Pediatric Nephrology

, Volume 28, Issue 9, pp 1837–1842

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
Original Article

DOI: 10.1007/s00467-013-2490-z

Cite this article as:
Giani, M., Mastrangelo, A., Villa, R. et al. Pediatr Nephrol (2013) 28: 1837. doi:10.1007/s00467-013-2490-z

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.

Keywords

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

Copyright information

© IPNA 2013

Authors and Affiliations

  • Marisa Giani
    • 1
  • Antonio Mastrangelo
    • 1
  • Roberta Villa
    • 1
  • Stefano Turolo
    • 2
  • Giuseppina Marra
    • 1
  • Amedea Silvia Tirelli
    • 2
  • Helmut Hopfer
    • 3
  • Alberto Edefonti
    • 1
  1. 1.Pediatric Nephrology and Dialysis UnitFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
  2. 2.Laboratory of Clinical PathologyFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
  3. 3.Institute of PathologyUniversity Hospital BaselBaselSwitzerland

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