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Acute Kidney Injury in Severe COVID-19 Has Similarities to Sepsis-Associated Kidney Injury: A Multi-Omics Study.
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; Aleksandar, Denic; 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.
  • Alexander MP; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. Electronic address: alexander.mariam@mayo.edu.
  • Mangalaparthi KK; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Institute of Bioinformatics, International Technology Park, Karnataka, India; Amrita School of Biotechnology, Kerala, India.
  • Madugundu AK; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Institute of Bioinformatics, International Technology Park, Karnataka, India; Manipal Academy of Higher Education, Manipal, Karnataka, India; Center for Molecular Medicine, National Institute of Mental Health and Neuro
  • Moyer AM; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Adam BA; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
  • Mengel M; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
  • Singh S; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Institute of Bioinformatics, International Technology Park, Karnataka, India; Manipal Academy of Higher Education, Manipal, Karnataka, India; Center for Molecular Medicine, National Institute of Mental Health and Neuro
  • Herrmann SM; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Rule AD; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Cheek EH; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Herrera Hernandez LP; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Graham RP; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Aleksandar D; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
  • Aubry MC; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Roden AC; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Hagen CE; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Quinton RA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Bois MC; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Lin PT; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Maleszewski JJ; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Cornell LD; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Sethi S; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Pavelko KD; Immune Monitoring Core, Mayo Clinic, Rochester, MN, USA.
  • Charlesworth J; Microscopy and Cell Analysis Core, Mayo Clinic, Rochester, MN, USA.
  • Narasimhan R; Department of Endocrinology, Mayo Clinic, Rochester, MN, USA.
  • Larsen CP; Nephropathology Associates, Little Rock, AR, USA.
  • Rizza SA; Division of Infectious Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
  • Nasr SH; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Grande JP; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • McKee TD; STTARR Innovation Core Facility, University Health Network, Toronto, Ontario, Canada.
  • Badley AD; Division of Infectious Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
  • Pandey A; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA; Center for Molecular Medicine, National Institute of Mental Health and Neurosciences, Karnataka, India.
  • Taner T; Department of Surgery (T.T.), Mayo Clinic, Rochester, MN, USA; Department of Immunology (T.T.), Mayo Clinic, Rochester, MN, USA.
Mayo Clin Proc ; 96(10): 2561-2575, 2021 10.
Article in English | MEDLINE | ID: covidwho-1521396
ABSTRACT

OBJECTIVE:

To compare coronavirus disease 2019 (COVID-19) acute kidney injury (AKI) to sepsis-AKI (S-AKI). The morphology and transcriptomic and proteomic characteristics of autopsy kidneys were analyzed. PATIENTS AND

METHODS:

Individuals 18 years of age 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 seven COVID-19 cases with postmortem interval of less than or equal to 20 hours, ultrastructural and molecular characteristics (targeted transcriptome and proteomics analyses of tubulointerstitium) were evaluated. Molecular characteristics were compared with archived cases of S-AKI and nonsepsis causes of AKI.

RESULTS:

The spectrum of COVID-19 renal pathology included macrophage-dominant microvascular inflammation (glomerulitis and peritubular capillaritis), vascular dysfunction (peritubular capillary congestion and endothelial injury), and 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. Coronavirus disease 2019 AKI and S-AKI, as compared to nonseptic AKI, had an enrichment of transcriptional pathways involved in inflammation (apoptosis, autophagy, major histocompatibility complex class I and II, and type 1 T helper cell differentiation). Proteomic pathway analysis showed that COVID-19 AKI and to a lesser extent S-AKI were enriched in necroptosis and sirtuin-signaling pathways, both involved in regulatory response to inflammation. Upregulation of the ceramide-signaling pathway and downregulation of oxidative phosphorylation in COVID-19 AKI were noted.

CONCLUSION:

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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Sepsis / Acute Kidney Injury / COVID-19 / Kidney Type of study: Risk factors Limits: Adult / Humans / Male / Middle aged Language: English Journal: Mayo Clin Proc Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Sepsis / Acute Kidney Injury / COVID-19 / Kidney Type of study: Risk factors Limits: Adult / Humans / Male / Middle aged Language: English Journal: Mayo Clin Proc Year: 2021 Document Type: Article