Alport syndrome: the effects of spironolactone on proteinuria and urinary TGF-β1.

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.

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.

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).

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.

• Authors: Marisa Giani, Antonio Mastrangelo, Roberta Villa, Stefano Turolo, Giuseppina Marra, Amedea Silvia Tirelli, Helmut Hopfer, Alberto Edefonti
• Journal: Pediatric nephrology (Berlin, Germany) (Pediatr Nephrol) Vol. 28 Issue 9 Pg. 1837-42 (Sep 2013) ISSN: 1432-198X [Electronic] Germany
• PMID: 23748277 (Publication Type: Journal Article)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Mineralocorticoid Receptor Antagonists
• Transforming Growth Factor beta1
• Spironolactone
• Aldosterone
• Enalapril
• Creatinine

Topics

• Adolescent
• Aldosterone (blood)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Blood Pressure (physiology)
• Child
• Creatinine (urine)
• Enalapril (therapeutic use)
• Female
• Humans
• Kidney Function Tests
• Male
• Mineralocorticoid Receptor Antagonists (therapeutic use)
• Mutation (physiology)
• Nephritis, Hereditary (drug therapy, genetics, urine)
• Proteinuria (drug therapy, urine)
• Spironolactone (therapeutic use)
• Transforming Growth Factor beta1 (urine)
• Treatment Outcome
• Young Adult