This prospective randomized control trial is undertaken to evaluate the safety and efficacy of anti-CD20 monoclonal antibody, rituximab, used as 1. monotherapy, 2. in combination with cyclophosphamide, in the treatment of proliferative lupus nephritis, as compared with standard immunosuppressive therapy with cyclophosphamide and azathioprine.

Twenty patients will be randomized into 3 treatment arms to receive:

• Rituximab of 1000 mg given 2 weeks apart. On day the of rituximab, and 'pulse' methylprednisolone 250mg IV be given followed by prednisolone 30mg/day from Day 2 to Day 5.
• A treatment dose rituximab of 1000mg given 2 weeks apart and 'pulse' methylprednisolone 250mg IV be given followed by prednisolone 30mg/day from Day 2 to Day 5, and 'pulse' cyclophosphamide 500mg/m2 at baseline and day 14.
• Sequential therapy with oral cyclophosphamide (50 to 100 mg/day) for 6 months followed by azathioprine (up to 2.5mg/kg/day) for maintenance up to 12 months. Oral prednisolone will be given at 0.5 mg/kg/day (up to 30 mg daily) for 4 weeks, tapered by 5 mg every 2 weeks thereafter until 5mg /day for the rest of the study period. All patients would be started on angiotensin converting enzyme inhibitors before commencement of the trial and to continue at the same dosage throughout the study period. Patients who are on antimalarial agents and statins at baseline will be allowed to continue.

Clinical examination and laboratory investigations will be performed at 0, 4, 8, 12, 24, 36 and 48 weeks from the time of treatment. At each visit, patients will be evaluated for clinical manifestation of SLE and side effects of therapy. Laboratory parameters measured included the complete blood cell count with differential and platelet counts, chemistries survey, urinalysis, and 24- hour urinary for protein excretion and creatinine clearance.

Inclusion Criteria:

• Age > 18 years
• Active proliferative lupus nephrites
• Biopsy confirmed active proliferative lupus nephritis within 3 months prior to enrollment
• Proteinuria >= 2g/day
• Active urinary sediments
• Activity index of >= 6
• Elevated anti-double-stranded(anti-dsDNA) level at baseline
• Agreement to practice birth control
• SLE according to the American College of Rheumatology Criteria
• Informed consent was obtained

Exclusion Criteria:

• Pre-existing renal failure
• History of cancer
• Human immunodeficiency virus infection
• Active hepatitis B or C infection
• Active tuberculosis
• Diabetes mellitus
• A ny other chronic disease
• Unwillingness to comply with the protocol