MIMIGA Study
Title:
Modification of Intestinal Microbiome in Patients with Primary IgA Nephropathy (IgAN)
Objective:
To evaluate whether supplementation with short-chain fatty acids (SCFAs)-specifically sodium butyrate-can reduce proteinuria and slow the progression of chronic kidney disease (CKD) in patients with IgAN by modulating the gut microbiome.
Study Design:
Type: Randomized, double-blind, placebo-controlled, crossover clinical trial.
Participants: Adults with biopsy-proven IgA nephropathy and matched healthy controls.
Phases:
Treatment Period 1: 12 weeks of SCFA or placebo.
Washout Period: 12 weeks.
Treatment Period 2: Crossover-those who received SCFA get placebo and vice versa for 24 weeks.
Follow-up: 4-8 weeks post-treatment.
Primary Endpoint:
≥25% reduction in proteinuria (urinary protein-creatinine ratio) from baseline at week 12 and 24.
Secondary and Exploratory Endpoints:
Changes in:
eGFR (kidney function)
Inflammatory cytokines (IL-1, IL-6, IL-10, TNF-α)
Gut microbiome composition (via 16S rRNA sequencing)
Progression to CKD stage 4
Systolic blood pressure
Serum lipids
Quality of life (KDQOL-36 questionnaire)
Safety Monitoring:
Adverse events, especially gastrointestinal issues.
Blood and urine biochemistry.
Clinical symptoms and patient-reported outcomes.
Eligibility Criteria:
Inclusion: Adults with IgAN, stable on RAS inhibitors, eGFR ≥ 30 ml/min/1.73 m².
Exclusion: Diabetes, other kidney or autoimmune diseases, recent use of immunosuppressants or antibiotics, uncontrolled hypertension, liver disease, pregnancy.
Microbiome Analysis:
DNA from stool samples analyzed using next-generation sequencing (NGS) targeting the V3-V4 regions of the 16S rRNA gene.
Expected Impact:
Provide first clinical evidence for SCFA as a safe, cost-effective therapy to slow CKD progression in IgAN.
Open new research directions for gut microbiome-targeted treatments in nephrology and other fields (e.g., diabetes, immunology).