Biological production of epicoccamide-aglycone and its cytotoxicity.

Epicoccamide (EPC) is an O-d-mannosylated acyltetramic acid of Epicoccum origin and is a bolaamphiphilic fungal polyketide. EPC displays weak toxicity against Staphylococcus aureus and HeLa cell lines. The EPC biosynthetic gene cluster was previously identified in Epicoccum nigrum and knockout of the glycosyltransferase gene (epcB) abolished EPC production. EPC-aglycone was expected in the epcB knockout but was not found. This study demonstrates that extractive culture using the hydrophobic resin Diaion HP-20 resulted in the production of EPC-aglycone, which was isolated using chromatographic separation techniques, and its structural identity was substantiated by chemical analyses. EPC-aglycone displayed strong antibacterial activity against Staphylococcus aureus, with the minimal inhibitory concentration of 1 µg/mL (64 µg/mL for EPC). EPC-aglycone displayed higher levels of growth inhibition against HeLa cell line (the half inhibitory concentration, 19 µM) and WI-38 (15 µM) cell line than EPC (76 µM and 38 µM vs. HeLa and WI-38, respectively). The dose-response curve fit of growth inhibition indicated that EPC-aglycone adopted a shallow curve (low slope factor), which was different from that of EPC, suggesting that their cellular targets are distinct from each other. This study substantiates that the d-mannose attachment is the final step in EPC biosynthesis, showcasing a glycosylation-mediated modulation of the biological activity of simple acyltetramic acid. This study also highlights the usefulness of extractive cultures in mining cryptic microbial natural products.

Difference in functional connectivity between end-stage renal disease patients with and without restless legs syndrome: A prospective study.

PURPOSE: The purpose of this study was to examine differences in functional connectivity between patients with end-stage renal disease (ESRD) with and without restless legs syndrome (RLS). In addition, the study aimed to identify any potential associations between RLS severity and functional connectivity. METHODS: We enrolled patients with ESRD who had been undergoing hemodialysis. Patients with and without RLS were separated into two groups. Using functional near-infrared spectroscopy (fNIRS) and a graph theory approach, we determined the functional connectivity of patients with ESRD. The data were collected during a 300-s resting state evaluation performed in the dialysis room prior to dialysis. RESULTS: Eighteen of 48 patients with ESRD were diagnosed with RLS, whereas 30 patients did not exhibit RLS symptoms. Notably, functional connectivity metrics differed significantly between patients with and without RLS. Specifically, patients with ESRD and RLS displayed higher values for mean clustering coefficient (0.474 vs. 0.352, p = 0.001), global efficiency (0.520 vs. 0.414, p = 0.001), strength (6.538 vs. 4.783, p = 0.001), and transitivity (0.714 vs. 0.521, p = 0.001), while values for diameter (5.451 vs. 7.338, p = 0.002), eccentricity (4.598 vs. 5.985, p = 0.004), and characteristic path length (2.520 vs. 3.271, p = 0.002) were lower in patients with ESRD and RLS compared to those without RLS. In addition, there were correlations between the RLS severity score and the assortative coefficient (r = 0.479, p = 0.044), the small-worldness index (r = -0.475, p = 0.046), and transitivity (r = 0.500, p = 0.034). CONCLUSIONS: We demonstrated differences in functional connectivity between patients with ESRD with and without RLS, which may shed light on the pathophysiology of RLS. Notably, a number of functional connectivity metrics demonstrated strong associations with RLS severity. Our study also confirmed the applicability of fNIRS as a tool for investigating functional connectivity in patients with RLS.

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

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.

Glymphatic System Function in Patients with Transient Global Amnesia.

BACKGROUND: The purpose of this study was to examine glymphatic system function in patients with transient global amnesia (TGA), as well as to conduct a recurrence analysis. METHODS: We enrolled patients with TGA and healthy controls from our hospital retrospectively. The patients and healthy controls were all scanned with the same 3T scanner, which included diffusion tensor imaging (DTI). We investigated the function of the glymphatic system using DTI analysis along the perivascular space (DTI-ALPS). The ALPS index was compared between patients with TGA and healthy controls, as well as between patients who had recurrent TGA events and those who had only a single TGA event. RESULTS: Seventy-two patients with TGA and 53 healthy controls were enrolled. Sixty-five patients with TGA had a single TGA event, while seven patients had recurrent TGA events. The ALPS index did not differ significantly between patients with TGA and healthy controls (1.665 vs. 1.618, p = 0.436). The ALPS index, on the other hand, varied significantly according to recurrence in patients with TGA. The ALPS index was significantly higher in patients with recurrent TGA events compared to those with a single event (1.928 vs. 1.636, p = 0.049). CONCLUSIONS: We investigated the glymphatic system function in patients with TGA compared to healthy controls for the first time using the DTI-ALPS method. We discovered that these groups did not differ in terms of glymphatic system function. However, glymphatic system function in patients with TGA may differ according to recurrence. Additional research is required to substantiate these findings.

Genetic localization of the orevactaene/epipyrone biosynthetic gene cluster in Epicoccum nigrum.

Epipyrone (EPN)-A (syn. orevactaene) is a polyketide compound of 3-d-galactosyl-4-hydroxy-2-pyrone with a modified heptaene acyl moiety, produced from Epicoccum nigrum and was reported to have various biological activities. Genome analysis identified a hypothetical EPN biosynthetic gene cluster (BGC) composed of the four genes epnABCD, which encode a highly-reducing fungal polyketide synthase, a glycosyltransferase, a cytochrome P450, and a transporter. The individual gene inactivation of epnABC resulted in the total loss of EPN production, while the inactivation of a nearby transcription factor-encoding gene had no effect on the production of EPN, substantiating that epnABCD is the EPN BGC. mRNA expression indicated no epnA transcription in the epnB knockout mutant and the occurrence of the bicistronic transcription of epnAB. This study defined an EPN BGC, which is the first blueprint reported for glycosylated 2-pyrone polyketide biosynthesis.

CLIPick: a sensitive peak caller for expression-based deconvolution of HITS-CLIP signals.

High-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP, also called CLIP-Seq) has been used to map global RNA-protein interactions. However, a critical caveat of HITS-CLIP results is that they contain non-linear background noise-different extent of non-specific interactions caused by individual transcript abundance-that has been inconsiderately normalized, resulting in sacrifice of sensitivity. To properly deconvolute RNA-protein interactions, we have implemented CLIPick, a flexible peak calling pipeline for analyzing HITS-CLIP data, which statistically determines the signal-to-noise ratio for each transcript based on the expression-dependent background simulation. Comprising of streamlined Python modules with an easy-to-use standalone graphical user interface, CLIPick robustly identifies significant peaks and quantitatively defines footprint regions within which RNA-protein interactions were occurred. CLIPick outperforms other peak callers in accuracy and sensitivity, selecting the largest number of peaks particularly in lowly expressed transcripts where such marginal signals are hard to discriminate. Specifically, the application of CLIPick to Argonaute (Ago) HITS-CLIP data were sensitive enough to uncover extended features of microRNA target sites, and these sites were experimentally validated. CLIPick enables to resolve critical interactions in a wide spectrum of transcript levels and extends the scope of HITS-CLIP analysis. CLIPick is available at: http://clip.korea.ac.kr/clipick/.

A reductase gene mppE controls yellow component production in azaphilone polyketide pathway of Monascus.

OBJECTIVES: To characterize a biosynthetic gene that is selectively involved in the biosynthesis of yellow or orange components in the azaphilone polyketide pathway of Monascus. RESULTS: A reductive modification is predicted to control the relative levels of reduced (yellow) and oxidized (orange and red) components in the pathway of azaphilone pigment biosynthesis in Monascus. Targeted inactivation of a reductase gene mppE enhanced orange and red pigment production whereas overexpression of the gene promoted yellow pigment production. The effect of mppE overexpression was dependent on culture methods, and augmented yellow pigmentation was evident in a submerged culture employing a chemically defined medium. CONCLUSIONS: MppE controls the biosynthesis of the yellow pigments, ankaflavin and monascin, as a reductive enzyme in the azaphilone polyketide pathway.

Delineating citrinin biosynthesis: Ctn-ORF3 dioxygenase-mediated multi-step methyl oxidation precedes a reduction-mediated pyran ring cyclization.

Citrinin (3) is a polyketide-derived mycotoxin, that is, produced by Monascus, Penicillium, and Aspergillus spp. and is a common contaminant in a number of agricultural products. ctPKS, a non-reducing type iterative polyketide synthase with a C-terminal reductive domain, is proposed to generate the polyketide backbone of 3. The targeted gene inactivation of ctn-orf1 or ctn-orf3 gene resulted in the accumulation of a benzaldehyde derivative 6, and the ectopic expression of ctPKS/ctnB in yeast produced 6, demonstrating that ctPKS generates 6 with the support of CtnB and suggesting that Ctn-ORF1/Ctn-ORF3 converts 6 into 3. The Δctn-orf1 mutant also produced a novel benzdialdehyde derivative 10. When either 6 or 10 was fed into a ΔctPKS mutant, 3 was readily detected, which confirms that both 6 and 10 are involved in the biosynthesis of 3. A bioconversion experiment of 6 in the ectopic expression system demonstrated that ctn-orf3 expression, but not ctn-orf1 expression, efficiently consumed 6. The resulting metabolite(s) of 6 could not be identified, however. A recombinant Ctn-ORF3 enzyme was demonstrated to convert 6 into 10 and a hypothetical carboxylic derivative 8, which substantiates that Ctn-ORF3 oxidizes the exocyclic methyl moiety of 6. Ctn-ORF1 is thus proposed to reduce 8 and the subsequent non-enzymatic reactions to complete the biosynthesis of 3. The present study delineates the biosynthetic route of 3, proposing the biochemical mechanism, that is, involved in producing the natural dihydropyranoquinone structure.

A single module type I polyketide synthase directs de novo macrolactone biogenesis during galbonolide biosynthesis in Streptomyces galbus.

Galbonolide (GAL) A and B are antifungal macrolactone polyketides produced by Streptomyces galbus. During their polyketide chain assembly, GAL-A and -B incorporate methoxymalonate and methylmalonate, respectively, in the fourth chain extension step. The methoxymalonyl-acyl carrier protein biosynthesis locus (galG to K) is specifically involved in GAL-A biosynthesis, and this locus is neighbored by a gene cluster composed of galA-E. GalA-C constitute a single module, highly reducing type I polyketide synthase (PKS). GalD and GalE are cytochrome P450 and Rieske domain protein, respectively. Gene knock-out experiments verified that galB, -C, and -D are essential for GAL biosynthesis. A galD mutant accumulated a GAL-C that lacked two hydroxyl groups and a double bond when compared with GAL-B. A [U-(13)C]propionate feeding experiment indicated that no rare precursor other than methoxymalonate was incorporated during GAL biogenesis. A search of the S. galbus genome for a modular type I PKS system, the type that was expected to direct GAL biosynthesis, resulted in the identification of only one modular type I PKS gene cluster. Homology analysis indicated that this PKS gene cluster is the locus for vicenistatin biosynthesis. This cluster was previously reported in Streptomyces halstedii. A gene deletion of the vinP2 ortholog clearly demonstrated that this modular type I PKS system is not involved in GAL biosynthesis. Therefore, we propose that GalA-C direct macrolactone polyketide formation for GAL. Our studies provide a glimpse into a novel biochemical strategy used for polyketide synthesis; that is, the iterative assembly of propionates with highly programmed ß-keto group modifications.

The Differential Developmental Neurotoxicity of Valproic Acid on Anterior and Posterior Neural Induction of Human Pluripotent Stem Cells.

Valproic acid (VPA), widely used as an antiepileptic drug, exhibits developmental neurotoxicity when exposure occurs during early or late pregnancy, resulting in various conditions ranging from neural tube defects to autism spectrum disorders. However, toxicity during the very early stages of neural development has not been addressed. Therefore, we investigated the effects of VPA in a model where human pluripotent stem cells differentiate into anterior or posterior neural tissues. Exposure to VPA during the induction of neural stem cells induced different developmental toxic effects in a dose-dependent manner. For instance, VPA induced cell death more profoundly during anteriorly guided neural progenitor induction, while inhibition of cell proliferation and enhanced differentiation were observed during posteriorly guided neural induction. Furthermore, acute exposure to VPA during the posterior induction step also retarded the subsequent neurulation-like tube morphogenesis process in neural organoid culture. These results suggest that VPA exposure during very early embryonic development might exhibit cytotoxicity and subsequently disrupt neural differentiation and morphogenesis processes.

Guidelines for Manufacturing and Application of Organoids: Brain.

This study offers a comprehensive overview of brain organoids for researchers. It combines expert opinions with technical summaries on organoid definitions, characteristics, culture methods, and quality control. This approach aims to enhance the utilization of brain organoids in research. Brain organoids, as three-dimensional human cell models mimicking the nervous system, hold immense promise for studying the human brain. They offer advantages over traditional methods, replicating anatomical structures, physiological features, and complex neuronal networks. Additionally, brain organoids can model nervous system development and interactions between cell types and the microenvironment. By providing a foundation for utilizing the most human-relevant tissue models, this work empowers researchers to overcome limitations of two-dimensional cultures and conduct advanced disease modeling research.

Transcriptional Signature of Valproic Acid-Induced Neural Tube Defects in Human Spinal Cord Organoids.

In vertebrates, the entire central nervous system is derived from the neural tube, which is formed through a conserved early developmental morphogenetic process called neurulation. Although the perturbations in neurulation caused by genetic or environmental factors lead to neural tube defects (NTDs), the most common congenital malformation and the precise molecular pathological cascades mediating NTDs are not well understood. Recently, we have developed human spinal cord organoids (hSCOs) that recapitulate some aspects of human neurulation and observed that valproic acid (VPA) could cause neurulation defects in an organoid model. In this study, we identified and verified the significant changes in cell-cell junctional genes/proteins in VPA-treated organoids using transcriptomic and immunostaining analysis. Furthermore, VPA-treated mouse embryos exhibited impaired gene expression and NTD phenotypes, similar to those observed in the hSCO model. Collectively, our data demonstrate that hSCOs provide a valuable biological resource for dissecting the molecular pathways underlying the currently unknown human neurulation process using destructive biological analysis tools.

Time-efficient implantable catheters for draining malignant ascites in terminal cancer patients.

BACKGROUND: There is a need for an improved version of the implantable catheter for malignant ascites in the abdominal cavity. OBJECTIVE: New implantable catheters have been developed that drain ascites from the abdominal cavity to the bladder by applying pressure. Based on pigtail catheters, these newly designed catheters have silicone membranes and apertures. METHODS: Experimental instruments controlled flow rates and water level to observe changes of the activation pressure and its cycle time along flow rates and turns of catheters. Furthermore, various normality tests, difference tests and non-parametric tests were investigated to observe statistical validity. RESULTS: Cycle times were significantly affected by flow rate (3/4 cases of p< 0.05). The effects of flow rate on activation pressure, however, were not significant (1/4 case of p< 0.05). Cycle times were not significantly affected by the number of turns of the catheter (3/8 cases of p< 0.05). In contrast, the effects of the turns on activation pressure were significant (5/8 cases of p< 0.05). CONCLUSION: Overall, there was no significant difference between cycle times for 1.5 turns and 2.0 turns of catheters. In addition, catheters with 1.5 turns have a lower activation pressure than catheters with 2.0 turns. It is possible to customize catheters based on the ascites excretion and urination rates of various terminal patients.

The effects of hemodialysis on the functional brain connectivity in patients with end-stage renal disease with functional near-infrared spectroscopy.

This study aimed to investigate functional brain connectivity in patients with end-stage renal disease (ESRD) undergoing hemodialysis using functional near-infrared spectroscopy (fNIRS) and to analyze the effect of hemodialysis on functional brain connectivity. We prospectively enrolled patients with ESRD undergoing hemodialysis for > 6 months without any history of neurological or psychiatric disorders. fNIRS data were acquired using a NIRSIT Lite device. Measurements were performed thrice in the resting state for each patient: before the start of hemodialysis (pre-HD), 1 h after the start of hemodialysis (mid-HD), and after the end of hemodialysis (post-HD). We processed and exported all data, and created a weighted connectivity matrix using Pearson correlation analysis. We obtained functional connectivity measures from the connectivity matrix by applying a graph theoretical analysis. We then compared differences in functional connectivity measures according to hemodialysis status in patients with ESRD. We included 34 patients with ESRD. There were significant changes in the mean clustering coefficient, transitivity, and assortative coefficient between the pre- and post-HD periods (0.353 vs. 0.399, p = 0.047; 0.523 vs. 0.600, p = 0.042; and 0.043 vs. - 0.012, p = 0.044, respectively). However, there were no changes in the mean clustering coefficient, transitivity, and assortative coefficient between the pre- and mid-HD periods, or between the mid- and post-HD periods. In addition, there were no significant differences in the average strength, global efficiency, and local efficiency among the pre-, mid-, and post-HD periods. We demonstrated a significant effect of hemodialysis on functional brain connectivity in patients with ESRD. Functional brain connectivity changes more efficiently during hemodialysis.

The effects of the dialysis on the white matter tracts in patients with end-stage renal disease using differential tractography study.

This study aimed to determine whether white matter tracts correlate with kidney function using correlation tractography, and to investigate the effects of dialysis on white matter tracts in patients with end-stage renal disease (ESRD) using differential tractography. Ten patients with ESRD, who had a glomerular filtration rate of < 15 mL/min/1.73 m2, were enrolled in this prospective study. Diffusion tensor imaging (DTI) was performed both before and after dialysis. We discovered that white matter tracts correlated with the estimated glomerular filtration rate based on pre- and post-dialysis DTI using correlation tractography and investigated the differences in the white matter tracts between pre- and post-dialysis DTI in patients with ESRD using differential tractography. Correlation tractography revealed no quantitative anisotropy of the white matter tracts that correlated with the estimated glomerular filtration rate in pre- and post-dialysis patients with ESRD. Differential tractography revealed significant differences in several white matter tracts, particularly the cingulum, thalamic radiation, corpus callosum, and superior longitudinal fasciculus, between pre- and post-dialysis DTI, which revealed increased diffusion density after dialysis. We demonstrated the significant effects of dialysis on several white matter tracts in patients with ESRD using differential tractography, which showed increased diffusion density after dialysis. In this study, we confirmed the effects of dialysis on brain structure, especially white matter tracts.

Intrinsic prefrontal functional connectivity according to cognitive impairment in patients with end-stage renal disease.

Background: This study aimed to investigate differences in intrinsic prefrontal functional connectivity according to the presence of cognitive impairment in patients with end-stage renal disease (ESRD) using functional near-infrared spectroscopy (fNIRS). Methods: We prospectively enrolled 37 patients with ESRD who had been undergoing hemodialysis for more than 6 months and had no history of neurological or psychiatric disorders. All patients with ESRD underwent the Korean version of the Montreal Cognitive Assessment (MoCA-K) to assess cognitive function. The NIRSIT Lite device (OBELAB Inc.) was used to acquire fNIRS data, and the NIRSIT Lite Analysis Tool program was used to process the data and generate a functional connectivity matrix. We obtained functional connectivity measures by applying graph theory to the connectivity matrix using the BRAPH (brain analysis using graph theory) program. Results: Of the 37 patients with ESRD, 23 had cognitive impairment, whereas 14 patients showed no cognitive impairment. Intrinsic prefrontal functional connectivity was significantly different between groups. Network measures of strength, global efficiency, and mean clustering coefficient were lower in ESRD patients with cognitive impairment than in those without cognitive impairment (4.458 vs. 5.129, p = 0.02; 0.397 vs. 0.437, p = 0.03; and 0.316 vs. 0.421, p = 0.003; respectively). There were no significant correlations between MoCA-K scores and clinical characteristics. Conclusion: We demonstrated a significant association between cognitive function and intrinsic prefrontal functional connectivity in patients with ESRD. ESRD patients with cognitive impairment have reduced connectivity and segregation in the prefrontal brain network compared to those without cognitive impairment.

Humoral response to vaccination against SARS-CoV-2 in patients undergoing dialysis.

Patients undergoing maintenance dialysis have a higher mortality rate associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and response rates to vaccination against SARS-CoV-2 vary from 29.6% to 96.4% in such patients. This study aimed to assess the immunogenicity of SARS-CoV-2 vaccination in Korean patients undergoing dialysis. We enrolled 70 SARS-CoV-2-vaccinated patients undergoing dialysis, with 11 healthcare workers serving as healthy control subjects. Thirty-two patients had received a third vaccination, whereas 38 had received 2 vaccinations. The healthy control subjects completed the second vaccination. Immunoglobulin G (IgG) antibodies targeting the receptor-binding domain of the S1 subunit of the SARS-CoV-2 spike protein were measured The vaccination responder rates were 86% (37/43), 96% (26/27), and 91% (10/11) in the patients undergoing hemodialysis and peritoneal dialysis and healthy controls, respectively. IgG antibody levels were significantly higher when a third dose was administered, independent of the type of vaccine or the time interval between vaccination and the subsequent blood sampling date. When a third dose of vaccine was administered, there was no difference in IgG antibody levels between those receiving cross-vaccination or a single vaccine. There was no significant difference in IgG antibodies between healthy controls and patients undergoing dialysis. Patients on dialysis exhibited a sufficient antibody-related response to vaccination against SARS-CoV-2, even in those receiving cross-vaccination, and the antibody titer was higher after a third vaccination. Therefore, it is necessary to administer a third vaccine dose to Korean patients undergoing dialysis.

Microfluidic electrode array chip for electrical stimulation-mediated axonal regeneration.

The precise manipulation of the neural stem cell (NSC)-derived neural differentiation is still challenging, and there is a technological barrier to regulate the axonal regeneration in a controlled manner. Here, we developed a microfluidic chip integrated with a microelectrode array as an axonal guidance platform. The microfluidic electrode array chip consisted of two compartments and a bridge microchannel that could isolate and guide the axons. We demonstrated that the NSCs were largely differentiated into neural cells as the electric field was applied to the microfluidic electrode array chip. We also confirmed the synergistic effects of the electrical stimulation (ES) and neurotrophic factor (NF) on axonal outgrowth. This microfluidic electrode array chip can serve as a central nervous system (CNS) model for axonal injury and regeneration. Therefore, it could be a potentially powerful tool for an in vitro model of the axonal regeneration.

Cell-line dependency in cerebral organoid induction: cautionary observations in Alzheimer's disease patient-derived induced pluripotent stem cells.

The cerebral organoid (CO) model has been used in the study of various neurodegenerative diseases owing to its physiological implications. However, the CO model may only be representative of certain clinical findings in affected patients, while some features are not recapitulated. In this study, we found that neurons in the CO model from patients with Alzheimer's disease were less responsive to depolarization, in contrast to previous reports. This difference may be partly attributed to the variations in brain spatial identity depending on the genetic background of the induced pluripotent stem cells. Our current observation raises concerns that the phenotypes observed in the CO model need to be carefully evaluated for their clinical implications.

Glymphatic system dysfunction in patients with early chronic kidney disease.

Introduction: It 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. Methods: In 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. Results: Eighteen 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. Conclusion: We 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.