Fluid Balance, Hormones and Urine Proteomics in Nephrotic Syndrome in Childhood
Condition: Nephrotic Syndrome
MeSH terms: Nephrotic Syndrome; Nephrosis; Syndrome
Study type: Observational

Summary: 
      The purpose of this study is to describe the hormones controlling fluid balance in pediatric
      patients with nephrotic syndrome. Further more, an analysis of the urinary and plasma
      proteins will be done using proteomics. Different composition of proteins in the urine or
      plasma might indicate if the patients will respond to treatment or not.
    

Detailed description: 
      Nephrotic syndrome represents the association of proteinuria, hypoalbuminemia, oedema and
      hyperlipidemia. The pathogenesis of the oedemas remains controversial. The "underfill" theory
      is the traditional explanation where massive proteinuria leads to low plasma albumine and a
      subsequent decrease in intravascular osmotic pressure leading to edema formations. Because
      most patients are normotensive and have normal intravascular pressure the "overfill" theory
      has been proposed suggesting a primary defect in renal sodium handling being responsible for
      oedema formation.

      Ten percent of the children with nephrotic syndrome do not respond to standard steroid
      treatment and a significant proportion of these patients progress towards end-stage renal
      failure. At initial presentation it cannot be said if a patient will respond to treatment or
      not.

      The purposes of the sudy:

        1. To describe changes in the hormones, Aldosterone, Atrial Natriuretic Peptide (ANP),
           Arginin Vasopressin (AVP), Renin and Angiotensin II in patients with idiopathic
           nephrotic syndrome and to analyse to what extend the change in these hormones reflected
           a "underfill" or "overfill" situation.

        2. To describe changes in the urine concentration of the water channel AQP II and the
           sodium channel ENaC during the course of nephrotic syndrome.

        3. To test the hypothesis that urine and plasma proteomics from patients with steroid
           resistant nephrotic syndrome differs from patients with steroid sensitive nephrotic
           syndrome.

      50 pediatric patients with nephrotic syndrome will be included after informed consent from
      both parents.

      At day 1, 2, 3, 30 and 120 blood samples for hormones will be taken together with creatinin,
      albumine, Na+, K+, Hgb. An Echocardiography will be performed at day 1 and day 30 to
      determine v. cava inferior index.

      At day 1,30 and 120 urine and plasma will be collected for proteomics and measurement of AQP
      II and ENaC concentrations.

      Further more a clinical examination will be performed at day 1, 2, 3, 30 and 120 and weight,
      blood pressure and response to treatment will be recorded.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients with nephrotic syndrome will be included from 5 pediatric centrs in Denmark.
      
Biospecimen description: 
      Whole blood samples for hormone analyzes Urine samples for urine protomis, AQP II and ENaC
    
Keywords: Nephrotic syndrome; Underfill and overfill theory; Steroid resistance; Urine proteomics; AVP; ANP; Angiotensin II; Renin and Aldosterone