Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, China.
The National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China.
Front Endocrinol (Lausanne). 2023 Jul 25;14:1215977. doi: 10.3389/fendo.2023.1215977. eCollection 2023.
The potential relationship between Klotho and cognitive function is limited and controversial. This study aimed to quantify the association of Klotho and cognitive impairment in chronic kidney disease (CKD) patients with albuminuria.
Serum Klotho was measured by enzyme-linked immunosorbent assay. Patients with urine albumin to creatinine ratio (UACR) > 30mg/g from the National Health and Nutrition Survey (NHANES) 2011-2014 were divided into 4 groups according to the quartile of Klotho. Cognitive function was examined using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Digit Symbol Substitution Test (DSST), and Animal Fluency Test. The relationship between Klotho and cognitive function was analyzed by multivariable regression and subgroup analysis.
Among 368 CKD patients with albuminuria, we found that Klotho was negatively associated with creatinine, and positively associated with hemoglobin, and estimated glomerular filtration rate. No significant linear relationship was showed between Klotho (as a continuous variable) and cognitive function. When regarded Klotho as a category variable, patients in the quartile 3 group were at a better cognitive performance for CEARD-word learning subset and DSST, especially in the CKD patients with 30 mg/g < UACR <300 mg/g, but not in participants with UACR > 300 mg/g.
The increased Klotho was associated with an increased cognitive function in CKD patients with microalbuminuria. Further studies are needed to demonstrate whether Klotho may be a beneficial biomarker of cognitive health and neurodegeneration.
Klotho 与认知功能之间的潜在关系有限且存在争议。本研究旨在量化 Klotho 与伴有白蛋白尿的慢性肾脏病（CKD）患者认知障碍的相关性。
采用酶联免疫吸附法测定血清 Klotho。根据 Klotho 的四分位数，将 2011-2014 年国家健康和营养调查（NHANES）中尿白蛋白与肌酐比值（UACR）>30mg/g 的患者分为 4 组。采用认知障碍评估 Consortium to Establish a Registry for Alzheimer's Disease（CERAD）、数字符号替代测试（DSST）和动物流畅性测试来评估认知功能。采用多变量回归和亚组分析来分析 Klotho 与认知功能之间的关系。
在 368 例伴有白蛋白尿的 CKD 患者中，我们发现 Klotho 与肌酐呈负相关，与血红蛋白和估算肾小球滤过率呈正相关。Klotho（作为连续变量）与认知功能之间未显示出显著的线性关系。当将 Klotho 视为分类变量时，第 3 四分位数组的患者在 CERAD 单词学习子集中以及 DSST 的认知表现更好，尤其是在 UACR 为 30mg/g<UACR<300mg/g 的 CKD 患者中，但在 UACR>300mg/g 的参与者中并非如此。
Klotho 水平升高与伴有微量白蛋白尿的 CKD 患者认知功能提高有关。需要进一步的研究来证明 Klotho 是否可能成为认知健康和神经退行性变的有益生物标志物。
