Ramipril lowers plasma FGF-23 in patients with diabetic nephropathy

Am J Nephrol. 2014;40(3):208-14. doi: 10.1159/000366169. Epub 2014 Oct 10.

Abstract

Background/aims: 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.

Conclusion: 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)).

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Amlodipine / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Blood Pressure
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetic Nephropathies / blood*
  • Disease Progression
  • Endothelium, Vascular / pathology
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Follow-Up Studies
  • Humans
  • Ischemia / complications
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / complications
  • Male
  • Middle Aged
  • Phosphates / blood
  • Proteinuria / blood
  • Proteinuria / complications
  • Ramipril / therapeutic use*
  • Regression Analysis
  • Retrospective Studies

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • FGF23 protein, human
  • Phosphates
  • Amlodipine
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Ramipril

Associated data

  • ClinicalTrials.gov/NCT01738945