Cerebrovascular pulsatility index is higher in chronic kidney disease.
Cerebrovascular pulsatility index is higher in chronic kidney disease.
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DOI：
10.14814/phy2.15561
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发表时间：
2023-01
影响因子：
2.5
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中科院分区：
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慢性肾病（CKD）患者更可能死于心血管疾病，包括脑血管疾病，而不是进展为终末期肾病。以脑血管反应性降低、脑灌注不足和脑内脉动流增加为特征的脑血管功能障碍先于痴呆发作，并与认知功能障碍相关。然而，在非透析依赖性CKD中是否存在脑血管功能受损在很大程度上尚不清楚。使用经颅多普勒，我们比较了3-4期CKD患者与年龄匹配的健康对照组的大脑中动脉（MCA）对高碳酸血症的血流速度反应（血压和呼气末CO2标准化;脑血管反应性的测量）和MCA搏动指数（PI;脑血管僵硬度的测量）。我们还管理了NIH认知工具箱（认知功能），测量了颈动脉-股动脉脉搏波速度（PWV;主动脉僵硬度），并评估了与研究参与者血清孵育的人脑内皮细胞的体外一氧化氮（NO）和活性氧（ROS）产生。CKD患者的MCA PI高于对照组;然而，两组之间对高碳酸血症的标准化MCA血流速度反应无差异。在中年和老年人的验证队列中观察到类似的结果，除以估计的肾小球滤过率（eGFR）中位数。MCA PI与较大弹性动脉僵硬度（颈动脉-股动脉PWV）、较差执行功能（试验B时间）、较低eGFR和较高离体ROS产生相关。这些数据表明，肾功能受损与脑血管僵硬度增加相关，这可能导致CKD患者认知功能障碍的已知风险增加。与匹配对照相比，非透析依赖性CKD患者的大脑中动脉（MCA）搏动指数（PI）较高，但脑血管对高碳酸血症的反应性保持不变。MCA PI与脉搏波速度和与研究参与者血清孵育的人脑内皮细胞的离体活性氧产生呈正相关，与执行功能呈负相关。需要进一步的研究在更大的队列中证实这些结果，并描述CKD患者的动脉僵硬度、脑血管功能和认知障碍之间的联系机制。
Patients with chronic kidney disease (CKD) are more likely to die of cardiovascular diseases, including cerebrovascular disease, than to progress to end‐stage kidney disease. Cerebrovascular dysfunction, characterized by reduced cerebrovascular reactivity, cerebral hypoperfusion, and increased pulsatile flow within the brain, precedes the onset of dementia and is linked to cognitive dysfunction. However, whether impaired cerebrovascular function is present in non‐dialysis dependent CKD is largely unknown. Using transcranial Doppler, we compared middle cerebral artery (MCA) blood velocity response to hypercapnia (normalized for blood pressure and end‐tidal CO2; a measure of cerebrovascular reactivity) and MCA pulsatility index (PI; a measure of cerebrovascular stiffness) in patients with stage 3–4 CKD vs. age‐matched healthy controls. We also administered the NIH cognitive toolbox (cognitive function), measured carotid‐femoral pulse‐wave velocity (PWV; aortic stiffness), and assessed ex vivo nitric oxide (NO) and reactive oxygen species (ROS) production from human brain endothelial cells incubated with serum obtained from study participants. MCA PI was higher in patients with CKD vs. controls; however, normalized MCA blood velocity response to hypercapnia did not differ between groups. Similar results were observed in a validation cohort of midlife and older adults divided by the median estimated glomerular filtration rate (eGFR). MCA PI was associated with greater large‐elastic artery stiffness (carotid‐femoral PWV), worse executive function (trails B time), lower eGFR, and higher ex vivo ROS production. These data suggest that impaired kidney function is associated with greater cerebrovascular stiffness, which may contribute to the known increased risk for cognitive impairment in patients with CKD. Middle cerebral artery (MCA) pulsatility index (PI) was higher, but cerebrovascular reactivity to hypercapnia was preserved in patients with non‐dialysis dependent CKD as compared to matched controls. MCA PI was positively associated with pulse‐wave velocity and ex vivo reactive oxygen species production from human brain endotheial cells incubated with serum from study participants and inversely associated with executive function. Further research is needed to confirm these results in larger cohorts and to delineate the mechanisms linking arterial stiffness, cerebrovascular function, and cognitive impairment in patients with CKD.