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: PO1665

Spatial Transcriptomic Profiling of Collapsing Glomerulopathy

Session Information

Category: Glomerular Diseases

  • 1204 Podocyte Biology

Authors

  • Akilesh, Shreeram, University of Washington, Seattle, Washington, United States
  • Henriksen, Kammi J., University of Chicago Pritzker School of Medicine, Chicago, Illinois, United States
  • Nicosia, Roberto F., University of Washington, Seattle, Washington, United States
  • Alpers, Charles E., University of Washington, Seattle, Washington, United States
  • Smith, Kelly D., University of Washington, Seattle, Washington, United States
Background

Collapsing glomerulopathy is a histologically distinct variant of focal and segmental glomerulosclerosis that presents with heavy proteinuria and portends a poor prognosis. Collapsing glomerulopathy can be triggered by viral infections such as HIV and SARS-CoV-2. However, it is not known if distinct molecular mechanisms drive histologically indistinguishable lesions of collapsing glomerulopathy in different clinical contexts.

Methods

Transcriptional profiling of collapsing glomerulopathy lesions is difficult since only a few glomeruli may exhibit this histology within a kidney biopsy. Therefore, we used recently developed spatial transcriptional profiling to quantify 1,852 transcripts in individual glomeruli from HIV and SARS-CoV-2 infected patients with biopsy confirmed collapsing glomerulopathy.

Results

We compared transcriptional signatures on the basis of disease or histology and identified distinct pathways of injury in HIV and SARS-CoV-2 associated collapsing glomerulopathy and thrombotic microangiopathy (Figure). Focused validation using immunohistochemistry and RNA in situ hybridization showed good concordance with spatial transcriptional profiling results.

Conclusion

Spatial transcriptional profiling represents a powerful new method to dissect transcriptional programs of pathologically discernible kidney lesions.

Funding

  • Other NIH Support