Trial of Belimumab Combined With Multi-target Induction Therapy in Lupus Nephritis

Inclusion Criteria:

• Active LN in accordance with the American College of Rheumatology (ACR) diagnosticcriteria for SLE (1997), SLE-DAI>10 points (except type Ⅴ LN).
• Patients with active lupus nephritis (type Ⅲ, Ⅳ, Ⅴ, Ⅴ+Ⅲ, Ⅴ+Ⅳ) diagnosed by lightmicroscopy, immunofluorescence microscopy, and electron microscopy according to theISN/RPS2003 lupus nephritis classification criteria, with pathological chronicityindex (CI) less than 3 points and no TMA like changes in interstitial vessels.
• Proteinuria ≥1.5g/24h, with or without active urinary sediment (urinary sediment redblood cell count >100/ul, or white blood cell count >5 /HP, or red blood cell cast,excluding urinary tract infection).
• Serum creatinine <3.0mg/dL or eGFR<30 ml/min/1.73m^2 (CKD-EPI formula).
• Received methylprednisolone pulse therapy within 2 weeks before enrollment, cumulativedose 1.5-3.0g).

Exclusion Criteria:

• Required renal replacement therapy or received renal replacement therapy within 3months.
• Abnormal liver function with elevated ALT, AST or bilirubin more than 2 times theupper limit of normal.
• Abnormal glucose metabolism, defined as fasting blood glucose concentration ≥7.0mmol/Land/or 2-hour postprandial blood glucose concentration >11.1mmol/L.
• Mycophenolate mofetil, cyclophosphamide, tacrolimus, cyclosporine A, and high-doseintravenous immunoglobulin (IVIG) were used in the past 12 weeks; It did not includeoral hormones, azathioprine or tripterygium wilfordii polyglycosides, or intravenouslow-dose MP (less than 80mg/ day), or short-term use of cyclosporine A<2 weeks, orleflunomide <4 weeks.
• Known allergy to or contraindication to MMF, tacrolimus, or belimumab; Patients withactive infection or intravenous antibiotic use within 1 month before admission.
• Current or past 3 months: active hepatitis B, hepatitis C, tuberculosis,cytomegalovirus pneumonia, active fungal infection, syphilis infection or HIVinfection, etc.; Active peptic ulcer; A history of drug use and alcohol abuse; Severemalnutrition (BMI<16 kg/m^2).
• Other active diseases, such as severe life-threatening cardiovascular diseases;Chronic obstructive pulmonary disease, or asthma requiring treatment with oralsteroids; Bone marrow suppression caused by SLE activity was excluded: WBC<3000/ul,absolute neutrophil count <1300/ul, and platelet count < 50 000/ul. Patients withactive SLE who received double plasma filtration, plasma exchange or high-dose gammaglobulin therapy within 4 weeks.
• Patients with malignant hypertension.
• Women who have fertility requirements, refuse contraception or are lactating.
• Other investigators considered that they were not suitable for enrollment and may haverapid disease progression or severe disease complications.