Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Ageing Res Rev. 2022 Dec;82:101762. doi: 10.1016/j.arr.2022.101762. Epub 2022 Oct 29.
This study aimed to evaluate the bidirectional association between the kidney dysfunction and the brain health, including structural and functional abnormalities.
Systematic review and meta-analysis with network meta-analysis for outcomes with different estimated glomerular filtration rate (eGFR) ranges.
PubMed, Embase database, Cochrane library and Web of Science (up to Dec. 2021).
Longitudinal studies that provided evidence of the impact of kidney function estimated from eGFR and urine albumin-to-creatinine ratio (UACR) or chronic kidney disease (CKD) on structural and functional brain abnormalities, and those that provided evidence of the opposite relationship. Studies with study population mean age under 18 years old were excluded.
Two independent reviewers screened the included studies, extracted the data, and assessed the risk of bias. We performed a random-effects meta-analysis and a network meta-analysis for outcomes with compatible data. We assessed the risk of bias using the Newcastle-Ottawa Quality Assessment Scale criteria (NOS). Subgroup and sensitivity analyses were conducted to explore heterogeneity in the meta-analyses. Inconsistency analyses using the node-splitting method were performed to confirm the results of network meta-analysis.
A total of 53 studies with 3037,357 participants were included in the current systematic review. Among these, 16 provided evidence of structural brain abnormalities, and 38 provided evidence of cognitive impairment and dementia. Analysis of evidence of categorical kidney function showed a positive association between kidney dysfunction and cerebral small vessel disease (cSVD) (relative risk (RR) 1.77, 95% confidence interval (CI) 1.40-2.24, I = 0.0%), but such results were not found in the analyses of evidence where the kidney function was measured as a continuous variable. Meanwhile, analysis of 28 prior longitudinal studies with 194 compatible sets of data showed that the worse kidney function as categorical variables was related to a greater risk of global brain cognitive disorder (RR 1.28, 95% CI 1.20-1.36, I = 82.5%).
In this systematic review and meta-analysis, we found a positive association between CKD and functional brain disorders. However, the relationship between the kidney dysfunction and structural abnormalities in the brain remains controversial. As for the opposite relationship, structural brain abnormalities, especially cerebral microbleeds and silent infarction, but not functional brain abnormalities, are associated with worse renal function. In addition, a higher UACR, but not a lower eGFR, was associated with a higher risk of Alzheimer's disease and vascular dementia.
本研究旨在评估肾功能障碍与大脑健康之间的双向关联，包括结构和功能异常。
系统评价和网络荟萃分析，对不同估计肾小球滤过率（eGFR）范围的结果进行荟萃分析。
PubMed、Embase 数据库、Cochrane 图书馆和 Web of Science（截至 2021 年 12 月）。
提供 eGFR 和尿白蛋白/肌酐比值（UACR）或慢性肾脏病（CKD）估计的肾功能对结构和功能脑异常影响证据的纵向研究，以及提供相反关系证据的研究。排除研究人群平均年龄小于 18 岁的研究。
两名独立审查员筛选纳入研究、提取数据并评估偏倚风险。我们进行了随机效应荟萃分析和网络荟萃分析，以获得具有兼容数据的结果。我们使用纽卡斯尔-渥太华质量评估量表（NOS）标准评估偏倚风险。进行亚组和敏感性分析以探索荟萃分析中的异质性。使用节点分裂法进行不一致性分析以确认网络荟萃分析的结果。
本系统评价共纳入 53 项研究，共 3037357 名参与者。其中 16 项提供了结构脑异常的证据，38 项提供了认知障碍和痴呆的证据。对分类肾功能证据的分析表明，肾功能障碍与脑小血管疾病（cSVD）之间存在正相关（相对风险 1.77，95%置信区间 1.40-2.24，I = 0.0%），但在分析作为连续变量测量的肾功能证据时，并未发现这种结果。同时，对 28 项具有 194 组兼容数据的前瞻性纵向研究进行分析表明，作为分类变量的肾功能越差，发生全球脑认知障碍的风险越高（RR 1.28，95%CI 1.20-1.36，I = 82.5%）。
在本系统评价和荟萃分析中，我们发现 CKD 与功能性脑障碍之间存在正相关。然而，肾功能障碍与大脑结构异常之间的关系仍存在争议。对于相反的关系，结构脑异常，特别是脑微出血和无症状性梗死，但不是功能性脑异常，与更差的肾功能相关。此外，较高的 UACR，而不是较低的 eGFR，与阿尔茨海默病和血管性痴呆的风险增加相关。
