Abstract: PO1665
Spatial Transcriptomic Profiling of Collapsing Glomerulopathy
Session Information
- Podocyte Injury in Human Disease: Pathomechanism, Diagnosis, and Therapy
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
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