Fluid Balance, Hormones and Urine Proteomics in Nephrotic Syndrome in Childhood

Nephrotic Syndrome

Nephrotic syndrome, Underfill and overfill theory, Steroid resistance, Urine proteomics, AVP, ANP, Angiotensin II, Renin and Aldosterone

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.

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.

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