title: 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.affiliation: Pediatric Nephrology and Dialysis Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda 9, 20122, Milan, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Giani
authors.forename: Antonio
authors.initials: A
authors.lastname: Mastrangelo
authors.forename: Roberta
authors.initials: R
authors.lastname: Villa
authors.forename: Stefano
authors.initials: S
authors.lastname: Turolo
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Marra
authors.forename: Amedea Silvia
authors.initials: AS
authors.lastname: Tirelli
authors.forename: Helmut
authors.initials: H
authors.lastname: Hopfer
authors.forename: Alberto
authors.initials: A
authors.lastname: Edefonti
mesh_terms: D000293:Adolescent; D000450:Aldosterone / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology; D002648:Child; D003404:Creatinine / Q000652:urine; D004656:Enalapril / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009154:Mutation / Q000502:physiology; D009394:Nephritis, Hereditary / Q000188:drug therapy* / Q000235:genetics / Q000652:urine*; D011507:Proteinuria / Q000188:drug therapy* / Q000652:urine; D013148:Spironolactone / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000652:urine*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D053773:Transforming Growth Factor beta1; D013148:Spironolactone; D000450:Aldosterone; D004656:Enalapril; D003404:Creatinine