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IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Its progression is often accompanied by cognitive decline, manifesting as multi-dimensional cognitive deficits in areas such as memory, attention, and executive function. Cognitive decline in patients with IgAN severely impacts their quality of life, yet the underlying central nervous system (CNS) damage mechanisms remain unclear, and no effective interventions are currently available. Recent domestic and international studies suggest a potential interactive damage network involving the brain, gut microbiota, and kidneys in patients with chronic kidney disease (CKD). Therefore, exploring the causes of cognitive decline in IgAN patients from the perspective of multi-organ interactive damage, identifying brain injury targets and aberrant gut microbial communities that correlate with changes in renal function, is crucial for the development of effective and precise clinical interventions.
Our team has been conducting MRI research on brain injury associated with cognitive decline in CKD since 2015. We have extensive experience in studying brain structure, function, metabolism, and perfusion in patients with end-stage renal disease (ESRD). Our work has been supported by numerous grants, including the General Program and Young Scientists Fund of the National Natural Science Foundation of China (NSFC) and the Key R&D Program of Shaanxi Province, yielding a series of scientific achievements. The etiological heterogeneity and high prevalence of IgAN suggest that we should focus on the central mechanisms of cognitive decline in this specific patient population. The recent clinical application of 7.0 Tesla (T) ultra-high field MRI provides critical hardware support, enabling us to investigate sub-millimeter-level structural and functional abnormalities in the early stages of IgAN.
This study aims to recruit 100 patients with IgAN from the Department of Nephrology and 100 demographically matched healthy controls from the local community. We will collect serum, stool samples, and brain ultra-high field MRI data from both patients and controls. By integrating these data with assessments from multi-dimensional neurocognitive scales, we will explore the potential brain-gut-kidney damage characteristics underlying cognitive decline in IgAN patients from the perspectives of serum metabolomics, fecal gut microbiota analysis, and multi-modal ultra-high field brain MRI analysis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IgAN | |||
| HC |
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| Measure | Description | Time Frame |
|---|---|---|
| Gut Microbiome Metagenomic Characteristics | Description: Taxonomic composition, relative abundance of microbial taxa, alpha diversity indices (Shannon, Simpson), and functional pathway profiles derived from shotgun metagenomic sequencing of fecal samples. Unit/Scale: Relative abundance (%), Shannon index, Simpson index, normalized pathway abundance. | April 2025 to March 2027 |
| Functional Neuroimaging Indices | Description: Resting-state functional magnetic resonance imaging (rs-fMRI) derived metrics, including functional connectivity (FC), amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo). Unit/Scale: Standardized Z-scores, correlation coefficients. | April 2025 to March 2027 |
| Cognitive Function Scores | Description: Cognitive performance assessed using the Montreal Cognitive Assessment (MoCA). Scale/Range: 0-30 points. Interpretation: Higher scores indicate better cognitive function; lower scores indicate more severe cognitive impairment. | April 2025 to March 2027 |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Metabolomic and Biomarker Levels | Description: Quantitative analysis of serum metabolomic profiles, inflammatory factors (e.g., IL-6, TNF-α), and neurotransmitters (e.g., serotonin, dopamine) using targeted metabolomics assays. Unit/Scale: pg/mL, ng/mL, or standardized relative concentration units. | April 2025 to March 2027 |
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Inclusion Criteria:
Exclusion Criteria:
Contraindications for 7.0T MRI Presence of ferromagnetic implants in the body (e.g., cardiac pacemakers, defibrillators, neurostimulators, aneurysm clips, cochlear implants, or any other metallic foreign bodies).
Non-ferromagnetic implants (e.g., titanium alloy, orthopedic implants), intrauterine devices (IUDs), or non-removable dental prosthetics (including dental implants).
Metallic foreign bodies in the eye or body (e.g., metal fragments, shrapnel, or metallic debris), such as in individuals with a history of welding or metal-related injuries.
Tattoos or permanent makeup (e.g., on eyebrows or lips) acquired within the last month.
Claustrophobia. Fever. Inclusion Criteria for the Healthy Control Group
All healthy controls must meet the following criteria:
Exclusion Criteria for the Healthy Control Group
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IgA Nephropathy (IgAN) Group: A cohort of 100 patients diagnosed with IgA nephropathy, confirmed by pathological biopsy.
Healthy Control (HC) Group: A cohort of 100 healthy volunteers who are demographically matched to the patient group in terms of age, gender, and educational attainment.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Functional and Molecular Imaging Key Lab of Shaanxi Province, Department of Radiology, Tangdu Hospital, Fourth Military Medical University | Shanxi | Xi'an | 713800 | China |
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Stool/Fecal samples
| Fecal Gut Microbiome Analysis |
Description: Taxonomic composition, alpha/beta diversity, and differential microbial taxa identified via 16S rRNA gene sequencing or shotgun metagenomic sequencing of fecal samples. Unit/Scale: Relative abundance (%), Shannon index, Simpson index, Bray-Curtis dissimilarity. |
| April 2025 to March 2027 |
| Memory Function (Cognitive Subdomain) | Description: Verbal memory assessed using the Auditory Verbal Learning Test (AVLT). Scale/Range: 0-75 points (AVLT total recall score). Interpretation: Higher scores indicate better memory performance. | April 2025 to March 2027 |
| Attention and Executive Function (Cognitive Subdomains) | Description: Attention and executive function assessed using the Stroop Color-Word Test and Trail Making Test (TMT). Unit/Scale: Reaction time (seconds), completion time (seconds), number of errors. Interpretation: Shorter completion time and fewer errors indicate better attention and executive function. | April 2025 to March 2027 |
| ID | Term |
|---|---|
| D005922 | Glomerulonephritis, IGA |
| ID | Term |
|---|---|
| D005921 | Glomerulonephritis |
| D009393 | Nephritis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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