Yilmaz Mahmut Ilker, Sonmez Alper, Saglam Mutlu, Kurt Yasemin Gulcan, Unal Hilmi Umut, Karaman Murat, Gok Mahmut, Cetinkaya Hakki, Eyileten Tayfun, Oguz Yusuf, Vural Abdulgaffar, Mallamaci Francesca, Zoccali Carmine
Department of Nephrology, Gulhane School of Medicine, Etlik-Ankara, Turkey.
Am J Nephrol. 2014;40(3):208-14. doi: 10.1159/000366169. Epub 2014 Oct 10.
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.
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).
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.
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)).
背景/目的：雷米普利可降低糖尿病性Zucker大鼠（伴进行性肾病）的肾成纤维细胞生长因子23（FGF-23）表达，改善蛋白尿，并使血清磷酸盐正常化，提示该药物的肾脏保护作用可能部分归因于血管紧张素转换酶（ACE）抑制作用降低FGF-23的效应。
在这项非随机研究中，我们测试了ACE抑制是否能降低1期慢性肾脏病（CKD）伴蛋白尿的2型糖尿病患者的循环FGF-23水平。在基线时以及使用雷米普利（n = 68）或氨氯地平（n = 32）治疗12周后，测量完整FGF-23、估算肾小球滤过率（eGFR）、蛋白尿以及内皮依赖性血流介导的（FMD）对缺血的反应和其他参数。
两组的血压下降幅度相似（p < 0.001）。然而，与氨氯地平治疗的患者相比，雷米普利治疗的患者24小时蛋白尿和FMD改善更明显（均p < 0.01）。雷米普利引起的蛋白尿变化（r = 0.47）和FMD变化（r = -0.49）与FGF-23的同时变化密切相关（p < 0.001），并且这种联系在多元回归分析中得到证实。在这些分析中，仅在排除FGF-23的模型中，FMD与蛋白尿变化之间的关系才具有统计学意义（p < 0.01），这表明内皮功能障碍和FGF-23共享一条导致肾损伤的共同途径。
本研究结果有助于提出以下假设：FGF-23可能与糖尿病肾病的蛋白尿和内皮功能障碍有关（clinicaltrials.gov（NCT01738945））。
