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

NCT06412822 | Recruiting

• 1 other identifier: STONET's
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 2.to compare the NET/MET's concentrations in the urine with those in plasma

Conditions

Kidney Stone

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (2)

• Neutrophil extracellular traps (NETs) plasma levels

  24 hours

• Macrophages extracellular traps (MET's) plasma levels

  24 hours

Study Arms (2)

STONE group

Adult subjects with kidney stones disease

Other: Blood sampling; Other: Urine sampling

NON STONE group

Control group: patients with acute and/or chronic kidney disease (CKD) without stones

Other: Blood sampling; Other: Urine sampling

Interventions

Blood sampling OTHER

Blood sampling

NON STONE group; STONE group

Urine sampling OTHER

Urine sampling

NON STONE group; STONE group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brugmann University Hospital: lead

Study Sites (1)

CHU Brugmann

Brussels, 1020, Belgium

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

* plasma sample * serum sample * total blood EDTA for DNA * urine samples: 24h collections, fasting urine and 2nd morning urine

MeSH Terms

Conditions

Kidney Calculi

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Nephrolithiasis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urolithiasis; Urinary Calculi; Male Urogenital Diseases; Calculi; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Agnieszka POZDZIK

  CHU Brugmann

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Agnieszka POZDZIK

CONTACT

3224752639; Agnieszka.POZDZIK@chu-brugmann.be

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Nephrologist

Study Record Dates

• First Submitted: May 7, 2024
• First Posted: May 14, 2024
• Study Start: September 12, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: May 14, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)