期刊
KIDNEY INTERNATIONAL
卷 101, 期 5, 页码 1017-1026出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2022.01.033
关键词
collapsing glomerulopathy; COVID-19-associated nephropathy; digital spatial profiling; HIV-associated nephropathy; kidney biopsy; kidney pathology
资金
- Department of Laboratory Medicine and Pathology at the University of Washington
- National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK130386]
- NIH/National Center for Advancing Translational Sciences [UG3/UH3TR002158-04S1]
Collapsing glomerulopathy is a histologically distinct variant of focal and segmental glomerulosclerosis that presents with heavy proteinuria and poor prognosis. This disease can be triggered by viral infections such as HIV or SARS-CoV-2. Digital spatial profiling (DSP) technology provides a powerful method to analyze the transcriptional programs of pathologically discernible kidney lesions.
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 or SARS-CoV-2. Transcriptional profiling of collapsing glomerulopathy lesions is difficult since only a few glomeruli may exhibit this histology within a kidney biopsy and the mechanisms driving this heterogeneity are unknown. Therefore, we used recently developed digital spatial profiling (DSP) technology which permits quantification of mRNA at the level of individual glomeruli. Using DSP, we profiled 1,852 transcripts in glomeruli isolated from formalin fixed paraffin embedded sections from HIV or SARS-CoV-2-infected patients with biopsy-confirmed collapsing glomerulopathy and used normal biopsy sections as controls. Even though glomeruli with collapsing features appeared histologically similar across both groups of patients by light microscopy, the increased resolution of DSP uncovered intra- and interpatient heterogeneity in glomerular transcriptional profiles that were missed in early laser capture microdissection studies of pooled glomeruli. Focused validation using immunohistochemistry and RNA in situ hybridization showed good concordance with DSP results. Thus, DSP represents a powerful method to dissect transcriptional programs of pathologically discernible kidney lesions.
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