慢性肾脏病患者中由于成纤维细胞生长因子-23（FGF-23）/α-klotho失衡导致的心血管重塑
Cardiovascular remodeling as a result of fibroblast growth factor-23 (FGF-23)/Klotho imbalance in patients with CKD.
作者信息
Milovanova Ludmila Yu, Taranova Marina V, Milovanova Svetlana Yu, Kozlovskaya Lysenko Lidia V, Pasechnik Anastasia I, Kozlov Vasiliy V, Beketov Vladimir D, Volkov Alexey V, Ratanov Mikhail
机构信息
Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8, Bld. 2, 119991, Moscow, Russian Federation.
Clinic of Nephrology and Internal Diseases, Rossolimo Str. 11, Bld. 5, 119992, Moscow, Russian Federation.
出版信息
Int Urol Nephrol. 2022 Jul;54(7):1613-1621. doi: 10.1007/s11255-021-03046-8. Epub 2021 Oct 30.
BACKGROUND
In chronic kidney disease (CKD) cardiovascular remodeling (CVR) is very frequent compared with general population and, as suppose, may be associated with «new» renal risk factors. The aim of study was to estimate association of new serum biomarkers (FGF-23, Klotho) and traditional biomarker of cardiac damage-serum Troponin I (sTr-I) with signs of CVR.
METHODS
One hundred thirty CKD G1-5D patients without cardiovascular disease (CVD) clinical manifestation were included. We measured serum FGF-23, Klotho and sTr-I. The instrumental methods were: echocardiography, SphygmoCor test [Pulse Wave Velocity (PWV), Central (aortic) Blood Pressure (CBP), Subendocardial Blood Supply (SBS)].
RESULTS
FGF-23 level correlated with: sTr-I (r = 0.512; p < 0.01), eccentric left ventricular hypertrophy, LVH (r = 0.543; p < 0.01), SBS (r = - 0.499; p < 0.05). There were no differences of FGF-23 level in patients with normal and high CBP. Klotho correlated with concentric LVH (r = - 0.451; p < 0.01), PWV (r = - 0.667; p < 0.001), Cardiac Calcification Score, CCS (r = - 0.581; p < 0.01). Multivariate analysis revealed positive independent association of FGF-23 with eccentric LVH (OR = 1.036, 95% CI (1.004-1.068); p = 0.038). Klotho was a negative determinant for concentric LVH (OR = 0.990, 95% CI 0.987-0.994; p < 0.001), increased PWV (OR = 0.984, 95% CI (0.977-0.991); p < 0.001) and CCS (OR = 0.991, 95% CI (0.988-0.995); p < 0.001). In addition, multivariate analysis revealed a relationship between serum Klotho (OR = 0.980, 95% CI (0.964-0.996); p = 0.016), FGF-23 (OR = 3.145, 95% CI (1.020-9.695); p = 0.046) and troponin I level.
CONCLUSION
In CKD patients without CVD clinical manifestation increased serum FGF-23 level and decreased Klotho are associated with CVR: FGF-23 with eccentric LVH (independently of CBP), Klotho determinate concentric LVH, PWV and CCS. Moderately elevated sTr-I levels may be a manifestation of FGF-23/Klotho imbalance in CKD.
背景
与普通人群相比，慢性肾脏病（CKD）患者中心血管重塑（CVR）非常常见，并且，可以推测，其可能与“新的”肾脏危险因素相关。本研究的目的是评估新型血清生物标志物（FGF-23、Klotho）以及心脏损伤的传统生物标志物——血清肌钙蛋白I（sTr-I）与CVR体征之间的关联。
方法
纳入130例无心血管疾病（CVD）临床表现的CKD G1-5D患者。我们检测了血清FGF-23、Klotho和sTr-I。使用的仪器检查方法包括：超声心动图、SphygmoCor检测[脉搏波速度（PWV）、中心（主动脉）血压（CBP）、心内膜下血供（SBS）]。
结果
FGF-23水平与以下指标相关：sTr-I（r = 0.512；p < 0.01）、离心性左心室肥厚（LVH）（r = 0.543；p < 0.01）、SBS（r = -0.499；p < 0.05）。CBP正常和升高的患者中FGF-23水平无差异。Klotho与向心性LVH（r = -0.451；p < 0.01）、PWV（r = -0.667；p < 0.001）、心脏钙化评分（CCS）（r = -0.581；p < 0.01）相关。多因素分析显示FGF-23与离心性LVH呈正独立关联（OR = 1.036，95%可信区间（1.004 - 1.068）；p = 0.038）。Klotho是向心性LVH（OR = 0.990，95%可信区间0.987 - 0.994；p < 0.001）、PWV升高（OR = 0.984，95%可信区间（0.977 - 0.991）；p < 0.001）和CCS（OR = 0.991，95%可信区间（0.988 - 0.995）；p < 0.001）的负性决定因素。此外，多因素分析显示血清Klotho（OR = 0.980，95%可信区间（0.964 - 0.996）；p = 0.016）、FGF-23（OR = 3.145，95%可信区间（1.020 - 9.695）；p = 0.046）与肌钙蛋白I水平之间存在关联。
结论
在无CVD临床表现的CKD患者中，血清FGF-23水平升高和Klotho降低与CVR相关：FGF-23与离心性LVH相关（独立于CBP），Klotho决定向心性LVH、PWV和CCS。sTr-I水平中度升高可能是CKD中FGF-23/Klotho失衡的一种表现。
Zotero 插件