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Alport syndrome: the effects of spironolactone on proteinuria and urinary TGF-β1.
- Source :
-
Pediatric nephrology (Berlin, Germany) [Pediatr Nephrol] 2013 Sep; Vol. 28 (9), pp. 1837-42. Date of Electronic Publication: 2013 Jun 11. - Publication Year :
- 2013
-
Abstract
- Background: Alport syndrome (AS) is a progressive hereditary glomerular disease. Recent data indicate that aldosterone promotes fibrosis mediated by the transforming growth factor-β1 (TGF-β1) pathway, which may worsen proteinuria. Spironolactone (SP) antagonizes aldosterone and this study aimed to evaluate the efficacy of SP in reducing proteinuria and urinary TGF-β1 excretion in proteinuric AS patients.<br />Methods: The study involved ten children with AS, normal renal function, and persistent proteinuria (>6 months; uPr/uCr ratio >1). SP 25 mg once a day for 6 months was added to existing ACE inhibitor treatment with or without angiotensin-II receptor blockade. Urine and blood samples were examined monthly. Urinary TGF-β1 levels were measured twice before and three times during SP treatment. Plasma renin activity (PRA) and serum aldosterone levels were also measured. In eight patients, uProt/uCreat was also assessed after 9 months and 12 months of SP treatment.<br />Results: After beginning SP therapy, all patients showed significant decrease in mean uProt/uCreat ratio (1.77 ± 0.8 to 0.86 ± 0.6; p < 0.001) and mean urinary TGF-β1 levels (104 ± 54 to 41 ± 20 pg/mgCreatinine; p < 0.01), beginning after 30 days of treatment and remaining stable throughout SP administration. PRA remain unchanged, and mean serum aldosterone increased from 105 ± 72 pg/ml to 303 ± 156 pg/ml (p < 0.001). The only side effect was gynecomastia in an obese boy. After 1 year of therapy, mean uProt/uCreat remains low (0.82 ± 0.48).<br />Conclusions: Addition of SP to ACE-I treatment with or without angiotensin II receptor blokers (ARB) significantly reduced proteinuria. This was mediated by decreased urinary TGF-β1 levels and not associated with major side effects.
- Subjects :
- Adolescent
Aldosterone blood
Angiotensin-Converting Enzyme Inhibitors therapeutic use
Blood Pressure physiology
Child
Creatinine urine
Enalapril therapeutic use
Female
Humans
Kidney Function Tests
Male
Mutation physiology
Nephritis, Hereditary genetics
Proteinuria urine
Treatment Outcome
Young Adult
Mineralocorticoid Receptor Antagonists therapeutic use
Nephritis, Hereditary drug therapy
Nephritis, Hereditary urine
Proteinuria drug therapy
Spironolactone therapeutic use
Transforming Growth Factor beta1 urine
Subjects
Details
- Language :
- English
- ISSN :
- 1432-198X
- Volume :
- 28
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Pediatric nephrology (Berlin, Germany)
- Publication Type :
- Academic Journal
- Accession number :
- 23748277
- Full Text :
- https://doi.org/10.1007/s00467-013-2490-z