Role of NGAL and Cystatin C in Prediction of Acute Kidney Injury Covid-19 Infection

Role of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Cystatin C in Prediction of Acute Kidney Injury in Patients With Covid-19 Infection

Recent different biomarkers of acute kidney injury (AKI) have been manufactured by pharmaceutical industry. Studies proved that Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin c are effective predictive biomarkers for early acute kidney injury in septic patients and in children after cardiopulmonary bypass. This study hypothesize that both cystatin c and Neutrophil gelatinase-associated lipocalin can predict AKI in patients with COVID-19 before elevation of serum urea and creatinine which may help early interference.

Study Overview

• Status: Completed
• Conditions: Biochemical Markers ,NGAL,Cystatin c, Acute Kidneyinjury, Covid 19
• Intervention / Treatment: Diagnostic test: serum NGAL and cystatin c

Detailed Description

Since December 2019, a novel coronavirus called SARSCoV-2 (severe acute respiratory syndrome coronavirus 2) has caused an international outbreak of respiratory illness described as COVID-19. Among 85 patients with COVID-19 an incidence of acute kidney injury was reported to be 23%. The kidney histology from autopsies of six patients showed severe acute tubular necrosis with macrophage and lymphocyte infiltration. Another important paper revealed prominent acute proximal tubular injury, accumulation of peritubular erythrocyte and glomerular fibrin microthrombi after autopsy. However, this kidney injury was not detected by routine measures (creatinine and/or BUN) in some patients denoting subclinical kidney injury. The pathophysiology of AKI associated with COVID-19 could be due to specific mechanisms such as direct cell injury from viral entrance through highly expressed renal ACE2 receptors. Also pro-inflammatory cytokines, an imbalanced renin-angotensin-aldosterone system and thrombotic events are accused in renal damage. Non-specific mechanisms include hypovolemia, haemodynamic changes, right heart failure, high levels of PEEP in mechanically ventilated patients, nephrotoxic drugs and nosocomial infections. A significant association between kidney failure and death was documented in five studies. Hypoxemia and impairment of gas exchange has been identified as elements associated with AKI in patients with acute respiratory distress syndrome (ARDS).

Studies focusing on AKI with COVID-19 are needed urgently in order to identify the mechanism of renal affection and to predict the risk of AKI. Pharmaceutical industries with academia have made a lot of progress in the field of sensitive and specific preclinical biomarkers of kidney injury. Neutrophil gelatinase-associated lipocalin (NGAL) is composed of 178 amino acids. this glycoprotein is reabsorbed in the proximal tubules after its filtration through the glomeruli.

In a mouse model of renal ischemia, NGAL gene was rapidly expressed and upregulated within 3 hours of injury. The NGAL mRNA level increased more than 1000-fold 24-48 hours after injury. Thus, NGAL can be a useful tool to diagnose infection mediated AKI. Nonglycosylated Cystatin C is a protein produced by nucleated cells at constant rate. It is easily filtered through the glomeruli due to its positive charge at physiological pH and its low molecular weight. Then, it is reabsorbed and completely catabolized in the proximal tubules. Use of serum cystatin C as a marker of glomerular filtration rate (GFR) is well documented, and some authors have suggested that it may be more accurate than serum creatinine for this purpose. Complete evaluation of the clinical and laboratory picture of COVID-19 associated AKI is crucial to design preventive strategies and to suggest targeted interventions

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11591
    • Ainshams hospitals
  • New Cairo, Egypt, 11865
    • Sanaa Wasfy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

adult patients from 18-85 diagnosed as covid 19 infection by nasaopharyngeal swap

Description

Inclusion Criteria:

• person with the one of the following symptoms: fever and respiratory symptoms with radiological findings of pneumonia compatible with COVID-19

  1. Respiratory distress (≥ 30 breaths/ min);
  2. Oxygen saturation ≤ 93% at rest;
  3. Arterial partial pressure of oxygen (PaO2)/ fraction of inspired oxygen (FIO2) ≤ 300.
  4. Cases with chest imaging that shows obvious lesion progression within 24-48 hours > 50%.
  5. Respiratory failure and requiring mechanical ventilation;
  6. Shock;
  7. other organ failure that requires ICU care.

Exclusion Criteria:

• patients classified as mild corona virsus disease, patients with end-stage renal disease (ESRD) or on chronic regular dialysis, presence of AKI and anuria at the time of ICU admission, history of chronic kidney disease, severe urinary tract infection, kidney malignancy, and renal transplantation.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
study group; blood sampling and measduring of serum NGAL and cystatin c on admission and after 48 hours and creatinine every day	Diagnostic test: serum NGAL and cystatin c; measuring serum NGAL and cystatin c on admission and after 48 hours in critically ill patients with covid 19 then compare results to serum creatinine and signs of acute kidney injury

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
measure both cystatin c and Neutrophil gelatinase-associated lipocalin on admission and after 48 hours. (NGAL) as recent biomarkers in prediction of AKI in patients with COVID-19.	biochmical tests for detection of NGAL and Cystatin c in crirically ill Covid 19 patients	12 days starting from hospital admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
development of acute kidney injury lipocalin (NGAL) to AKI severity and prognosis of AKI in patients with COVID-19 infection	increased serum creatinine	12 days starting from day of admission

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: sanaa wasfy, lecturer

Publications and helpful links

General Publications

• Darmon M, Schortgen F, Leon R, Moutereau S, Mayaux J, Di Marco F, Devaquet J, Brun-Buisson C, Brochard L. Impact of mild hypoxemia on renal function and renal resistive index during mechanical ventilation. Intensive Care Med. 2009 Jun;35(6):1031-8. doi: 10.1007/s00134-008-1372-5. Epub 2009 Feb 26.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: October 17, 2020
• First Submitted That Met QC Criteria: October 23, 2020
• First Posted (Actual): October 27, 2020

Study Record Updates

• Last Update Posted (Actual): September 13, 2021
• Last Update Submitted That Met QC Criteria: September 4, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency; COVID-19; Acute Kidney Injury; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Cysteine Proteinase Inhibitors; Cystatins
• Other Study ID Numbers: FMASU P82b/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No