Renal Biomarkers in AKI and COVID-19

Acute Kidney Injury In Subjects With Severe Acute Respiratory Syndrome Due to SARS-CoV2 Infection

Severe pneumoniae related to Coronavirus Disease (COVID-19), had a high in-hospital mortality; this condition are worst in subjects with acute kidney disease (AKI); conditioning increased mortality, days of assisted mechanical ventilation (AMV), increased nosocomial infections and high costs. We need many studies for determinated the risk factors for AKI in subjects with COVID-19.

This study pretends identify the incidence of AKI in subjects with severe pneumoniae by COVID-19, describe the role of some biomarkers in the physiopathology of AKI-COVID-19; and determine the evolution of urinary biomarkers during hospitalization, like neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP7), and interleukin-6 (IL-6) and the progression of viruria of Severe Acute Respiratory Syndrome (SARS) related to CoronaVirus 2 (CoV2) in subjects with or without AKI.

Study Overview

• Status: Completed
• Conditions: Coronavirus Infection; Covid19; AKI; SARS (Severe Acute Respiratory Syndrome)
• Intervention / Treatment: Diagnostic test: urinary NGAL, TIMP-2, IGFBP7, IL-6, viral load and metabolomic

Detailed Description

The usefulness of urinary NGAL levels and the platelet / lymphocyte index as predictive markers of AKI in the context of COVID-19 will be studied. These results will allow to propose more appropriate strategies for the prevention, diagnosis and timely management of patients with severe pneumonia due to COVID-19 and AKI. Knowing the viral load in urine and its evolution in patients with and without AKI will allow us to explore associations between the presence of the virus at the local level and the presence of kidney damage. Likewise, the presence of viral load in urine and its possible relationship with the local activation of the complement system, together with the detection of biomarkers of kidney damage, like NGAL, TIMP-2, IGFBP7, and IL-6, will allow us to better understand the pathophysiology of these alterations in the context of COVID-19; additionally, some patients received tocilizumab, an IL-6 inhibitor as a compassionate measure, which may reduce urinary levels of interleukins and other inflammatory markers.

Finally, the study of possible differences in the metabolome in urine in patients with and without acute kidney injury could favor the discovery of new markers to identify patients with SARS-CoV-2 infection susceptible to the development of AKI.

Determine the evolution of NGAL, TIMP-2, IGFBP7, IL-6, viral load and metabolomic basal, and the days 3 , 5 and 7 after recruitment

• Study Type: Observational
• Enrollment (Actual): 51

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 14060
    • Centro de Investigacion en Enfermedades Infecciosas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Older adults were recruited, with a diagnosis of COVID-19 confirmed by PCR, in their first 48 hours of hospitalization that meet severity criteria, with 5 to 7 degrees of severity according to the WHO classification.

Description

Inclusion Criteria:

• Subjects over 18 years of age.
• Subjects admitted with a diagnosis of probable SARS-CoV-2 pneumonia.
• Subjects with a diagnosis of SARS-CoV-2 pneumonia confirmed by Real-time quantitative-Polymerase Chain Reaction (qRT-PCR).
• Subjects with qRT-PCR negative for SARS-CoV-2, but who meet clinical and radiological criteria for COVID-19, and no other causes have been identified.

Exclusion Criteria:

• Pregnant women
• Incomplete medical records.

Elimination criteria:

• Patients who die within the first 24 hours of entering the institute.
• Patients discharged for any reason not considered death within the first 48 hours, such as voluntary discharge or transfer to other health institutions.
• Patients who during their hospitalization report a positive PCR for other non-respiratory viruses without identifying SARS-CoV-2
• Patients who withdraw their consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Severe pneumoniae; Evaluate the progression to AKI during first 30 days of recruitment	Diagnostic test: urinary NGAL, TIMP-2, IGFBP7, IL-6, viral load and metabolomic; Determine the evolution of NGAL, TIMP-2, IGFBP7, IL-6, viral load and metabolomic at basal, and the 3 , 5 and 7 days after recruitment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary levels of renal biomarkers	To estimate the strength of association between the elevation of urinary levels of NGAL, TIMP-2, IGFBP7 and IL-6 and the development of AKI associated with SARS-CoV-2 pneumonia	Seven days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of AKI	Describe the incidence of AKI in critically ill patients with severe COVID-19 pneumonia	One month
Urinary levels of renal biomarkers and mortality	Estimate the strength of association of elevated urinary levels of NGAL, TIMP-2, IGFBP7 and IL-6 with mortality	30 days
Urinary levels of renal biomarkers and severity of the disease.	Estimate the strength of association of elevated urinary levels of NGAL, TIMP-2, IGFBP7 and IL-6 with teh severity of the disease.	30 days
Risk factors for AKI in severe COVID-19	Identify possible risk factors (epidemiological, clinical, paraclinical, use of nephrotoxic agents) for the development of AKI in critically ill patients with COVID-19 pneumonia.	30 days
Evolution renal biomarkers	Compare the evolution over time of renal function markers (NGAL, TIMP-2 and IGFBP7) in patients with and without kidney injury.	7 days
Evolution of viral load	Compare the evolution over time of the SARS-CoV-2 viral load in patients with and without acute kidney injury.	7 days
Evolution of complement pathway	Analyze the complement pathway in urine and compare its evolution over time in patients with and without acute kidney injury and SARS-CoV-2 infection.	seven days
Metabolomic profile	Analyze the metabolomic profile in urine in patients with and without acute kidney injury with SARS-CoV-2 infection.	7 days
Respiratory changes	Describe partial arterial oxygen concentration/inspired oxygen faction (PaO2/FiO2) ratio and radiologic evolution in patients with severe SARS COV2 pneumonia.	30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nosocomial Infections	Stablish the nosocomial infections in subjects with or without AKI	30 days

Collaborators and Investigators

• Sponsor: Instituto Nacional de Enfermedades Respiratorias
• Investigators: Principal Investigator: Santiago Avila Rios, PhD, Instituto Nacional De Enfermedades Respiratorias

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): September 30, 2020
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: August 15, 2020
• First Submitted That Met QC Criteria: August 15, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: June 4, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19; AKI; SARS; METABOLOMIC; KIDNEY BIOMARKERS
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease; Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections; Syndrome; Infections
• Other Study ID Numbers: C26-20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No