Overview

This was a prospective, randomized, multicenter clinical trial. Seventy-eight patients with primary membranous nephropathy (PMN) were randomly divided into intervention or control group. Intervention group was given rituximab combined with corticosteroids in induction therapy and the control group was given rituximab monotherapy. After 6 months, patients who had decreased 24h urinary protein by > 25% but did not achieve CR were given rituximab maintenance therapy. The complete response rate at 12 months was measured.

Eligibility

Inclusion Criteria

1. Men and women aged 18-75 years;
2. Patients diagnosed as primary membranous nephropathy (PMN) by renal biopsy;
3. After treatment with ACE inhibitors or ARBs for at least 3 months, the following two points were met (unless intolerance to ACE inhibitors or ARBs, contraindications, hypotension that may cause side effects, or the investigator judged that the patient was not suitable for RAS inhibitors):

        (1) Those who have an average 24-hour urine protein ≥ 3.5g twice a week, or an average
        24-hour urine protein ≥ 5g twice in 14 days, the requirement of RASi for at least 3 months
        is not required (2) Blood pressure≤ 130/80mmHg, 4. Glomerular filtration rate (eGFR)
        ≥30mL/min/1.73m2 (calculated according to the CKD-EPI formula) 5. If female, must be
        postmenopausal or postoperatively infertile or on medical contraception (considering the
        potential risk of thromboembolism in patients with kidney disease); 6. Subjects voluntarily
        signed the informed consent form;
        Exclusion Criteria:
          1. Patients with type 1 diabetes mellitus or type 2 diabetes mellitus complicated with
             diabetic nephropathy. Patients with a recent history of steroid-induced diabetes were
             eligible if renal biopsies show no evidence of secondary diabetic nephropathy within 6
             months before the screening period
          2. Patients with secondary membranous nephropathy (such as hepatitis B and C, systemic
             lupus erythematosus, drug therapy, malignant tumors and other secondary causes);
          3. Previous treatment with rituximab, steroids, alkylating agents, calcineurin
             inhibitors, synthetic ACTH, mycophenolate (MMF), and azathioprine;
          4. Receipt of any other study medication (within the last month);
          5. Suspected or known allergy or immune reaction to rituximab, corticosteroids or any of
             their components (including excipients);
          6. Active infection, such as active hepatitis B or hepatitis C, tuberculosis (evidence of
             active tuberculosis infection within 1 year), or human immunodeficiency virus HIV
             infection (positive for anti-HIV antibodies), etc.
          7. A history of immunodeficiency, including other acquired or congenital immunodeficiency
             diseases, or organ transplantation;
          8. Females with a positive pregnancy screening test or lactating or planning to become
             pregnant in the next 24 months. Female or male patients who were unwilling to use
             contraceptive methods throughout the study;
          9. A history of mental illness;
         10. Laboratory tests that meet the following criteria need to be excluded:
        (1) Hemoglobin<80g/L; (2) Platelet < 80×109/L; (3) Neutrophil <1.0×109/L; (4) Aspartate
        aminotransferase (AST) or amino aminotransferase (ALT) > 2.5× upper limit of normal except
        in relation to the primary disease; 11. Very high-risk patients: presenting with
        life-threatening nephrotic syndrome, or unexplained rapid deterioration of renal function
        12. Any patient judged by the investigator to be unsuitable for inclusion in the trial.