From the Departments of Epidemiology (S.S., L.G.M.C., M.d.G., A.H., O.H.F., M.W.V., A.D., M.A.I.), Radiology (L.G.M.C., M.d.G., A.v.d.L., M.W.V., M.A.I.), Medical informatics (M.d.G.), Internal Medicine (E.J.H.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands.
Neurology. 2015 Jul 14;85(2):154-61. doi: 10.1212/WNL.0000000000001741. Epub 2015 Jun 17.
To investigate the association of kidney function with white matter microstructural integrity.
We included 2,726 participants with a mean age of 56.6 years (45% men) from the population-based Rotterdam Study. Albumin-to-creatinine ratio, and estimated glomerular filtration rate (eGFR), using serum cystatin C (eGFRcys) and creatinine (eGFRcr), were measured to evaluate kidney function. Diffusion-MRI was used to assess microstructural integrity of the normal-appearing white matter. Multiple linear regression models, adjusted for macrostructural MRI markers and cardiovascular risk factors, were used to model the association of kidney function with white matter microstructure.
Participants had average eGFRcr of 86.1 mL/min/1.73 m(2), average eGFRcys of 86.2 mL/min/1.73 m(2), and median albumin-to-creatinine ratio of 3.4 mg/g. Lower eGFRcys was associated with worse global white matter microstructural integrity, reflected as lower fractional anisotropy (standardized difference per SD: -0.053, 95% confidence interval [CI]: -0.092, -0.014) and higher mean diffusivity (0.036, 95% CI: 0.001, 0.070). Similarly, higher albumin-to-creatinine ratio was associated with lower fractional anisotropy (-0.044, 95% CI: -0.078, -0.011). There was no linear association between eGFRcr and white matter integrity. Subgroup analyses showed attenuation of the associations after excluding subjects with hypertension. The associations with global diffusion tensor imaging measures did not seem to be driven by particular tracts, but rather spread across multiple tracts in various brain regions.
Reduced kidney function is associated with worse white matter microstructural integrity. Our findings highlight the importance for clinicians to consider concomitant macro- and microstructural changes of the brain in patients with impaired kidney function.
研究肾功能与脑白质微观结构完整性之间的关系。
我们纳入了 2726 名平均年龄为 56.6 岁（45%为男性）的来自于人群为基础的鹿特丹研究的参与者。白蛋白/肌酐比值和估计肾小球滤过率（eGFR），使用血清胱抑素 C（eGFRcys）和肌酐（eGFRcr）来评估肾功能。使用弥散 MRI 评估正常外观脑白质的微观结构完整性。采用多元线性回归模型，调整宏观结构 MRI 标志物和心血管危险因素，对肾功能与脑白质微观结构之间的关系进行建模。
参与者的平均 eGFRcr 为 86.1mL/min/1.73m2，平均 eGFRcys 为 86.2mL/min/1.73m2，中位白蛋白/肌酐比值为 3.4mg/g。较低的 eGFRcys 与较差的全脑白质微观结构完整性相关，表现为较低的各向异性分数（标准化差：-0.053，95%置信区间[CI]：-0.092，-0.014）和较高的平均弥散系数（0.036，95%CI：0.001，0.070）。同样，较高的白蛋白/肌酐比值与较低的各向异性分数（-0.044，95%CI：-0.078，-0.011）相关。eGFRcr 与脑白质完整性之间无线性关系。亚组分析显示，排除高血压患者后，这些关联减弱。与全脑弥散张量成像测量相关的关联似乎不是由特定的束引起的，而是分布在大脑不同区域的多个束上。
肾功能下降与脑白质微观结构完整性较差有关。我们的研究结果强调了临床医生在考虑伴有肾功能受损的患者时，不仅要考虑大脑的宏观结构变化，还要考虑微观结构变化的重要性。
