The MIMIGA Study is a Randomized, Double-blind, Placebo-controlled Crossover Trial Evaluating the Safety and Efficacy of SCFA vs. Placebo. Administered Orally Once Daily With Standard Care, it Aims to Prevent CKD Progression in Biopsy-proven IgA Nephropathy by Modulating the Gut Microbiome.

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).

Inclusion Criteria: * \- Subjects aged 18 and older at the time of signing the informed consent form (ICF) before initiating any study specific activities/procedures. * Biopsy-proven IgA nephropathy. * Receiving a maximally tolerated and stable dose of RAS inhibitor therapy (ACEi or ARB) for at least 12 weeks prior to screening. Investigator discretion should be used in determining maximally tolerated and stable dose. * eGFR of at least 30 ml/min/1.73 m2 at screening based on the CKD-EPI equation. * Willing and able to provide informed consent and comply with all study requirements. Inclusion Criteria for SGLT2i stable subjects * Receiving a stable dose of an SGLT2i for at least eight weeks prior to screening * Must have the spot morning urine protein-creatinine ratio \> 500 mg/g * Inclusion Criteria for Run-In Subjects * Must have the spot morning urine protein-creatinine ratio \> 850 mg/g at screening * Willing to participate in an 8-week run-in period with an SGLT2i Additional Inclusion Criteria for Run-in Subjects at the end of Run-In * Must have completed the 8-week run-in period on a stable and well-tolerated dose of an SGLT2i * Must have the spot morning urine protein-creatinine ratio \> 500 mg/g confirmed at the Week -1 Visit * Must have an eGFR of ≥ 30 ml/min/1.73 m2 based on the CKD-EPI equation at the Week -1 Visit * Receiving treatment with SGLT2i at a stable dose for at least eight weeks prior to screening. Exclusion Criteria: * current diagnosis with another chronic kidney disease, including diabetic kidney disease,secondary IgAN, type 1 or 2 diabetes mellitus * gastrointestinal diseases (such as IBD, peptic ulcers etc.), * another immunological or autoimmune disorders * alcohol abuse * psychiatric disease and inability to assess follow-up +history of kidney transplantation or another organ transplantation, * use of systemic immunosuppressant medications, such as steroids, in the past 3 months, use of ATB in the past three months * blood pressure above 150 mmHg systolic or 95 mmHg diastolic * clinically significant history of liver disease (aspartate transaminase \[AST\] or alanine ttransaminase \[ALT\] \>3x the upper limit of normal \[ULN\]; or total bilirubin \>2x ULN at time of enrolment) * For women - pregnancy, breastfeeding, or intent to become pregnant during the study * For men - intent to father a child or donate sperm during the study * If the patient has received any investigational agent or approved treatment for IgAN (other than a RAS inhibitor) within one month (or five half-lives of the agent, whichever is longer) prior to Screening, if the investigational agent is a cytotoxic or mmunosuppressive, then this washout period is six months