in the NURTuRE cohort was performed, integrating clinical, histological, transcriptomic and serum proteomic data to gain deeper insights into patient stratification and disease biology. These learnings will be applied to clinical studies evaluating atrasentan, an endothelin receptor A antagonist, and BION-1301, an anti-APRIL antibody, for the treatment of IgAN.

Percent of Patients

Funding

  • Commercial Support