| Autor: |
Alexander, Mariam P., Mangalaparthi, Kiran K., Madugundu, Anil K., Moyer, Ann M., Adam, Benjamin A., Mengel, Michael, Singh, Smrita, Herrmann, Sandra M., Rule, Andrew D., Cheek, E. Heidi, Herrera Hernandez, Loren P., Graham, Rondell P., Denic, Aleksander, Aubry, Marie-Christine, Roden, Anja C., Hagen, Catherine E., Quinton, Reade A., Bois, Melanie C., Lin, Peter T., Maleszewski, Joseph J., Cornell, Lynn D., Sethi, Sanjeev, Pavelko, Kevin D., Charlesworth, Jon, Narasimhan, Ramya, Larsen, Christopher P., Rizza, Stacey A., Nasr, Samih H., Grande, Joseph P., McKee, Trevor D., Badley, Andrew D., Pandey, Akhilesh, Taner, Timucin |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Mayo Clinic Proceedings |
| ISSN: |
1942-5546 |
| Popis: |
Objective To compare COVID-19 acute kidney injury (AKI) to sepsis-AKI (S-AKI) the morphology, transcriptomic and proteomic characteristics of autopsy kidneys were analyzed. Patients and methods Individuals 18 years and older who died from COVID-19 and had an autopsy performed at Mayo Clinic between April 2020 to October 2020 were included. Morphological evaluation of the kidneys of 17 individuals with COVID-19 was performed. In a subset of 7 COVID-19 cases with post-mortem interval of ≤20 hours, ultrastructural and molecular characteristics (targeted transcriptome & proteomics analyses of tubulointerstitium) were evaluated. Molecular characteristics were compared to archived cases of S-AKI and non-sepsis causes of AKI (NS-AKI). Results The spectrum of COVID-19 renal pathology included macrophage dominant microvascular inflammation (glomerulitis and peritubular capillaritis), vascular dysfunction (peritubular capillary congestion & endothelial injury), tubular injury with ultrastructural evidence of mitochondrial damage. Investigation of the spatial architecture using a novel imaging mass cytometry revealed enrichment of CD3+CD4+ T cells in close proximity to antigen-presenting cells, and macrophage-enriched glomerular and interstitial infiltrates, suggesting an innate and adaptive immune tissue response. COVID-19 AKI and S-AKI, as compared to NS-AKI, had an enrichment of transcriptional pathways involved in inflammation (apoptosis, autophagy, MHC class I and II, and Th1 differentiation). Proteomic pathway analysis demonstrated that COVID-19 AKI & to a lesser extent S-AKI was enriched in necroptosis and sirtuin signaling pathways, both involved in regulatory response to inflammation. Upregulation of ceramide signaling pathway and downregulation of oxidative phosphorylation in COVID-19 AKI was noted. Conclusions This data highlights the similarities between S-AKI and COVID-19 AKI and suggests that mitochondrial dysfunction may play a pivotal role in COVID-19 AKI. This data may allow the development of novel diagnostic and therapeutic targets. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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