title: Ramipril lowers plasma FGF-23 in patients with diabetic nephropathy.
abstract: OBJECTIVE
  Ramipril attenuates renal Fibroblast growth factor-23 (FGF-23) expression, ameliorates proteinuria and normalizes serum phosphate in the diabetic Zucker rat with progressive renal disease suggesting that the renoprotective effect by this drug may be in part due to a FGF-23-lowering effect of angiotensin-converting enzyme (ACE) inhibition.
  
  
  METHODS
  In this nonrandomized study, we tested whether ACE-inhibition reduces circulating FGF-23 in type-2 diabetics with stage-1 chronic kidney disease (CKD) and proteinuria. Intact FGF-23, the eGFR, proteinuria and the endothelium-dependent flow-mediated (FMD) response to ischemia and other parameters were measured at baseline and after 12-weeks of treatment with ramipril (n = 68) or amlodipine (n = 32).
  
  
  RESULTS
  Blood Pressure (BP) fell to a similar extent (p < 0.001) in the two groups. However, 24 h proteinuria and the FMD improved more (both p < 0.01) in ramipril-treated patients than in amlodipine-treated patients. Changes in proteinuria (r = 0.47) and in FMD (r = -0.49) by ramipril were closely associated (p < 0.001) with simultaneous changes in FGF-23 and this link was confirmed in multiple regression analyses. In these analyses, the relationship between FMD and proteinuria changes attained statistical significance (p < 0.01) only in a model excluding FGF-23 suggesting that endothelial dysfunction and FGF-23 share a common pathway conducive to renal damage.
  
  
  CONCLUSIONS
  Findings in this study contribute to generate the hypothesis that FGF-23 may be implicated in proteinuria and in endothelial dysfunction in diabetic nephropathy (clinicaltrials.gov (NCT01738945)).
authors.affiliation: Department of Nephrology, Gulhane School of Medicine, Etlik-Ankara, Turkey.
authors.forename: Mahmut Ilker
authors.initials: MI
authors.lastname: Yilmaz
authors.forename: Alper
authors.initials: A
authors.lastname: Sonmez
authors.forename: Mutlu
authors.initials: M
authors.lastname: Saglam
authors.forename: Yasemin Gulcan
authors.initials: YG
authors.lastname: Kurt
authors.forename: Hilmi Umut
authors.initials: HU
authors.lastname: Unal
authors.forename: Murat
authors.initials: M
authors.lastname: Karaman
authors.forename: Mahmut
authors.initials: M
authors.lastname: Gok
authors.forename: Hakki
authors.initials: H
authors.lastname: Cetinkaya
authors.forename: Tayfun
authors.initials: T
authors.lastname: Eyileten
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Oguz
authors.forename: Abdulgaffar
authors.initials: A
authors.lastname: Vural
authors.forename: Francesca
authors.initials: F
authors.lastname: Mallamaci
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
mesh_terms: D000328:Adult; D017311:Amlodipine / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D003928:Diabetic Nephropathies / Q000097:blood*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005500:Follow-Up Studies; D006801:Humans; D007511:Ischemia / Q000150:complications; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000097:blood; D011507:Proteinuria / Q000097:blood / Q000150:complications; D017257:Ramipril / Q000627:therapeutic use*; D012044:Regression Analysis; D012189:Retrospective Studies
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; C000717427:FGF23 protein, human; D010710:Phosphates; D017311:Amlodipine; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D017257:Ramipril