Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
Am J Kidney Dis. 2023 Mar;81(3):261-269.e1. doi: 10.1053/j.ajkd.2022.07.013. Epub 2022 Sep 27.
RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is a risk factor for cognitive decline, but evidence is limited on its etiology and morphological manifestation in the brain. We evaluated the association of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) with structural brain abnormalities visible on magnetic resonance imaging (MRI). We also assessed whether this association was altered when different filtration markers were used to estimate GFR.
Cross-sectional study nested in a cohort study.
SETTING & PARTICIPANTS: 1,527 participants in the Atherosclerosis Risk in Communities (ARIC) Study.
Log(UACR) and eGFR based on cystatin C, creatinine, cystatin C and creatinine in combination, or β-microglobulin (B2M).
Brain volume reduction, infarcts, microhemorrhages, white matter lesions.
Multivariable linear and logistic regression models fit separately for each predictor based on a 1-IQR difference in the predictor value.
Each 1-IQR lower eGFR was associated with reduced cortex volume (regression coefficient: -0.07 [95% CI, -0.12 to-0.02]), greater white matter hyperintensity volume (logarithmically transformed; regression coefficient: 0.07 [95% CI, 0.01-0.15]), and lower white matter fractional anisotropy (regression coefficient: -0.08 [95% CI, -0.17 to-0.01]). The results were similar when eGFR was estimated with different equations based on cystatin C, creatinine, a combination of cystatin C and creatinine, or B2M. Higher log(UACR) was similarly associated with these outcomes as well as brain infarcts and microhemorrhages (odds ratios per 1-IQR-fold greater UACR of 1.31 [95% CI, 1.13-1.52] and 1.30 [95% CI, 1.12-1.51], respectively). The degree to which brain volume was lower in regions usually susceptible to Alzheimer disease and LATE (limbic-predominant age-related TDP-43 [Tar DNA binding protein 43] encephalopathy) was similar to that seen in the rest of the cortex.
No inference about longitudinal effects due to cross-sectional design.
We found eGFR and UACR are associated with structural brain damage across different domains of etiology, and eGFR- and UACR-related brain atrophy is not selective for regions typically affected by Alzheimer disease and LATE. Hence, Alzheimer disease or LATE may not be leading contributors to neurodegeneration associated with CKD.
慢性肾脏病（CKD）是认知能力下降的一个危险因素，但有关其病因学和大脑形态表现的证据有限。我们评估了估算肾小球滤过率（eGFR）和尿白蛋白/肌酐比值（UACR）与磁共振成像（MRI）上可见的结构性脑异常之间的相关性。我们还评估了当使用不同的滤过标志物来估计 GFR 时，这种相关性是否会发生改变。
队列研究中的横断面研究。
动脉粥样硬化风险社区（ARIC）研究中的 1527 名参与者。
基于半胱氨酸蛋白酶抑制剂 C、肌酐、半胱氨酸蛋白酶抑制剂 C 和肌酐的组合或β-微球蛋白（B2M）的 UACR 和 eGFR 的对数。
每个 1-IQR 更低的 eGFR 与皮质体积减少（回归系数：-0.07[95%CI，-0.12 至-0.02]）、更大的白质高信号体积（对数转换；回归系数：0.07[95%CI，0.01-0.15]）和更低的白质各向异性（回归系数：-0.08[95%CI，-0.17 至-0.01]）相关。当 eGFR 基于半胱氨酸蛋白酶抑制剂 C、肌酐、半胱氨酸蛋白酶抑制剂 C 和肌酐的组合或 B2M 的不同方程进行估计时，结果是相似的。较高的 UACR 对数与这些结果以及脑梗死和微出血（UACR 每增加 1-IQR 倍的比值比为 1.31[95%CI，1.13-1.52]和 1.30[95%CI，1.12-1.51]）也存在类似的相关性。在通常易受阿尔茨海默病和 LATE（边缘为主的与年龄相关的 TDP-43[Tar DNA 结合蛋白 43]脑病）影响的区域，脑体积降低的程度与大脑其他区域相似。
由于横断面设计，没有关于纵向效应的推断。
我们发现 eGFR 和 UACR 与不同病因领域的结构性脑损伤相关，并且与 eGFR 和 UACR 相关的脑萎缩并非仅针对通常受阿尔茨海默病和 LATE 影响的区域。因此，阿尔茨海默病或 LATE 可能不是与 CKD 相关的神经退行性变的主要原因。
