Ignite Creation Date:
2024-05-19 @ 5:34 PM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06412822
Status:
RECRUITING
Last Update Posted:
2024-05-14
First Post:
2024-05-07
Brief Title:
Neutrophil Extracellular Traps NETs in Prevalent Kidney Stone
Sponsor:
Brugmann University Hospital
Organization:
Brugmann University Hospital
Study Overview
Official Title:
Neutrophil Extracellular Traps NETs in Prevalent Kidney Stone Cross-section Non-drug Clinical Study-Analysis of Biological Fluids Residual Human Body Material RHBM STONETs Project
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 METs 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 NETs or METs 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 NETMETs excretion in the urine as a non-invasive method of NETMETosis 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 NETMETs concentrations in the urine with those in plasma
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 METs 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 NETs or METs 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 NETMETs excretion in the urine as a non-invasive method of NETMETosis 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 NETMETs concentrations in the urine with those in plasma
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None