Glymphatic Dysfunction in Patients With End-Stage Renal Disease

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

doi:10.3389/fneur.2021.809438

Cited by 13 publications

(6 citation statements)

References 34 publications

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“…The findings of our study are consistent with the results of previous studies that confirmed glymphatic system dysfunction in patients with non-dialysis CKD 17 and ESKD patients on dialysis [ 16 ]. Previous studies also showed that patients with ESKD have a higher prevalence of cognitive impairment with worse results on neurocognitive tests compared to the general population [ 18 , 19 ].…”

Section: Discussionsupporting

confidence: 93%

“…Impairment of the glymphatic system has been implicated in the pathogenesis of cognitive impairment in various neurological disorders [ 6–8 ]. In our previous studies, patients with various stages of chronic kidney disease (CKD) showed - abnormalities in the glymphatic system [ 16 , 17 ]. However, it was unclear whether these abnormal findings of the glymphatic system could be improved through KRT, or not.…”

Section: Introductionmentioning

confidence: 99%

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Changes in the glymphatic system before and after dialysis initiation in patients with end-stage kidney disease

Lee,

Park,

Heo

et al. 2023

Renal Failure

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Introduction The aims of this study were to evaluate 1) glymphatic system function in patients with end-stage kidney disease (ESKD) before initiating dialysis compared to healthy controls, and 2) changes in the glymphatic system function after kidney replacement therapy including dialysis in patients with ESKD using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. Materials and methods This study was prospectively conducted at a single hospital. We enrolled 14 neurologically asymptomatic patients who first initiated hemodialysis or peritoneal dialysis for ESKD and 17 healthy controls. Patients had magnetic resonance imaging scans before initiating dialysis and again 3 months after initiating dialysis and the DTI-ALPS index was calculated. We compared the DTI-ALPS index before and after the initiation of dialysis and compared the DTI-ALPS index between the patients with ESKD and healthy control. Results There were differences in the DTI-ALPS index between ESKD patients before initiating dialysis and healthy controls (1.342 vs. 1.633, p = 0.003). DTI-ALPS index between ESKD patients before initiating dialysis and those after dialysis were not different (1.342 vs. 1.262, p = 0.386). There was a positive correlation between DTI-ALPS index and phosphate ( r = 0.610, p = 0.020) in patients with ESKD. Conclusion We confirmed the presence of glymphatic dysfunction in patients with ESKD. However, there was no difference in the glymphatic system before and after dialysis initiation. This finding may be related to uremic toxins that are not removed by dialysis in patients with ESKD. This study can be used for the development of pathophysiology of patients with ESKD.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Changes in the glymphatic system before and after dialysis initiation in patients with end-stage kidney disease

Lee,

Park,

Heo

et al. 2023

Renal Failure

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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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“…The averaged diffusivities were obtained in each ROI, excluding the maximum and minimum values, from among the various voxels for each fiber on the same x, y, and z axes (projection, association, and subcortical fibers). The DTI-ALPS index was derived using the formula below ( 6 , 15 , 17 ):…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, it can be expected that dysfunction of glymphatic system may be present in patients with CKD. The DTI-ALPS index has previously been utilized to indicate glymphatic system dysfunction in ESRD patients, and the method's feasibility for assessing glymphatic system function in ESRD patients was verified ( 15 ). However, no research has been done on the function of the glymphatic system in patients with early CKD.…”

Section: Introductionmentioning

confidence: 99%

Glymphatic system dysfunction in patients with early chronic kidney disease

et al. 2022

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IntroductionIt is a recent finding that glymphatic system dysfunction contributes to various neurological problems. The purpose of this research was to assess the function of the glymphatic system in neurologically asymptomatic early chronic kidney disease (CKD) patients and healthy controls, using diffusion tensor image analysis along perivascular space (DTI-ALPS) index.MethodsIn a prospective study, we included patients with early CKD who were asymptomatic for neurological issues and obtained clinical and laboratory data. In all participants, brain magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was conducted. We used DSI program for DTI preprocessing and DTI-ALPS index estimation. The DTI-ALPS index was compared between patients with early CKD and healthy controls, and the association between clinical characteristics and the DTI-ALPS index was investigated.ResultsEighteen patients with early CKD and 18 healthy controls were included in this study. Patients with early CKD had lower DTI-ALPS index than healthy controls (1.259 ± 0.199 vs. 1.477 ± 0.232, p = 0.004). In the correlation analysis, the DTI-ALPS index had no significant relationship with other clinical factors.ConclusionWe suggest dysfunction of glymphatic system in patients with early chronic kidney disease using the DTI-ALPS index. This may be related to the pathophysiology of neurological problems including impairment of cognition in patients with early CKD.

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Glymphatic Dysfunction in Patients With End-Stage Renal Disease

Cited by 13 publications

References 34 publications

Changes in the glymphatic system before and after dialysis initiation in patients with end-stage kidney disease

Changes in the glymphatic system before and after dialysis initiation in patients with end-stage kidney disease

Vascular risk factors and astrocytic marker for the glymphatic system activity

Glymphatic system dysfunction in patients with early chronic kidney disease

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