Impact of Dapagliflozin for the Regulation of Immunological Activity in Membranous Nephropathy

Inclusion criteria

• Participants ≥ 18 years old and < 85 years old;
• Membranous Nephropathy associated with anti-PLA2R1 autoantibodies;
• Urine Protein Creatinine Ratio (UPCR) between 0.5 g/g and 3.5 g/g;
• Immunological relapse defined by an increase in anti-PLA2R1 antibody concentration > 14 RU/mL after a phase of anti-PLA2R1 antibody negativation, (i.e. immunological remission) and complete or partial clinical remission;
• Antiproteinuric treatment at maximal and stable dose. According to KDIGO 2024 guidelines on management of glomerular diseases and the French recommendations (PNDS GEM 2022), symptomatic treatment of membranous nephropathy should include: (i) a low sodium diet, (ii) a diuretic and (iii) an angiotensin-converting enzyme inhibitor or an angiotensin 2 receptor blocker at maximal tolerated dose (i.e., absence of orthostatic hypotension and no increase in serum creatinine >30%).

Exclusion criteria

• Immunosuppressive treatment for MN in the 6 months prior to the selection visit;
• Secondary MN (associated with cancer, infectious disease, autoimmune or iatrogenic disease);
• Active nephrotic syndrome defined according to KDIGO guidelines as proteinuria > 3.5 g/day (or 3.5 g/g in a urine sample) and albumin < 30 g/L;
• No previous history of immunological remission (anti-PLA2R1 antibodies < 14 RU/mL in ELISA or negative indirect immunofluorescence) or clinical remission (partial or complete);
• Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption disorders
• Patients at risk for ketoacidosis including patients with a low reserve of functional beta cells (e.g. patients with type 2 diabetes with low C-peptide or latent autoimmune diabetes mellitus or patients with a history of pancreatitis or patients who are receiving insulin treatment), patients with conditions leading to reduced food intake or severe dehydration, patients with low insulin reserve, and patients with increased insulin requirements due to acute medical illness, surgery or excessive alcohol consumption;
• Type 1 diabetes;
• Pregnancy or breastfeeding;
• Estimated CKD-EPI Glomerular Filtration Rate (eGFR) < 25 ml/min/1.73m2;
• Severe liver failure (Child-Pugh stage C);
• NYHA functional class IV heart failure;
• Patients already currently receiving dapagliflozin or another SGLT2 inhibitor for another condition;
• Repeated urinary tract infections;
• Hypersensitivity to the active substance or excipients.