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

Marisa Giani, Antonio Mastrangelo, Roberta Villa, Stefano Turolo, Giuseppina Marra, Amedea Silvia Tirelli, Helmut Hopfer, Alberto Edefonti

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1837-1842
Number of pages6
JournalPediatric Nephrology
Issue number9
Publication statusPublished - Sep 2013


  • Aldosterone
  • Alport syndrome
  • Proteinuria
  • Renin-angiotensin system
  • Spironolactone
  • Urinary TGF-β1

ASJC Scopus subject areas

  • Nephrology
  • Pediatrics, Perinatology, and Child Health


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