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Association of kidney function and brain health: A systematic review and meta-analysis of cohort studies

ABSTRACT

Objective: This study aimed to evaluate the bidirectional association between the kidney dysfunction and the brain health, including structural and functional abnormalities.

Design: Systematic review and meta-analysis with network meta-analysis for outcomes with different estimated glomerular filtration rate ranges. Data sources: PubMed, Embase database, Cochrane library and Web of Science.

Eligibility criteria for selecting studies: Longitudinal studies that provided evidence of the impact of kidney function estimated from estimated glomerular filtration rate and urine albumin-to-creatinine ratio or chronic kidney disease on structural and functional brain abnormalities, and those that provided evidence of the opposite relationship. Studies with study population mean age under eighteen years old were excluded.

Main outcome measures: 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. 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.

Results: A total of fifty-three studies with three thousand thirty-seven to three hundred fifty-seven participants were included in the current systematic review. Among these, sixteen provided evidence of structural brain abnormalities, and thirty-eight 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 (relative risk one point seven seven, ninety-five percent confidence interval one point four zero to two point two four, I squared zero point zero percent, but such results were not found in the analyses of evidence where the kidney function was measured as a continuous variable. Meanwhile, analysis of twenty-eight prior longitudinal studies with one hundred ninety-four compatible sets of data showed that the worse kidney function as categorical variables was related to a greater risk of global brain cognitive disorder (relative risk one point two eight, ninety-five percent confidence interval one point two zero to one point three six,

I squared eighty-two point five percent. Conclusions: In this systematic review and meta-analysis, we found a positive association between chronic kidney disease 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 urine albumin-to-creatinine ratio, but not a lower estimated glomerular filtration rate, was associated with a higher risk of Alzheimer's disease and vascular dementia.

One. Introduction

Two. Methods

Two point two. Study inclusion

Two point three. Inclusion and exclusion criteria

Two point four. Data extraction and quality assessment

Two point five. Statistical analysis

Early-stage CKD is associated with cognitive decline in an oldest-old Chinese population.

Three. Results

Three point two. Meta-analyses and systematic review of the relationship between kidney function and cSVDs

Three point three. Categorical kidney function and cSVD

Three point four. The association between kidney function and cerebral volume

Three point five. Meta-analysis and literature review of relationship between kidney function and cognitive impairment or dementia

Three point six. Categorical kidney function and cognitive impairment and dementia

Three point seven. Network meta-analysis of the association between different eGFR range and cognitive impairment and dementia

Three point eight. Meta-analysis and literature review of the relationship between the brain health and kidney function

Three point nine. The effect of cognitive impairment and dementia on kidney function

Four. Discussion

Four point two. Underlying mechanisms

Four point three. Strengths and limitations

Four point four. Future implications

Four point five. Public Health Implications

Five. Conclusion

Ethical approval

Funding

Contributors

Copyright/license for publication

Transparency statement

Competing interests

Data Availability

Overview

The study evaluates the relationship between chronic kidney disease and various brain health disorders, revealing a positive association between kidney dysfunction and structural brain issues, while also examining the reciprocal effects. The findings suggest that chronic kidney disease may increase the risk of cognitive impairment and dementia, highlighting a complex interplay between these two health issues.

Key Points

1There is a positive association between chronic kidney disease (CKD) and functional brain disorders such as cognitive impairment.
2Structural brain abnormalities are linked to worse kidney function, but findings remain controversial regarding the nature of these associations.
3The study emphasizes the increasing prevalence of brain health issues among individuals with CKD.
4Subgroup analyses reveal varying degrees of risk depending on the severity of kidney dysfunction.
5Future prevention strategies are essential to address the growing public health concerns of both CKD and brain health disorders.

Details

Authors: Xingyao Tang, Yi-Peng Han, Yin-He Chai, Hong-Jian Gong, Hui Xu, Ikramulhaq Patel, Yu-Shun Qiao, Jin-Yan Zhang, Marly Augusto Cardoso, Jian-Bo Zhou
Category: Health and Medicine

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