Morphofunctional, Gene, Inflammation Molecules and Oxidative Stress Analysis in Kidney Tissue of COVID-19 Patients

NCT06444893 | Completed DMC

• 1 other identifier: C-5920
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

COVID-19; Kidney Injury; Gene Amplification; Oxidative Stress; Inflammatory Response

Outcome Measures

Primary Outcomes (2)

• Fibrosis and sclerosis scores for identifying morphological changes in kidney tissue.

  Morphological changes were evaluated by the fibrosis and sclerosis scores (mild, moderate and severe), using direct visualization of nephron compartments (glomerular and tubulointerstitial) of patients who died due to severe COVID-19.

  From the date of postmortem kidney biopsy until the date of histopathological report, in average seven days.

• The estimated glomerular filtration rate for evaluating functional changes. The estimated glomerular filtration rate for evaluating functional changes.

  Functional changes were calculated using the estimated glomerular filtration rate (\> 60 vs \< 60 ml/min/1.73m2) of patients who died due to severe COVID-19.

  From the date of arrival at the hospital until the date of death, in average one month.

Secondary Outcomes (3)

• Differential gene expression using polymerase chain reaction

  From the date of postmortem kidney biopsy until the date of measure of differential gene expression, evaluated in 72 months.

• Quantity of inflammatory molecules expressed in picograms of proteins.

  From the date of postmortem kidney biopsy until the date of measure the inflammatory molecules expressed in the tissue, evaluated in 72 months.

• Quantity of oxidative stress molecules expressed in picograms of proteins.

  From the date of postmortem kidney biopsy to the date of measure of oxidative stress molecules expressed in the tissue report, evaluated in 72 months.

Eligibility Criteria

• Age: 15 Years - 80 Years
• Gender Eligibility Details: The investigators chose only males for the study due to they presented a major deleterious effect in scientific literature.
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults \>15 years old who died at the INER with a confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

You may qualify if:

• Not having at least one creatinine measurement.
• Family members will not accept to participate.

You may not qualify if:

• Specimens with sub-optimal quality for analysis.

Sponsors & Collaborators

• Instituto Nacional de Enfermedades Respiratorias: lead

Study Sites (1)

National Institute of Respiratory Diseases

Mexico City, Mexico City, 14080, Mexico

Location

Biospecimen

Retention: SAMPLES WITH DNA

kidney biopsies of deceased patients with COVID-19

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: June 6, 2024
• Study Start: March 30, 2020
• Primary Completion: December 31, 2020
• Study Completion: October 8, 2023
• Last Updated: June 27, 2024

Record last verified: 2024-06

Locations

ME (1)