Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, PR China; Department of Pediatric Urology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, PR China.
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, PR China.
EBioMedicine. 2021 Oct;72:103592. doi: 10.1016/j.ebiom.2021.103592. Epub 2021 Oct 4.
Alterations in the brain cortical structures of patients with chronic kidney disease (CKD) have been reported; however, the cause has not been determined yet. Herein, we used Mendelian randomization (MR) to reveal the causal effect of kidney damage on brain cortical structure.
Genome-wide association studies summary data of estimated glomerular filtration rate (eGFR) in 480,698 participants from the CKDGen Consortium were used to identify genetically predicted eGFR. Data from 567,460 individuals from the CKDGen Consortium were used to assess genetically determined CKD; 302,687 participants from the UK Biobank were used to evaluate genetically predicted albuminuria. Further, data from 51,665 patients from the ENIGMA Consortium were used to assess the relationship between genetic predisposition and reduced eGFR, CKD, and progressive albuminuria with alterations in cortical thickness (TH) or surficial area (SA) of the brain. Magnetic resonance imaging was used to measure the SA and TH globally and in 34 functional regions. Inverse-variance weighted was used as the primary estimate whereas MR Pleiotropy RESidual Sum and Outlier, MR-Egger and weighted median were used to detect heterogeneity and pleiotropy.
At the global level, albuminuria decreased TH (β = -0.07 mm, 95% CI: -0.12 mm to -0.02 mm, P = 0.004); at the functional level, albuminuria reduced TH of pars opercularis gyrus without global weighted (β = -0.11 mm, 95% CI: -0.16 mm to -0.07 mm, P = 3.74×10). No pleiotropy was detected.
Kidney damage causally influences the cortex structure which suggests the existence of a kidney-brain axis.
This study was supported by the Science and Technology Planning Project of Guangdong Province (Grant No. 2020A1515111119 and 2017B020227007), the National Key Research and Development Program of China (Grant No. 2018YFA0902803), the National Natural Science Foundation of China (Grant No. 81825016, 81961128027, 81772719, 81772728), the Key Areas Research and Development Program of Guangdong (Grant No. 2018B010109006), Guangdong Special Support Program (2017TX04R246), Grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, and Grants from the Guangdong Science and Technology Department (2020B1212060018).
已有报道称，慢性肾脏病（CKD）患者的大脑皮质结构发生改变，但病因尚未确定。在此，我们使用孟德尔随机化（MR）来揭示肾脏损伤对大脑皮质结构的因果影响。
使用来自 CKDGen 联盟的 480698 名参与者的估计肾小球滤过率（eGFR）全基因组关联研究汇总数据来识别遗传预测的 eGFR。使用来自 CKDGen 联盟的 567460 名个体的数据来评估遗传决定的 CKD；来自英国生物银行的 302687 名参与者用于评估遗传预测的白蛋白尿。此外，来自 ENIGMA 联盟的 51665 名患者的数据用于评估遗传易感性与 eGFR 降低、CKD 和进行性白蛋白尿与大脑皮质厚度（TH）或表面积（SA）变化之间的关系。磁共振成像用于测量全球和 34 个功能区的 SA 和 TH。逆方差加权是主要估计值，而 MR 多效性残余总和和异常值、MR-Egger 和加权中位数用于检测异质性和多效性。
在全球水平上，白蛋白尿降低了 TH（β=-0.07mm，95%CI：-0.12mm 至-0.02mm，P=0.004）；在功能水平上，白蛋白尿降低了没有全球加权的脑回外侧沟皮质厚度（β=-0.11mm，95%CI：-0.16mm 至-0.07mm，P=3.74×10）。未检测到多效性。
肾脏损伤可导致皮质结构发生变化，这表明存在肾脏-大脑轴。
本研究得到广东省科技计划项目（Grant No. 2020A1515111119 and 2017B020227007）、国家重点研发计划（Grant No. 2018YFA0902803）、国家自然科学基金（Grant No. 81825016, 81961128027, 81772719, 81772728）、广东省重点领域研发计划（Grant No. 2018B010109006）、广东省特支计划（2017TX04R246）、广东高校恶性肿瘤基因调控与靶向治疗重点实验室基金（Grant KLB09001）和广东省科技厅基金（2020B1212060018）的支持。
