Randomized, open label, multicentre (20 sites), prospective trial comparing the efficacy of two therapeutic strategies to obtain clinical remission 1 year after diagnosis of Idiopathic Membranous Nephropathy with nephrotic syndrome and anti-PLA2R1 (phospholipase A2 receptor 1) antibodies:

• GEMRITUX protocol: 6 months of symptomatic antihypertensive and antiproteinuric therapy, and if the nephrotic syndrome persists at month-6 (urinary protein/creatinine ratio (UPCR) remains > 3.5 g/g and albuminemia < 30 g/l), two 375 mg/m2 rituximab infusions at 1-week interval.

• Personalized treatment:

  • restricted anti-CysR activity at inclusion : 6-month symptomatic antihypertensive and antiproteinuric treatment (KDIGO)
  • restricted anti-CysR activity after 6 months of symptomatic treatment with persisting nephrotic syndrome (UPCR remains > 3.5 g/g and albuminemia < 30 g/l): two 375 mg/m2 rituximab infusions at 1-week interval;
  • Anti-CTLD (C-type lectin domains ) 1/7 activity at inclusion or after 6 months with persisting nephrotic syndrome (UPCR remains > 3.5 g/g and albuminemia < 30 g/l): two 1g rituximab infusions at 2-week interval at month 0 and/or month 6.

Inclusion Criteria:

• Age 18 years or more
• Anti-PLA2R1 activity detected by ELISA or Euroimmune Immunofluorescence Assay
• Nephrotic syndrome defined by proteinuria > 3.5 g/24h (or UPCR > 3.5 g/g) and serum albumin < 30 g/L at diagnosis
• eGFR (CKD-EPI) > 30 ml/min/1,73 m2 at diagnosis
• Symptomatic treatment according to KDIGO guidelines: maximal tolerated dose of NIAT : Non Immunosuppressive Antiproteinuric Treatment (angiotensin-converting enzyme inhibitor and/or angiotensin 2 receptor blockers, diuretics and statins)
• Medical insurance
• Signed informed consent
• Having understood and accepted the need for long-term medical follow-up
• Woman of child-bearing age must be using an effective method of contraception

Exclusion Criteria:

• Secondary Membranous Nephropathy: Membranous Nephropathy related to cancer, infectious, systemic lupus erythematosis, drug
• Anti-PLA2R1 antibodies not confirmed by central analysis (in this case the patient will be replaced)
• Pregnancy or breastfeeding
• Immunosuppressive treatment in the 3 last months
• Cancer under treatment
• Patient with complicated nephrotic syndrome that would require early immunosuppressive treatment (thrombosis, acute renal failure…)
• Patients with active, severe infections or active hepatitis B
• Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients
• Patients in a severely immunocompromised state
• Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
• Patients unable to give an informed consent