Exploring the Brain - Gut Microbiota - Kidney Interactive Damage Mechanisms Underlying Cognitive Decline in Patients With IgA Nephropathy Using Ultra-high Field Magnetic Resonance Imaging

Brain-Gut-Kidney Axis in IgA Nephropathy Cognitive Decline: An Ultra-High Field MRI Study

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.

Inclusion Criteria:

1. Right-handed individuals, age 18-60 years;
2. Diagnosis of IgA nephropathy confirmed by renal biopsy.

Exclusion Criteria:

1. Secondary IgA nephropathy, such as that associated with systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, hepatitis B or C infection, or drug-induced causes.
2. History of kidney transplantation, hemodialysis, or peritoneal dialysis.
3. Acute cerebrovascular event within the past 3 months; a history of severe traumatic brain injury, brain tumor, stroke, or encephalomalacia that has resulted in identifiable lesions or significant asymmetry of cranial anatomy.
4. Malignant tumors; a history of intestinal surgery; or irritable bowel syndrome (IBS).
5. Use of antibiotics, steroids, immunosuppressants, or microbiota-based preparations within the past month.
6. Inflammatory bowel disease (IBD); or the presence of symptoms such as diarrhea, abdominal pain, or IBS-like symptoms within the past two weeks.
7. History of alcohol dependence.
8. Current use of psychiatric medications, such as antidepressants or anxiolytics.
9. Loss of hearing or vision.
10. Pregnancy or lactation.
11. Current participation in another clinical trial.

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:

1. Right-handed, aged 18-60 years;
2. All physiological indicators within the normal range, with no signs of disease;
3. No family history of psychiatric or neurological disorders.

Exclusion Criteria for the Healthy Control Group

1. History of cranial surgery, brain tumor, traumatic brain injury, stroke, or encephalomalacia resulting in significant asymmetry of cranial anatomy;
2. History of psychiatric disorders, alcohol dependence, or central nervous system diseases;
3. Presence of metallic foreign bodies in the body or claustrophobia, making them unsuitable for MRI scanning;
4. History of hypertension, diabetes, or hyperlipidemia;
5. Hearing or vision impairment that would affect communication during the MRI scan or the completion of cognitive assessments.