Neutrophil Extracellular Traps (NET's) in Prevalent Kidney Stone - Trial NCT06412822

Timeline & Enrollment

Primary Outcome

Neutrophil extracellular traps (NETs) excretion in 24h urine collection,Neutrophil extracellular traps (NETs) excretion in fasting urine,Neutrophil extracellular traps (NETs) excretion in 2e morning urine,Macrophages extracellular traps (MET's) excretion in 24h urine collection,Macrophages extracellular traps (MET's) excretion in fasting urine,Macrophages extracellular traps (MET's) excretion in 2e morning urine

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

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