Milovanova L Iu, Milovanov Iu S, Kozlovskaia L V, Mukhin N A
Ter Arkh. 2013;85(6):17-24.
To study the clinical significance of determining the serum concentration of phosphorus and calcium metabolism regulators--the morphogenetic proteins FGF-23 and Klotho in patients with different stages of chronic kidney disease (CKD).
The serum levels of FGF-23 (a human FGF-23 ELISA kit with full-length anti-FCF-23 monoclonal antibodies) and Klotho (a human alpha-K1 ELISA with anti-Klotno antibodies) were investigated in 70 patients with Stages I--VD CKD (41 patients with chronic glomerulonephritis, including 10 with nephritis in systemic diseases, 22 with tubulointerstitial nephritis, and 7 with hypertensive nephroslerosis). The morphogenetic proteins were studied by the specialists of the LiTECH diagnostic laboratory according to the standard protocol.
As CKD progressed from Stage I to VD, there were increased FGF-23 concentrations and decreased Klotho levels in the examinees' serum. The highest FGF-23 level and low Klotho concentration were noted in the group of patients on regular hemodialysis treatment (Stage VD). There was a strong inverse correlation between Klotho levels and proteinuria, C-reactive protein, and protein-energy insufficiency, which suggests that these factors influence the serum level of Klotho. The serum levels of FGF-23 and intact parathyroid hormone correlated with these values to a lesser degree. Analysis of the content of the morphogenetic proteins in patients with anemia versus those with CKD of the same stages and target hemoglobin values revealed low Klotho concentrations and high FGF-23 levels (r = 0.602; p < 0.01 and r = -0.450; p < 0.01, respectively). Forty-nine hypertensive patients showed a direct strong relationship between elevated serum FGF-23 levels and an inverse strong one between the reduced serum Klotho levels and the increased posterior left ventricular wall (r = 0.552; p < 0.01 and r = -0,587; p < 0.01, respectively). The same strong association was found between the higher serum level of FCF-23 (r = 0.492; p < 0.01) and the concentration of Klotho (r = -0.537; p < 0.01) and peripheral vascular resistance index (as evidenced by Doppler ultrasound study).
Along with the active participation of the morphogenetic proteins (FGF-23 and Klotho) in mineral metabolism and its disturbances in CKD, their role is apparent in the development of cardiovascular events (in particular, through the involvement in the processes of vascular calcification and cardiac remodeling), anemia (through the possible effect on iron metabolism, enhanced ischemia of renal interstitial tissue with impaired Klotho production), and protein-energy insufficiency (through the participation in the processes of inflammation, oxidative stress, and protein synthesis).
研究测定慢性肾脏病（CKD）不同阶段患者血清中磷和钙代谢调节因子——形态发生蛋白FGF - 23和Klotho的临床意义。
对70例I - VD期CKD患者（41例慢性肾小球肾炎患者，其中10例为系统性疾病相关性肾炎，22例为肾小管间质性肾炎，7例为高血压性肾硬化）的血清FGF - 23水平（采用含全长抗FGF - 23单克隆抗体的人FGF - 23 ELISA试剂盒）和Klotho水平（采用含抗Klotho抗体的人α - Kl ELISA法）进行检测。LiTECH诊断实验室的专业人员按照标准方案对形态发生蛋白进行研究。
随着CKD从I期进展至VD期，受检者血清中FGF - 23浓度升高，Klotho水平降低。规律血液透析治疗组（VD期）患者的FGF - 23水平最高，Klotho浓度最低。Klotho水平与蛋白尿、C反应蛋白及蛋白质 - 能量不足之间存在强烈的负相关，提示这些因素影响血清Klotho水平。FGF - 23和完整甲状旁腺激素的血清水平与这些指标的相关性较弱。对贫血患者与相同阶段且目标血红蛋白值相同的CKD患者的形态发生蛋白含量分析显示，Klotho浓度较低，FGF - 23水平较高（r分别为0.602；p < 0.01和r = - 0.450；p < 0.01）。49例高血压患者血清FGF - 23水平升高与血清Klotho水平降低及左心室后壁增厚之间存在直接的强相关性（r分别为0.552；p < 0.01和r = - 0.587；p < 0.01）。血清FGF - 23水平升高（r = 0.492；p < 0.01）及Klotho浓度（r = - 0.537；p < 0.01）与外周血管阻力指数之间也存在同样的强相关性（经多普勒超声研究证实）。
形态发生蛋白（FGF - 23和Klotho）不仅积极参与矿物质代谢及其在CKD中的紊乱过程，它们在心血管事件（特别是通过参与血管钙化和心脏重塑过程）、贫血（可能通过影响铁代谢，增强肾间质组织缺血并损害Klotho生成）及蛋白质 - 能量不足（通过参与炎症、氧化应激和蛋白质合成过程）的发生发展中也具有明显作用。
