Neutrophil Extracellular Traps (NET's) in Prevalent Kidney Stone

Neutrophil Extracellular Traps (NET's) in Prevalent Kidney Stone, Cross-section, Non-drug Clinical Study-Analysis of Biological Fluids (Residual Human Body Material (RHBM)): STONET's Project

Neutrophils are first responders to any kind of threat the body faces: infection, severe trauma, cancer, surgery... They produce the cytokines, induct oxidative stress and de-granulate toxic proteins to kill pathogens. However the new mechanism related to the neutrophil extracellular traps release has been recognized as a new way of cell necrosis and has been called a NETosis.

NETosis is a hugely important new mechanism of human immune responses also described in various forms of acute kidney injury (ischemic, toxic, autoimmune). In certain kidney diseases, neutrophils release NETs and induce cell necrosis. Whether neutrophils die along with NET release, and if they do die, remains under study and is most likely context dependent. Extracellular traps (ETs) can be released also by macrophages. The ETs formation as well as macrophages extracellular traps (MET's) especially in kidney disease are cytotoxic and elicit inflammation, contributing to necro-inflammation of the early-injury phase of acute tubular necrosis in anti-neutrophil cytoplasmic antibody-related renal vasculitis, anti-glomerular basement membrane disease, lupus nephritis. Finally, acute kidney injury-related releases of dying renal cells or ETs promote organ injuries - for example, acute respiratory distress syndrome. According to the recent review the term 'NET formation' has been proposed as a better term to use instead of 'NETosis'. The formation of neutrophil extracellular traps (NETs) has been recently recognized as a unique modality of pathogen fixation (sticky extracellular chromatin) and pathogen killing (cytotoxic histones and proteases) during host immune responses, as well as collateral tissue damage.

Histones are potent mediators of injury in various cells. Indeed, extracellular histone induce microvascular endothelial cells and renal epithelial cells death in vitro, forms the pores that disrupt cell integrity and induce the cytolysis by their capacity of binding with membrane phospholipids and activation of inflammasome in the kidney leading to auto-entrainment of inflammation.

The activation of inflammation has been demonstrated in the experimental model of crystalline nephropathy related to the uncontrolled oxalate urinary excretion. Inhibition of inflammasome activation has been related with the preservation of kidney function. In patients with kidney stone disease the presence of crystals in the urine has been demonstrated to induce tubular epithelial cells injury that can theoretically trigger the NET's or MET's release and tissue inflammation.

NETs are now increasingly described as new targets for therapies, however largely under-estimated.

The role of release of ETs from neutrophils and macrophages during the kidney stone disease has never been studied in urine but the neutrophil extracellular trap (NET) formation-NETosis - was found significantly increased in the papillae of patients with brushite stones compared with CaOx stones.

The key objectives of this study are:

1. to assess NET/MET's excretion in the urine as a non-invasive method of NET/MET'osis measurement in patients with kidney diseases as a new biomarker of early stage of cells damages reflecting kidney injury occurring in patients with uncontrolled stones and other renal diseases;
2. to compare the NET/MET's concentrations in the urine with those in plasma

Study Overview

• Status: Recruiting
• Conditions: Kidney Stone
• Intervention / Treatment: Other: Blood sampling; Other: Urine sampling

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Agnieszka POZDZIK; Phone Number: 3224752639; Email: Agnieszka.POZDZIK@chu-brugmann.be

Study Locations

• Belgium
  • Brussel, Belgium, 1020
    • Recruiting
    • CHU Brugmann
    • Contact: Agnieszka Pozdzik, MD,PhD; Phone Number: +32 (0)2 4752639; Email: agnieszka.pozdzik@chu-brugmann.be
    • Principal Investigator: Agnieszka Pozdzik, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with acute and/or chronic kidney disease, with stones or without stones, ambulatory or hospitalized in CHU Brugmann Brugmann.

Description

Inclusion Criteria:

- Patients with acute and/or chronic kidney disease, with stones or without stones, ambulatory or hospitalized in CHU Brugmann Brugmann.

Exclusion Criteria:

• Malignancy or treatment for malignancy within 12 months prior to Screening with the exception of localized basal cell or squamous cell skin cancer. Note: Subjects whose malignancy is in remission and who are on a stable dose of chronic suppressive or maintenance therapy are not excluded.
• Psychological illness or condition, interfering with the patient's compliance or ability to understand the requirements of the study.
• Participation in another clinical trial.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
STONE group; Adult subjects with kidney stones disease	Other: Blood sampling; Blood sampling; Other: Urine sampling; Urine sampling
NON STONE group; Control group: patients with acute and/or chronic kidney disease (CKD) without stones	Other: Blood sampling; Blood sampling; Other: Urine sampling; Urine sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil extracellular traps (NETs) excretion in 24h urine collection	Assessment of NET excretion in 24h urine collection	24 hours
Neutrophil extracellular traps (NETs) excretion in fasting urine	Assessment of NET excretion in fasting urine	24 hours
Neutrophil extracellular traps (NETs) excretion in 2e morning urine	Assessment of NET excretion in 2e morning urine	24 hours
Macrophages extracellular traps (MET's) excretion in 24h urine collection	Assessment of MET's in 24h urine collection	24 hours
Macrophages extracellular traps (MET's) excretion in fasting urine	Assessment of MET's in fasting urine	24 hours
Macrophages extracellular traps (MET's) excretion in 2e morning urine	Assessment of MET's in 2e morning urine	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil extracellular traps (NETs) plasma levels	Neutrophil extracellular traps (NETs) plasma levels	24 hours
Macrophages extracellular traps (MET's) plasma levels	Macrophages extracellular traps (MET's) plasma levels	24 hours

Collaborators and Investigators

• Sponsor: Brugmann University Hospital
• Investigators: Principal Investigator: Agnieszka POZDZIK, CHU Brugmann

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: May 7, 2024
• First Submitted That Met QC Criteria: May 13, 2024
• First Posted (Actual): May 14, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Urolithiasis; Urinary Calculi; Calculi; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Calculi; Nephrolithiasis
• Other Study ID Numbers: STONET's

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