Objective
- To determine the therapeutic potential on the progression to renal failure of Angiotensin Converting Enzyme Inhibitors (ACE-I) in children and young adults with primary IgA Nephropathy.
- To detect the effect of this treatment on proteinuria and circulating IgA containing macromolecules
- To identify genetic, immunologic or histologic factors able to forecast responders and non responders .
IgA Nephropathy (IgAN) is one of the most common glomerulonephritis, accounting in Europe for 10-30% of all glomerular diseases that underwent renal biopsy. According to the 1994 EDTA Registry, 25% of patients with evolutive IgAN start renal replacement therapy by their twenties and other 35% by the age of 44 years. Considering the general progression rate of IgAN (25% of the cases need dialysis in 20 years),a successful treatment during the first two decades of life will provide the greatest potential benefits.
Clinical indicators of poor prognosis are proteinuria and hypertension. Angiotensin II (Ang II) plays an important role in systemic and glomerular hypertension, glomerular permselectivity and proteinuria as well as in modulating mesangial and tubular cell function. Many in vitro and clinical data indicate that ACE-I are the most promising agents for treatment of IgAN.
Based on these observations, this European multicenter study will investigate the potential benefits of ACE-I in young patients with IgAN presenting significant proteinuria.
Section 1: will deal with the clinical trial enrolling patients from 29 major European Centers of Pediatric Nephrology. Patients aged 20 years at time of renal biopsy (done<5 years before) showing prevalent IgA mesangial deposits, at high risk of progression (proteinuria 21 g/1.73m2/day) will be enrolled in a cohort large enough to achieve results of statistical significance (224 patients divided in treatment and placebo groups), in a follow-up sufficient to evaluate renal functional decline and eventual benefits(l-3 years). In the mean time the concertation with other Research Centers will reinforce this study by investigating the factors which are likely to influence the clinical response.
Section 2 will evaluate genetic factors modulating the response to ACE-I, studying the polymorphisms of several genes, including those coding for HLA, immunoglobulin switch regions, ACE and Ang II receptor (AT1), adducin and Na/H exchange pump.
Section 3 will focus on histology, providing new studies with confocal microscopy.
Section 4 is devoted to analyse the role of blood pressure, including continuous monitoring in selected cases. Finally in
Section 5 the role of immunologic factors peculiar for IgAN will be evaluated, including circulating macromolecular IgA, IgA immune complexes (IC), mixed IgA/IgG IC, IgA with altered glycosylation or abnormal electrical charge. Furthermore polymorphism of HLA class III genes (C4A,C4B,BF) and the relative phenotypes will be evaluated.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine nephrology
- natural sciences physical sciences optics microscopy confocal microscopy
- natural sciences biological sciences histology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Coordinator
10126 Torino
Italy
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