Document Detail


Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations.
MedLine Citation:
PMID:  20191369     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Wilms' tumor suppressor gene 1 (WT1) encodes a transcription factor involved in kidney and gonadal development. WT1 is also a key regulator of podocyte functions and mutations have been found in a small percentage of children with isolated or syndromal steroid-resistant nephrotic syndrome. It is commonly assumed that the nephrotic syndrome (NS) in patients with WT1 mutations is unresponsive to therapy and characterized by rapid progression to end-stage renal disease. We report long-term observations in 3 children with focal-segmental glomerulosclerosis associated with WT1 mutations and NS (2 cases) or nephrotic range proteinuria (1 case). All patients showed a favorable response to an intensified therapy consisting of cyclosporin A (CyA) in combination with induction therapy with intravenous and oral prednisone. Treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was added to the regimen at various times. As shown both by the short-term response and during long-term follow-up, this treatment resulted in clinical remission of the NS and/or significant reduction of proteinuria, while normal renal function could be maintained over many years. Thus, glomerular diseases in selected patients with mutations in genes regulating renal development and podocyte function may respond to combination therapy with CyA and corticosteroids.
Authors:
Jutta Gellermann; Constantinos J Stefanidis; Andromachi Mitsioni; Uwe Querfeld
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Publication Detail:
Type:  Case Reports; Journal Article     Date:  2010-02-27
Journal Detail:
Title:  Pediatric nephrology (Berlin, Germany)     Volume:  25     ISSN:  1432-198X     ISO Abbreviation:  Pediatr. Nephrol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-05-21     Completed Date:  2010-08-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8708728     Medline TA:  Pediatr Nephrol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1285-9     Citation Subset:  IM    
Affiliation:
Department of Pediatric Nephrology, Charité Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. jutta.gellermann@charite.de
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Adolescent
Angiotensin II Type 1 Receptor Blockers / therapeutic use
Angiotensin-Converting Enzyme Inhibitors / therapeutic use
Child
Cyclosporine / therapeutic use*
Drug Resistance
Drug Therapy, Combination
Female
Glomerulosclerosis, Focal Segmental / drug therapy*,  genetics
Humans
Injections, Intravenous
Male
Mutation*
Nephrotic Syndrome / drug therapy*,  genetics,  metabolism
Prednisone / therapeutic use*
Proteinuria / drug therapy,  genetics
Treatment Outcome
WT1 Proteins / genetics*,  metabolism
Chemical
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Angiotensin-Converting Enzyme Inhibitors; 0/WT1 Proteins; 53-03-2/Prednisone; 59865-13-3/Cyclosporine
Comments/Corrections
Comment In:
Pediatr Nephrol. 2010 Jul;25(7):1197-9   [PMID:  20195644 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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