Department of Cardiology, Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing, China.
Clinical Medical School, Beijing University of Chinese Medicine, Beijing, China.
Kidney Blood Press Res. 2021;46(2):236-244. doi: 10.1159/000515088. Epub 2021 Apr 1.
The underlying pathogenesis of patients with salt-sensitive hypertension expressing higher blood pressure and severer renal damage remains uncertain.
We recruited 329 subjects, 131 in salt-sensitive (SS) group, 148 in nonsalt-sensitive (NSS) group, and 50 healthy people in normal group and tested their renal function, 24-h ambulatory blood pressure, and growth factor series.
The SS group showed worse renal function with lower estimated glomerular filtration rate and higher urinary microalbumin, α-microglobulin, urinary protein Cr ratio, and urinary immunoglobulin. Most indicators in 24-h ambulatory blood pressure of the SS group were significantly enhanced than the NSS group, indicating their higher blood pressure. The significantly elevated growth factors in the SS group were AR, BMP-5, EG-VEGF, GH, HGF, IGFBP-2, IGFBP-3, IGFBP-6, MCSFR, NT-4, PDGF-AA, SCF, SCFR, VEGFR2, VEGFR3, and VEGF-D, compared to other 2 groups or one of them. PI3K-AKT pathway was activated in the SS group.
Differences in growth factors and pathways may account for the manifestations of the SS group. Activated PI3K-AKT pathway with higher IGFBP-3 and GH can lead to renal damage. Higher MCSFR in the SS group indicates that high blood pressure and severe kidney damage may be associated with the activation of the immune system. EG-VEGF, VEGFR2, VEGFR3, and VEGF-D can also explain the elevated blood pressure due to the dilated lymphatic system which drains excess sodium and water back into circulation. The SS group presented higher AR and HGF which may worsen renal function by regulating cell proliferation and tumor formation. However, due to the potential low awareness rate of hypertension at the very beginning, we cannot ensure the exact occurrence order of blood pressure, renal damage, and salt sensitivity. Therefore, further studies which can track data from the onset of hypertension are needed.
盐敏感型高血压患者血压升高幅度更大、肾脏损害更严重，但具体的发病机制尚不清楚。
共纳入 329 例受试者，其中盐敏感组 131 例，非盐敏感组 148 例，正常组 50 例。检测所有受试者的肾功能、24 小时动态血压和生长因子谱。
盐敏感组的肾功能更差，肾小球滤过率估计值更低，尿微量白蛋白、α-微球蛋白、尿蛋白肌酐比和尿免疫球蛋白更高。盐敏感组的 24 小时动态血压多项指标均显著高于非盐敏感组，提示血压更高。盐敏感组的生长因子显著升高，包括 AR、BMP-5、EG-VEGF、GH、HGF、IGFBP-2、IGFBP-3、IGFBP-6、MCSFR、NT-4、PDGF-AA、SCF、SCFR、VEGFR2、VEGFR3 和 VEGF-D，与其他两组或其中一组相比均有显著差异。盐敏感组的 PI3K-AKT 通路被激活。
生长因子和通路的差异可能是盐敏感组表现不同的原因。PI3K-AKT 通路的激活导致 IGFBP-3 和 GH 升高，进而导致肾脏损伤。盐敏感组中较高的 MCSFR 表明，高血压和严重的肾脏损害可能与免疫系统的激活有关。EG-VEGF、VEGFR2、VEGFR3 和 VEGF-D 也可以解释由于淋巴系统扩张导致的血压升高，该系统将过多的钠和水排回循环。盐敏感组中较高的 AR 和 HGF 可能通过调节细胞增殖和肿瘤形成而使肾功能恶化。然而，由于高血压最初的知晓率可能较低，我们不能确定血压、肾脏损害和盐敏感性的确切发生顺序。因此，需要进一步的研究来跟踪高血压发病的数据。
