## Protocol Section
### Identification Module
**NCT ID:** NCT06412822

**Brief Title:** Neutrophil Extracellular Traps (NET's) in Prevalent Kidney Stone

**Official Title:** 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

#### Organization Study ID Info
**ID:** STONET's
#### Organization
**Class:** OTHER
**Full Name:** Brugmann University Hospital
### Status Module
#### Completion Date
**Date:** 2024-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-14

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-13

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-09-12

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-14
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-07
**Study First Submit QC Date:** 2024-05-13
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Brugmann University Hospital

#### Responsible Party

**Investigator Affiliation:** Brugmann University Hospital

**Investigator Full Name:** Agnieszka Pozdzik

**Investigator Title:** Nephrologist

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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. 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

### Conditions Module

**Conditions:**

- Kidney Stone

### Design Module

#### Bio Spec

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

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** CASE_CONTROL

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 500

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Adult subjects with kidney stones disease

**Intervention Names:**

- Other: Blood sampling

- Other: Urine sampling

**Label:** STONE group

#### Arm Group 2

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

**Intervention Names:**

- Other: Blood sampling

- Other: Urine sampling

**Label:** NON STONE group

### Interventions

#### Intervention 1

**Arm Group Labels:**

- NON STONE group

- STONE group

**Description:** Blood sampling

**Name:** Blood sampling

**Type:** OTHER

#### Intervention 2

**Arm Group Labels:**

- NON STONE group

- STONE group

**Description:** Urine sampling

**Name:** Urine sampling

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Assessment of NET excretion in 24h urine collection

**Measure:** Neutrophil extracellular traps (NETs) excretion in 24h urine collection

**Time Frame:** 24 hours

**Description:** Assessment of NET excretion in fasting urine

**Measure:** Neutrophil extracellular traps (NETs) excretion in fasting urine

**Time Frame:** 24 hours

**Description:** Assessment of NET excretion in 2e morning urine

**Measure:** Neutrophil extracellular traps (NETs) excretion in 2e morning urine

**Time Frame:** 24 hours

**Description:** Assessment of MET's in 24h urine collection

**Measure:** Macrophages extracellular traps (MET's) excretion in 24h urine collection

**Time Frame:** 24 hours

**Description:** Assessment of MET's in fasting urine

**Measure:** Macrophages extracellular traps (MET's) excretion in fasting urine

**Time Frame:** 24 hours

**Description:** Assessment of MET's in 2e morning urine

**Measure:** Macrophages extracellular traps (MET's) excretion in 2e morning urine

**Time Frame:** 24 hours

#### Secondary Outcomes

**Description:** Neutrophil extracellular traps (NETs) plasma levels

**Measure:** Neutrophil extracellular traps (NETs) plasma levels

**Time Frame:** 24 hours

**Description:** Macrophages extracellular traps (MET's) plasma levels

**Measure:** Macrophages extracellular traps (MET's) plasma levels

**Time Frame:** 24 hours

### Eligibility Module

**Eligibility Criteria:** 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.

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

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

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Agnieszka.POZDZIK@chu-brugmann.be

**Name:** Agnieszka POZDZIK

**Phone:** 3224752639

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Brussel

**Contacts:**

***Contact 1:***

- **Email:** agnieszka.pozdzik@chu-brugmann.be

- **Name:** Agnieszka Pozdzik, MD,PhD

- **Phone:** +32 (0)2 4752639

- **Role:** CONTACT

***Contact 2:***

- **Name:** Agnieszka Pozdzik, MD,PhD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** Belgium

**Facility:** CHU Brugmann

**Status:** RECRUITING

**Zip:** 1020

#### Overall Officials

**Official 1:**

**Affiliation:** CHU Brugmann

**Name:** Agnieszka POZDZIK

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000002137

- Term: Calculi

- ID: D000020763

- Term: Pathological Conditions, Anatomical

- ID: D000007674

- Term: Kidney Diseases

- ID: D000014570

- Term: Urologic Diseases

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000052878

- Term: Urolithiasis

- ID: D000014545

- Term: Urinary Calculi

- ID: D000052801

- Term: Male Urogenital Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10693

- Name: Kidney Calculi

- Relevance: HIGH

- As Found: Kidney Stone

- ID: M27126

- Name: Nephrolithiasis

- Relevance: HIGH

- As Found: Kidney Stone

- ID: M5399

- Name: Calculi

- Relevance: LOW

- As Found: Unknown

- ID: M22519

- Name: Pathological Conditions, Anatomical

- Relevance: LOW

- As Found: Unknown

- ID: M10698

- Name: Kidney Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17319

- Name: Urologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M27103

- Name: Urolithiasis

- Relevance: LOW

- As Found: Unknown

- ID: M17295

- Name: Urinary Calculi

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T4202

- Name: Oculocerebral Syndrome With Hypopigmentation

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000007669

- Term: Kidney Calculi

- ID: D000053040

- Term: Nephrolithiasis

### Misc Info Module

- Version Holder: 2024-05-31
