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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