Skrzypczyk Piotr, Wabik Anna Maria, Szyszka Michał, Józwiak Sergiusz, Bombiński Przemysław, Jakimów-Kostrzewa Aleksandra, Brzewski Michał, Pańczyk-Tomaszewska Małgorzata
Department of Pediatrics and Nephrology, Medical University of Warsaw, Warsaw, Poland.
Department of Pediatrics and Nephrology, Doctoral School, Medical University of Warsaw, Warsaw, Poland.
Front Pediatr. 2021 Nov 29;9:767394. doi: 10.3389/fped.2021.767394. eCollection 2021.
Experimental data indicate that activating mutations in the mTOR (mammalian target of rapamycin) pathway may lead to abnormal arterial wall structure. Vascular anomalies like arterial stenoses are reported in pediatric patients with tuberous sclerosis complex (TSC). In addition, large renal lesions (angiomyolipoma-AML and cysts) are risk factors for arterial hypertension in adult patients with TSC. This study aimed to assess blood pressure, including central blood pressure and arterial damage (early vascular aging-EVA) in children with TSC. In a group of 33 pediatric patients with TSC (11.13 ± 4.03 years, 15 boys, 18 girls), we evaluated peripheral and central office blood pressure, 24-h ambulatory blood pressure, and arterial damage: aortic pulse wave velocity (aPWV) [m/s], [score], augmentation index (AIx75HR [%]), common carotid artery intima-media thickness (cIMT) [mm], [score], stiffness of common carotid artery (E-tracking), renal lesions in magnetic resonance and ultrasonography, and selected biochemical parameters. The control group consisted of 33 healthy children (11.23 ± 3.28 years, 15 boys, 18 girls). In TSC group 7 (21.2%) children had arterial hypertension, 27 (81.8%) children had renal angiomyolipomas, 26 (78.8%)-renal cysts, and 4 (12.1%) patients were treated with mTOR inhibitors (2 patients with everolimus and 2 patients with sirolimus) at the moment of evaluation. Children with TSC had higher central systolic blood pressure (AoSBP) (98.63 ± 9.65 vs. 90.45 ± 6.87 [mm Hg], < 0.001), cIMT (0.42 ± 0.05 vs. 0.39 ± 0.03 [mm], = 0.011), cIMT score (0.81 ± 1.21 vs. 0.16 ± 0.57, = 0.007), aPWV (4.78 ± 0.81 vs. 4.25 ± 0.56 [m/s], = 0.003) and aPWV score (-0.14 ± 1.15 vs. -0.96 ± 0.87, = 0.002) compared to healthy children, without differences in AIx75HR (8.71 ± 15.90 vs. 5.24 ± 11.12 [%], = 0.319) and stiffness of common carotid artery. In children with TSC AoSBP correlated positively with serum cystatin C concentration ( = 0.377, = 0.030) and with maximum diameter of renal cyst ( = 0.419, = 0.033); mean arterial pressure (MAP) 24 h score correlated with serum cystatin C concentration ( = 0.433, = 0.013); and aPWV score with daily urinary albumin loss [mg/24 h] ( = 0.412, = 0.029). Children with tuberous sclerosis complex are at risk of elevated central blood pressure and early vascular aging. In children with TSC, blood pressure and arterial stiffness are related to renal involvement.
实验数据表明，mTOR（雷帕霉素哺乳动物靶点）信号通路中的激活突变可能导致动脉壁结构异常。据报道，患有结节性硬化症（TSC）的儿科患者存在诸如动脉狭窄等血管异常情况。此外，在成年TSC患者中，较大的肾脏病变（血管平滑肌脂肪瘤 - AML和囊肿）是动脉高血压的危险因素。本研究旨在评估TSC患儿的血压，包括中心血压和动脉损伤情况（早期血管老化 - EVA）。在一组33例TSC儿科患者（年龄11.13±4.03岁，15名男孩，18名女孩）中，我们评估了外周和中心诊室血压、24小时动态血压以及动脉损伤情况：主动脉脉搏波速度（aPWV）[米/秒]、[评分]、增强指数（AIx75HR [%]）、颈总动脉内膜中层厚度（cIMT）[毫米]、[评分]、颈总动脉硬度（E - 追踪）、磁共振成像和超声检查中的肾脏病变以及选定的生化参数。对照组由33名健康儿童（年龄11.23±3.28岁，15名男孩，18名女孩）组成。在TSC组中，7名（21.2%）儿童患有动脉高血压，27名（81.8%）儿童患有肾血管平滑肌脂肪瘤，26名（78.8%）患有肾囊肿，4名（12.1%）患者在评估时正在接受mTOR抑制剂治疗（2名使用依维莫司，2名使用西罗莫司）。与健康儿童相比，TSC患儿的中心收缩压（AoSBP）更高（98.63±9.65 vs. 90.45±6.87 [毫米汞柱]，<0.001）、cIMT更高（0.42±0.05 vs. 0.39±0.03 [毫米]，=0.011）、cIMT评分更高（0.81±1.21 vs. 0.16±0.57，=0.007）、aPWV更高（4.78±0.81 vs. 4.25±0.56 [米/秒]，=0.003）以及aPWV评分更高（ - 0.14±1.15 vs. - 0.96±0.87，=；0.002），而AIx75HR和颈总动脉硬度无差异（8.71±15.90 vs. 5.24±11.12 [%]，=0.3；19）。在TSC患儿中，AoSBP与血清胱抑素C浓度呈正相关（=0.377，=0.030），与肾囊肿最大直径呈正相关（=0.419，=0.033）；24小时平均动脉压（MAP）评分与血清胱抑素C浓度呈正相关（=0.433，=0.013）；aPWV评分与每日尿白蛋白丢失量[毫克/24小时]呈正相关（=0.412，=0.029）。患有结节性硬化症的儿童存在中心血压升高和早期血管老化的风险。在TSC患儿中，血压和动脉僵硬度与肾脏受累情况相关。
