Ramipril lowers plasma FGF-23 in patients with diabetic nephropathy
Mahmut Ilker Yilmaz, Alper Sonmez, Mutlu Saglam, Yasemin Gulcan Kurt, Hilmi Umut Unal, Murat Karaman, Mahmut Gok, Hakki Cetinkaya, Tayfun Eyileten, Yusuf Oguz, Abdulgaffar Vural, Francesca Mallamaci, Carmine Zoccali, Mahmut Ilker Yilmaz, Alper Sonmez, Mutlu Saglam, Yasemin Gulcan Kurt, Hilmi Umut Unal, Murat Karaman, Mahmut Gok, Hakki Cetinkaya, Tayfun Eyileten, Yusuf Oguz, Abdulgaffar Vural, Francesca Mallamaci, Carmine Zoccali
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)).
Source: PubMed