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Abstract: FR-PO602

Integration of Exostosin 1 and 2 Into a Clinical Care Pathway for Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation

Authors

  • Brown, Jennifer A., University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
  • Chung, Hyunjae, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
  • Andonegui, Graciela, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
  • Benediktsson, Hallgrimur, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
  • Muruve, Daniel A., University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
  • Chun, Justin, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
Background

Membranous lupus nephritis (MLN), is a renal manifestation of systemic lupus erythematous. The identification of biomarkers presents an avenue to better explain the pathogenesis, diagnosis, and prognosis of many heterogenous glomerulonephritides. Exostosin 1 and 2 (EXT1 and 2) are proteins that have recently been found in secondary membranous nephropathies including MLN. Exisiting literature suggests that EXT-associated membranous nephropathy represents a distinct clinical phenotype, with EXT-negative disease leading to higher risk of renal failure, but exactly how these groups differ has not yet been well described.

Methods

We evaluated a cohort of 28 patients reported as isolated MLN from the Biobank for the Molecular Classification of Kidney Disease in Calgary, Alberta with kidney biopsies performed between 2010 and 2020. Frozen kidney biopsies preserved in OCT (optimal cutting temperature) compound were subjected to immunohistochemistry to label EXT1 and 2. We then reviewed for correlation to renal function (serum creatinine) and proteinuria (urine protein to creatinine ratio) prior to biopsy, and up until 36 months post-biopsy.

Results

We detected both EXT1 and 2 in our cohort. Notably, we identified three distinct staining patterns. Negative/negative, positive/positive, and negative/positive, with respect to EXT1/EXT2 status. The pattern of negative/positive appears to be unique in comparison to previous studies with EXT1 and 2, which have shown uniform results between the two related proteins. Initial analyses show a trend towards resolving proteinuria for the EXT2 positive cohort.

Conclusion

Similar to prior reports using formalin fixed, paraffin embedded tissue, we demonstrate that frozen section staining can reliably detect EXT1/EXT2. Distinguishing EXT1/EXT2-positive patients may better predict outcomes with the potential to integrate into patient care. The significance of differential status between EXT 1 and 2 is yet to be determined but represents a distinctive finding that may assist in prognostication for this cohort.