Neutrophil Extracellular Traps (NET's) in Prevalent Kidney Stone
- Conditions
- Kidney Stone
- Interventions
- Other: Blood samplingOther: Urine sampling
- Registration Number
- NCT06412822
- Lead Sponsor
- Brugmann University Hospital
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
- Patients with acute and/or chronic kidney disease, with stones or without stones, ambulatory or hospitalized in CHU Brugmann Brugmann.
- 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 & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description STONE group Blood sampling Adult subjects with kidney stones disease STONE group Urine sampling Adult subjects with kidney stones disease NON STONE group Urine sampling Control group: patients with acute and/or chronic kidney disease (CKD) without stones NON STONE group Blood sampling Control group: patients with acute and/or chronic kidney disease (CKD) without stones
- Primary Outcome Measures
Name Time Method Neutrophil extracellular traps (NETs) excretion in fasting urine 24 hours Assessment of NET excretion in fasting urine
Neutrophil extracellular traps (NETs) excretion in 24h urine collection 24 hours Assessment of NET excretion in 24h urine collection
Neutrophil extracellular traps (NETs) excretion in 2e morning urine 24 hours Assessment of NET excretion in 2e morning urine
Macrophages extracellular traps (MET's) excretion in 24h urine collection 24 hours Assessment of MET's in 24h urine collection
Macrophages extracellular traps (MET's) excretion in 2e morning urine 24 hours Assessment of MET's in 2e morning urine
Macrophages extracellular traps (MET's) excretion in fasting urine 24 hours Assessment of MET's in fasting urine
- Secondary Outcome Measures
Name Time Method Neutrophil extracellular traps (NETs) plasma levels 24 hours Neutrophil extracellular traps (NETs) plasma levels
Macrophages extracellular traps (MET's) plasma levels 24 hours Macrophages extracellular traps (MET's) plasma levels
Trial Locations
- Locations (1)
CHU Brugmann
🇧🇪Brussel, Belgium