Validation of Biomarkers of Diabetic Nephropathy in Type I Diabetic Children
Condition: Type 1 Diabetes Mellitus With Diabetic Nephropathy
MeSH terms: Kidney Diseases; Diabetic Nephropathies; Diabetes Mellitus, Type 1
Study type: Observational

Summary: 
      About 30 to 40% of patients suffering from type I diabetes are at risk of developing a
      diabetic nephropathy (DN) leading more or less rapidly to an end-stage renal disease.
      Nowadays, the microalbuminuria is the most often used clinical parameter for possible onset
      of DN. However, it is a late (because it permits to detect a renal disease already present),
      non-specific and low sensitive biomarker.

      Therefore the main objective of this study is to identify early urinary biomarkers predictive
      of DN in children with type I diabetes, before the appearance of a microalbuminuria.
    

Detailed description: 
      Once the type I diabetes is diagnosed, the speed of progression to a DN is very variable.
      Thus, the discovery of biomarkers able to distinguish progressor patients from non-progressor
      since the appearance of a microalbuminuria, is crucial in order to take care of progressor
      patients the earlier and to slow down the disease progression.

      The investigators have shown that urine is a biological sample extremely well suited for
      proteome analysis with the aim to identify biomarkers of renal damages. Indeed, they were the
      first to analyze the urinary proteome of infant using capillary electrophoresis-coupled mass
      spectrometry. This technic permits to analyse the entire urinary proteome of a person in one
      hour.

      Several laboratories tried to identify other predictive urinary biomarkers of the development
      of a DN in diabetic patients, but with limited success and nowadays in the clinical practice
      they still use the measure of the microalbuminuria. Contrary to precedent studies, the
      investigators develop an analysis without a priori and starting with early samples (without
      any signs of DN) associating the urinary peptide profile with the DN progression over 9-10
      years.

      This is a nested case-control study in a cohort of 317 patients constituting the urinary
      biological collection. (The urinary samples of a type I diabetic cohort of 317 patients seen
      between 2004 and 2008 have been collected.) These patients will be contacted at the end of
      2012 to obtain a number of participation of 180 patients authorizing the use aposteriori of
      their urinary samples. Among this cohort, the investigators evaluate at 90 the number of
      patients with a DN defined by a dosage of microalbuminuria higher than 100 mg/L.

      The primary endpoint of this study is therefore the identification of urinary biomarkers
      predictive of DN in type I diabetes pediatric patients.

      The secondary endpoints are :

        -  The estimation of sensibility and specificity parameters, and the Area Under the Curve
           (AUC).

        -  The identification of factors associated with the variability of biomarkers expression
           such as the age at the moment of the diagnosis, the time between the diagnosis and the
           urinary collection, the rate of microalbuminuria, and the type of insulin used by the
           patient.

        -  And in the subgroup of patients for whom two urinary samples have been collected, the
           investigators want to study the urinary proteome stability in patients with no DN in
           2013.
    

Intervention name(s): Urinary sample collection
Intervention type(s): Other
Intervention description(s): urinary sample collection will be done at the inclusion visit for the assessment of the microalbuminuria ( < or > than 100mg/L)
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients are selected in a cohort of 317 type I diabetic children constituting a urine
        samples collection. Indeed, urine sample of 317 patients have been collected between 2004
        and 2008. These patients will be called to obtain the participation of 180 children in this
        study.
      
Biospecimen description: 
      Urine
    
Keywords: Microalbuminuria; diabetic nephropathy; type I diabetes; early predictive urinary biomarkers