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

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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.

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Acknowledgments

We thank Prof. A. Renieri and F Mari (Genetica Medica, Università di Siena) for the genetic analysis.

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Authors and Affiliations

  1. Pediatric Nephrology and Dialysis Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via della Commenda 9, 20122, Milan, Italy

    Marisa Giani, Antonio Mastrangelo, Roberta Villa, Giuseppina Marra & Alberto Edefonti

  2. Laboratory of Clinical Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Stefano Turolo & Amedea Silvia Tirelli

  3. Institute of Pathology, University Hospital Basel, Basel, Switzerland

    Helmut Hopfer

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  1. Marisa Giani
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Correspondence to Antonio Mastrangelo.

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Giani, M., Mastrangelo, A., Villa, R. et al. Alport syndrome: the effects of spironolactone on proteinuria and urinary TGF-β1. Pediatr Nephrol 28, 1837–1842 (2013). https://doi.org/10.1007/s00467-013-2490-z

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  • DOI: https://doi.org/10.1007/s00467-013-2490-z

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