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Morphofunctional Analysis, Gene Expression of Inflammation Molecules and Response Mechanisms to Oxidative Stress in Kidney Tissue of Deceased Patients With COVID-19: "Ancestral Variant"
The involvement of the kidneys in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the outset of the pandemic was associated with high mortality rates worldwide. This was in part due to the generation of an inflammatory process and exacerbated oxidative stress. The present study was initiated to investigate the relationship between morphofunctional changes and gene expression in the kidney tissue of deceased Mexican patients prior to the initiation of vaccination. The investigator designed a single-center, prospective, cohort study, to analyze and relate the morphofunctional changes and gene expression of inflammatory and oxidative stress molecules in the kidney tissue of men who died from severe COVID-19. A total of 40 percutaneous renal biopsies from deceased patients with severe acute respiratory syndrome coronavirus 2 infection were included in the study and divided into two a groups. One group was preserved in trizol to obtain RNA and total protein, while the remaining sample was fixed in formalin to be examined by staining with hematoxylin and eosin. The histopathological analysis was conducted by an experienced pathologist. The expression of molecules was evaluated by real-time polymerase chain reaction assay (nphs2, slc9a1, cx3cl1, havcr1, slc22a17, sod2, egf, timp2, hmox1, fabp1, and so forth). The following biomarkers were analyzed: interleukin-6, Arginase-1 (Arg-1), Dipeptidyl peptidase-4 (DPP-4), GSTT1, type I gamma-glutamyltransferase (GGT1), Occludin (OCL), CYP3A4, and Claudin-8 (CL-8). Additionally, Western blot analysis was conducted on claudin-5 (CL-5), occludin, HSP70, Nuclear factor erythroid 2-related factor-2 (NRF-2), superoxide dismutase-2 (SOD-2), nicotinamide adenine dinucleotide phosphate dehydrogenase 1 (NQO1), Gamma glutamylcysteine synthase (γ-GCL), and receptor for advanced glycation end products (RAGE). The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, with the subjects divided into two groups based on their eGFR: \>60 or \<60 ml/min/1.73 m². The statistical analysis was conducted using the Stata program and GraphPad software, version 10.2.3.
Age
15 - 80 years
Sex
MALE
Healthy Volunteers
No
National Institute of Respiratory Diseases
Mexico City, Mexico City, Mexico
Start Date
March 30, 2020
Primary Completion Date
December 31, 2020
Completion Date
October 8, 2023
Last Updated
June 27, 2024
40
ACTUAL participants
Lead Sponsor
Instituto Nacional de Enfermedades Respiratorias
NCT05806645
NCT06082518
Data Source & Attribution
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