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Digital spatial profiling of collapsing glomerulopathy.

Kelly D Smith1, David K Prince2, Kammi J Henriksen3

  • 1Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA; Kidney Research Institute, Seattle, Washington, USA.

Kidney International
|March 1, 2022
PubMed
Summary
This summary is machine-generated.

Digital spatial profiling (DSP) revealed hidden gene expression differences in collapsing glomerulopathy, a kidney disease often caused by viruses like HIV or SARS-CoV-2. This advanced technique offers new insights into disease mechanisms.

Keywords:
COVID-19–associated nephropathyHIV-associated nephropathycollapsing glomerulopathydigital spatial profilingkidney biopsykidney pathology

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Area of Science:

  • Nephrology
  • Molecular Biology
  • Pathology

Background:

  • Collapsing glomerulopathy, a severe form of focal and segmental glomerulosclerosis, is characterized by heavy proteinuria and poor prognosis.
  • Viral infections, including HIV and SARS-CoV-2, can trigger collapsing glomerulopathy.
  • Understanding the molecular mechanisms driving heterogeneity in collapsing glomerulopathy is challenging due to limited affected glomeruli per biopsy.

Purpose of the Study:

  • To investigate the transcriptional heterogeneity within glomeruli of patients with collapsing glomerulopathy using digital spatial profiling (DSP).
  • To compare glomerular transcriptional profiles in collapsing glomerulopathy triggered by HIV versus SARS-CoV-2.
  • To evaluate DSP as a method for dissecting transcriptional programs in kidney lesions.

Main Methods:

  • Digital spatial profiling (DSP) was employed to quantify mRNA expression of 1,852 transcripts in individual glomeruli.
  • Samples included glomeruli from kidney biopsies of patients with HIV or SARS-CoV-2-associated collapsing glomerulopathy and control biopsies.
  • Immunohistochemistry and RNA in situ hybridization were used for focused validation of DSP findings.

Main Results:

  • DSP uncovered significant intra- and inter-patient heterogeneity in glomerular transcriptional profiles, which were previously undetected.
  • Histologically similar collapsing glomeruli across HIV and SARS-CoV-2 groups exhibited distinct molecular signatures.
  • DSP results showed good concordance with validation techniques like immunohistochemistry and RNA in situ hybridization.

Conclusions:

  • Digital spatial profiling (DSP) is a powerful technology for dissecting transcriptional heterogeneity in kidney diseases like collapsing glomerulopathy.
  • DSP provides higher resolution insights into glomerular gene expression compared to traditional methods.
  • This approach can advance the understanding of molecular mechanisms underlying pathologically discernible kidney lesions.