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

June 24, 2024 updated by: Jesus Rivero, MD, Instituto Nacional de Enfermedades Respiratorias

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.

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Actual)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Ciudad DE México
      • Mexico City, Ciudad DE México, Mexico, 14080
        • National Institute of Respiratory Diseases

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

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).

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • Specimens with sub-optimal quality for analysis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fibrosis and sclerosis scores for identifying morphological changes in kidney tissue.
Time Frame: From the date of postmortem kidney biopsy until the date of histopathological report, in average seven days.
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.
Time Frame: From the date of arrival at the hospital until the date of death, in average one month.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Differential gene expression using polymerase chain reaction
Time Frame: From the date of postmortem kidney biopsy until the date of measure of differential gene expression, evaluated in 72 months.
Changes in differential gene expression in the kidney tissue of patients who died from due to severe COVID-19.
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.
Time Frame: From the date of postmortem kidney biopsy until the date of measure the inflammatory molecules expressed in the tissue, evaluated in 72 months.
Changes in the quantity of inflammatory molecules in the kidney tissue of patients who died due to severe COVID-19.
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.
Time Frame: 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.
Changes in the quantity of oxidative stress molecules expressed in the kidney tissues of patients who died due to severe COVID-19.
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.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Content of proteins
Time Frame: At the time of death
Changes in the content of proteins in the kidney tissue of patients who died from severe COVID-19.
At the time of death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Enfermedades Respiratorias

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 30, 2020

Primary Completion (Actual)

December 31, 2020

Study Completion (Actual)

October 8, 2023

Study Registration Dates

First Submitted

June 3, 2024

First Submitted That Met QC Criteria

June 3, 2024

First Posted (Actual)

June 6, 2024

Study Record Updates

Last Update Posted (Actual)

June 27, 2024

Last Update Submitted That Met QC Criteria

June 24, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C-5920

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on COVID-19

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Peru

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe