Glymphatic system dysfunction in patients with early chronic kidney disease

Heo, Chang Min; Lee, Dong Ah; Park, Kang Min; Lee, Yoo Jin; Park, Si Hyung; Kim, Yang Wook; Ko, Junghae; Yoo, Byeong Cheol; Park, Bong Soo

doi:10.3389/fneur.2022.976089

Cited by 15 publications

(9 citation statements)

References 33 publications

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“…With evidence from bench to clinical, impairment of aquaporin function leads to kidney diseases [ 40 ]. Impaired glymphatic activity was observed in chronic kidney disease, from mild to advanced stages [ 41 , 42 ]. Besides, our results also support this renal-brain association in water metabolism that blood Cr and BUN correlated with the DTI-ALPS index.…”

Section: Discussionmentioning

confidence: 99%

Vascular risk factors and astrocytic marker for the glymphatic system activity

et al. 2023

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Objectives Glymphatic system maintains brain fluid circulation via active transportation of astrocytic aquaporin-4 in perivascular space. The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) is an established method measuring perivascular glymphatic activity, but comprehensive investigations into its influential factors are lacking. Methods Community-dwelling older adults underwent brain MRI scans, neuropsychiatric, and multi-domain assessments. Blood biomarker tests included glial fibrillary acidic protein (GFAP) for astrocyte injury. Results In 71 enrolled participants, the DTI-ALPS index was associated with modifiable factors, including lipid profile (high-density lipoprotein, r = 0.396; very-low-density lipoprotein, r = − 0.342), glucose intolerance (diabetes mellitus, standardized mean difference (SMD) = 0.7662; glycated hemoglobin, r = − 0.324), obesity (body mass index, r = − 0.295; waist, r = − 0.455), metabolic syndrome (SMD = − 0.6068), cigarette-smoking (SMD = − 0.6292), and renal clearance (creatinine, r = − 0.387; blood urea nitrogen, r = − 0.303). Unmodifiable associative factors of DTI-ALPS were age (r = − 0.434) and sex (SMD = 1.0769) (all p < 0.05). A correlation of DTI-ALPS and blood GFAP was noticed (r = − 0.201, one-tailed t-test for the assumption that astrocytic injury impaired glymphatic activity, p = 0.046). Their cognitive correlations diverged, domain-specific for DTI-ALPS (Facial Memory Test, r = 0.272, p = 0.022) but global cognition-related for blood GFAP (MoCA, r = − 0.264, p = 0.026; ADAS-cog, r = 0.304, p = 0.010). Conclusion This correlation analysis revealed multiple modifiable and unmodifiable association factors to the glymphatic image marker. The DTI-ALPS index correlated with various metabolic factors that are known to increase the risk of vascular diseases such as atherosclerosis. Furthermore, the DTI-ALPS index was associated with renal indices, and this connection might be a link of water regulation between the two systems. In addition, the astrocytic biomarker, plasma GFAP, might be a potential marker of the glymphatic system; however, more research is needed to confirm its effectiveness.

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Section: Discussionmentioning

confidence: 99%

Vascular risk factors and astrocytic marker for the glymphatic system activity

et al. 2023

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“…Besides, a recent study suggests that the glymphatic system may be suppressed in early CKD [43] . In addition, cerebral blood flow has been identified increased in CKD [44] , possibly through endothelial or glial cells, which may change the way substances exchanged between blood and neurons, causing the impairment of the blood-brain barrier and glymphatic system.…”

Section: Discussionmentioning

confidence: 99%

Cognitive Impairment in Chronic Kidney Disease Is Associated with Glymphatic System Dysfunction

Xu¹,

Wang²,

Sun³

et al. 2023

Kidney Dis

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Introduction: This study was designed to explore the associations between impaired cognition in chronic kidney disease (CKD) patients and the dysfunction of the glymphatic system. Method: Data were obtained from 77 CKD patients and 50 age-matched healthy control individuals from the First Affiliated Hospital of Zhengzhou University. CKD patients were stratified into with and without impaired cognitive function. T2-weighted magnetic resonance imaging results were used to assess area ratios for the perivascular space and ventricles in participants, while the Montreal Cognitive Assessment and the Mini-Mental State Examination were employed to measure cognitive function. Correlations between the perivascular space or ventricle area ratios and cognitive impairment were assessed in CKD patients. Results: Significant increases in the burden of enlarged perivascular spaces in the frontal cortex and basal ganglia were observed in CKD patients with cognitive impairment relative to those without such impairment, with a concomitant increase in analyzed ventricle area ratios. Enlarged perivascular spaces in the frontal cortex, basal ganglia and increased area ratios of lateral ventricles and 4th ventricle exhibited relatively high sensitivity and specificity as means of differing between the CKD patients with and without cognitive impairment. Conclusion: These results indicate that the burden of enlarged perivascular spaces in the frontal cortex and basal ganglia and increases in ventricle area ratio values may offer utility as biomarkers that can aid in detection of even mild cognitive decline in individuals with CKD. The dysfunction of the glymphatic system may play a key role in the pathogenesis of CKD-related cognitive impairment.

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“…This may cause cerebral hypoxia, which may likewise induce cognitive dysfunction [ 223 ]. A study by Chang Min Heo and his team showed that patients with chronic kidney disease already have dysfunction of the glymphatic system in the early stages of the disease [ 222 , 224 ]. This is mainly due to two factors.…”

Section: The Critical Role Of the Cerebral Lymphatic System As A Brid...mentioning

confidence: 99%

Connecting the Dots: The Cerebral Lymphatic System as a Bridge Between the Central Nervous System and Peripheral System in Health and Disease

Zhao¹,

Sun²,

Zhang³

et al. 2024

Aging and disease

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As a recently discovered waste removal system in the brain, cerebral lymphatic system is thought to play an important role in regulating the homeostasis of the central nervous system. Currently, more and more attention is being focused on the cerebral lymphatic system. Further understanding of the structural and functional characteristics of cerebral lymphatic system is essential to better understand the pathogenesis of diseases and to explore therapeutic approaches. In this review, we summarize the structural components and functional characteristics of cerebral lymphatic system. More importantly, it is closely associated with peripheral system diseases in the gastrointestinal tract, liver, and kidney. However, there is still a gap in the study of the cerebral lymphatic system. However, we believe that it is a critical mediator of the interactions between the central nervous system and the peripheral system.

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Glymphatic system dysfunction in patients with early chronic kidney disease

Cited by 15 publications

References 33 publications

Vascular risk factors and astrocytic marker for the glymphatic system activity

Vascular risk factors and astrocytic marker for the glymphatic system activity

Cognitive Impairment in Chronic Kidney Disease Is Associated with Glymphatic System Dysfunction

Connecting the Dots: The Cerebral Lymphatic System as a Bridge Between the Central Nervous System and Peripheral System in Health and Disease

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