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常染色体显性遗传多囊肾病的心血管风险早期标志物。

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease.

机构信息

Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.

Nephrology and Dialysis Unit, Hospital ICOT Latina, Sapienza University of Rome, Rome, Italy.

出版信息

Kidney Blood Press Res. 2017;42(6):1290-1302. doi: 10.1159/000486011. Epub 2017 Dec 15.

Abstract

BACKGROUND/AIMS: Cardiovascular disease is the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients, often before the onset of renal failure, and the pathogenetic mechanism is not yet well elucidated. The aim of the study was to identify early and noninvasive markers of cardiovascular risk in young ADPKD patients, in the early stages of disease.

METHODS

A total of 26 patients with ADPKD and 24 control group, matched for age and sex, were enrolled, and we have assessed inflammatory indexes, mineral metabolism, metabolic state and markers of atherosclerosis and endothelial dysfunction (carotid intima media thickness (IMT), ankle brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI), left ventricular mass index (LVMI)) and cardiopulmonary exercise testing (CPET), maximal O2 uptake (V'O2max), and O2 uptake at lactic acid threshold (V'O2@LT).

RESULTS

The ADPKD patients compared to control group, showed a significant higher mean value of LVMI, RRI, homocysteine (Hcy), Homeostasis Model Assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), Cardiac-troponinT (cTnT) and intact parathyroid hormone (iPTH) (p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, p=0.007, p=0.019; respectively), and a lower value of FMD and 25-hydroxyvitaminD (25-OH-VitD) (p<0.001, p<0.001) with reduced parameters of exercise tolerance, as V'O2max, V'O2max/Kg and V'O2max (% predicted) (p<0.001, p<0.001, p=0.018; respectively), and metabolic response indexes (V'O2@LT, V'O2 @LT%, V'O2@LT/Kg,) (p<0.001, p=0.14, p<0.001; respectively). Moreover, inflammatory indexes were significantly higher in ADPKD patients, and we found a positive correlation between HOMA-IR and C-reactive protein (CRP) (r=0.507, p=0.008), and a negative correlation between HOMA-IR and 25-OH-VitD (r=-0.585, p=0.002).

CONCLUSION

In our study, ADPKD patients, in the early stages of disease, showed a greater insulin resistance, endothelial dysfunction, inflammation and mineral metabolism disorders, respect to control group. Moreover, these patients presented reduced tolerance to stress, and decreased anaerobic threshold to CPET. Our results indicate a major and early cardiovascular risk in ADPKD patients. Therefore early and noninvasive markers of cardiovascular risk and CPET should be carried out, in ADPKD patients, in the early stages of disease, despite the cost implication.

摘要

背景/目的:心血管疾病是常染色体显性多囊肾病(ADPKD)患者发病率和死亡率的最常见原因,通常在肾功能衰竭之前发生,其发病机制尚未得到很好的阐明。本研究的目的是在疾病早期确定年轻 ADPKD 患者心血管风险的早期和非侵入性标志物。

方法

共纳入 26 例 ADPKD 患者和 24 例年龄和性别匹配的对照组,并评估了炎症指标、矿物质代谢、代谢状态以及动脉粥样硬化和内皮功能障碍的标志物(颈动脉内膜中层厚度(IMT)、踝臂指数(ABI)、血流介导的扩张(FMD)、肾阻力指数(RRI)、左心室质量指数(LVMI))和心肺运动测试(CPET),最大摄氧量(V'O2max)和乳酸阈摄氧量(V'O2@LT)。

结果

与对照组相比,ADPKD 患者的平均 LVMI、RRI、同型半胱氨酸(Hcy)、稳态模型评估胰岛素抵抗(HOMA-IR)、血清尿酸(SUA)、心脏肌钙蛋白 T(cTnT)和完整甲状旁腺激素(iPTH)显著升高(p<0.001,p<0.001,p<0.001,p<0.001,p<0.001,p=0.007,p=0.019;分别),FMD 和 25-羟维生素 D(25-OH-VitD)水平降低(p<0.001,p<0.001),运动耐量参数降低,如 V'O2max、V'O2max/Kg 和 V'O2max(%预测)(p<0.001,p<0.001,p=0.018;分别)和代谢反应指标(V'O2@LT、V'O2@LT%、V'O2@LT/Kg)(p<0.001,p=0.14,p<0.001;分别)。此外,ADPKD 患者的炎症指标显著升高,我们发现 HOMA-IR 与 C 反应蛋白(CRP)之间呈正相关(r=0.507,p=0.008),HOMA-IR 与 25-OH-VitD 之间呈负相关(r=-0.585,p=0.002)。

结论

在我们的研究中,ADPKD 患者在疾病早期就表现出更大的胰岛素抵抗、内皮功能障碍、炎症和矿物质代谢紊乱,与对照组相比。此外,这些患者在 CPET 中表现出应激耐受力降低和无氧阈值降低。我们的结果表明 ADPKD 患者存在较大的心血管风险。因此,尽管成本较高,但在疾病早期,ADPKD 患者也应进行心血管风险的早期和非侵入性标志物和 CPET 检查。

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