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Molecular Prediction of Development, Progression or Complications of Kidney, Immune or Transplantation-related Diseases

Recruiting
Conditions
Metabolic Disease
Chronic Kidney Diseases
Solid-organ Transplantation
Cancer
Acute Kidney Injury
Immune Diseases
Registration Number
NCT05318196
Lead Sponsor
University Hospital, Toulouse
Brief Summary

Managing patients with renal failure requires an understanding of the molecular mechanisms that lead to its occurrence (i.e. upstream of the disease), its worsening and its persistence (i.e. downstream), while also specifying the risk of worsening renal failure (risk stratification, intolerance to the treatment or complications (infectious, metabolic, cardiovascular, cancer...). Nephrogene 2.0 aims to study these different components of kidney, immune and solid organ transplantation (SOT)-related diseases.

Detailed Description

Acute renal failure (ARF) and chronic kidney disease (CKD) are frequent pathologies (850 million people are affected worldwide). Renal failure is associated with an increased morbidity and mortality, including an increased risk of infections, drug toxicity and cardiovascular death. The causes of renal failure are numerous: metabolic (diabetes, hypertension), immunological (autoimmune diseases, monoclonal gammopathies), toxic (environment, drugs), genetic, infectious, ischemic, paraneoplastic... Any episode of ARF is also accompanied by a risk of secondary CKD (relative risk multiplied by 9).

The mechanisms leading to renal failure are multiple and combine predisposing genetic factors, inadequate intra-renal or systemic immune response, endothelial and epithelial dysfunctions, and potentially inappropriate regenerative capacity. In addition, renal failure or its treatment itself may be accompanied by additional renal lesions (e.g. nephrotoxicity of calcineurin inhibitors used as anti-rejection treatment in transplantation, hemodynamic intolerance with secondary ARF during hemodialysis sessions, iatrogenic ARF when using diuretics or inhibitors of the renin angiotensin system) or extra-renal complications (e.g. immunosuppression and infections induced by immunomodulatory therapies during autoimmune diseases or for prevention of transplant rejection; vascular diseases secondary to phosphocalcic disorders).

Patients included in the NEPHROGENE 2.0 cohort will be followed during 10 years and clinical data and biological samples will be collected at the inclusion in the cohort, at each monitoring programmed in their usual care and and at each event (infection, acute kidney injury, cancer...). Samples will be collected according to the symptoms of the patients.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
5000
Inclusion Criteria
  • Patients (> 18 year of age) with kidney disease or at risk to develop a kidney disease,
  • Patients followed by a practitioner of the Department of Nephrology and Organ Transplantations of the University Hospital of Toulouse (France)
Exclusion Criteria
  • consent deny
  • inability of the patient or its family to give consent.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Identification of the molecular mechanisms underlying kidney, immune and solid organ transplantation-related diseases.yearly and up to 10 years after inclusion in the study

To identify the molecular mechanisms underlying kidney, immune and solid organ transplantation-related diseases. An unbiased multi-omic approach (including peptidomics, metabolomics, genome sequencing, and flow cytometry and transcriptomic of circulating immune cells) will be performed at the inclusion in the study and correlated to specific end-points (acute kidney injury, kidney failure progression, end-stage kidney disease, infection, cancer according to the underlying condition). Multiple measurements will be studied individually to identify genes variations, gene expression changes, urinary or plasma peptides abundance, immune cells relative abundance in the blood that correlate with the end-point. In a second step, an attempt to combine them in a single predictive signature using artificial intelligence approach.

Secondary Outcome Measures
NameTimeMethod
Identification of the predictive factors (immunological, metabolic, genetic…) for the development or progression of renal diseasesup to 10 years after inclusion in the study

To identify the predictive factors (immunological, metabolic, genetic...) for the development or progression of renal diseases: end-points will be end-stage kidney disease, or a decrease of the estimated glomerular filtration rate (eGFR) \> 50%

To specify the individual risk of complications secondary to SOT or its treatmentup to 10 years after inclusion in the study

To specify the individual risk of renal and immunological complications secondary to cancer or hematological malignancies, or their treatments: end points will be the development of acute kidney injury, end-stage kidney disease or \>50% reduction of the eGFR

Identification of the molecular mechanisms (immunological, genetic…) driving complications of kidney, immune and SOT-related diseasesup to 10 years after inclusion in the study

To identify the molecular mechanisms (immunological, genetic...) driving complications of kidney, immune and SOT-related diseases: end-points will the development of bacterial, viral (CytoMégaloVirus, Herpes simplex virus, varicella-zoster virus, BK virus...) or fungal (candidiasis, aspergillosis...) infections, as well as cardiovascular events or other complications

Trial Locations

Locations (1)

Rangueil University Hospital

🇫🇷

Toulouse, France

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