ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: PO1900

A Target Antigen-Based Approach to the Classification of Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Bobart, Shane A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Tehranian, Shahrzad, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Sethi, Sanjeev, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Alexander, Mariam P., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Nasr, Samih H., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Vrana, Julie A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Said, Samar M., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Giesen, Callen D., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Fervenza, Fernando C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • De Vriese, An S., AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium
Background

Primary membranous nephropathy (MN) is caused by circulating auto-antibodies against podocyte surface antigens, identified as M-type-phospholipase–A2-receptor (PLA2R) in 70-80% and thrombospondin-type-1-domain-containing-7A (THSD7A) in 2-5% of patients. Secondary MN occurs in the context of malignancy, auto-immune disease, infection, paraproteinemia or medication. Some patients with PLA2R-associated MN have a current or previously diagnosed associated condition, but it remains unclear whether it is causally related or coincidental. A few THSD7A-associated MN cases have a strong etiologic link with active malignancy, while in others malignancy appears coincidental. Exostosin 1/exostosin 2 (EXT1/EXT2) are recently discovered target antigens in patients with MN, the majority of whom have auto-immune disease. These recent findings blur the traditional distinction between primary and secondary MN.

Methods

To describe the phenotypes of PLA2R-, THSD7A- and EXT1/EXT2-associated MN, 201 adult patients with biopsy-proven MN were classified using serology, immunostaining and mass spectrometry. Clinical, biochemical and follow-up data were examined for associated disease and its relationship with MN.

Results

PLA2R-associated MN (n=161) occurred predominantly in middle-aged white males, with 72% presenting without associated disease. Only 1 case of THSD7A-associated MN was identified, with a concomitant malignancy. EXT1/EXT2-associated MN (n=8) was identified in younger females and was strongly linked with active auto-immunity. The majority of patients who were negative for all three target antigens (n=27/31, 87%) presented with associated disease, mainly malignancy and auto-immunity.

Conclusion

In conclusion, the historical primary-secondary dichotomy has substantial limitations when applied to MN. We propose a terminology combining the target antigen involved in pathogenesis and the associated clinical diseases in order to classify MN and guide clinical decision making.

Funding

  • Private Foundation Support