Department of Pediatrics, Division of Pediatric Nephrology, University of Miami Miller School of Medicine, Miami, FL, USA.
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Pediatr Nephrol. 2021 Oct;36(10):3007-3022. doi: 10.1007/s00467-020-04843-6. Epub 2020 Nov 23.
Hypertension (HTN) and chronic kidney disease (CKD) are increasingly recognized in pediatric patients and represent risk factors for cardiovascular morbidity and mortality later in life. In CKD, enhanced tubular sodium reabsorption is a leading cause of HTN due to augmented extracellular fluid volume expansion. The renin-angiotensin-aldosterone system (RAAS) upregulates various tubular sodium cotransporters that are also targets of the hormone fibroblast growth factor 23 (FGF23) and its co-receptor Klotho. FGF23 inhibits the activation of 1,25-dihydroxyvitamin D that is a potent suppressor of renin biosynthesis. Here we review the complex interactions and disturbances of the FGF23-Klotho axis, vitamin D, and the RAAS relevant to blood pressure regulation and discuss the therapeutic strategies aimed at mitigating their pathophysiologic contributions to HTN.
高血压（HTN）和慢性肾脏病（CKD）在儿科患者中越来越受到重视，是成年后心血管发病率和死亡率的危险因素。在 CKD 中，由于细胞外液体积扩张，增强的肾小管钠重吸收是导致 HTN 的主要原因。肾素-血管紧张素-醛固酮系统（RAAS）上调了各种肾小管钠共转运蛋白，这些蛋白也是激素成纤维细胞生长因子 23（FGF23）及其共同受体 Klotho 的靶标。FGF23 抑制 1,25-二羟维生素 D 的激活，而 1,25-二羟维生素 D 是肾素生物合成的有效抑制剂。在这里，我们综述了 FGF23-Klotho 轴、维生素 D 和 RAAS 之间的复杂相互作用和紊乱，这些与血压调节有关，并讨论了旨在减轻它们对 HTN 的病理生理贡献的治疗策略。
