Assess the Efficacy and Safety of Multi-target Therapy in Lupus Nephritis

• To assess the efficacy of FK506 combined with MMF vs intravenous cyclophosphamide (CTX) pulses in treatment of class Ⅲ,Ⅳ,Ⅴ,Ⅲ+Ⅴand Ⅳ+Ⅴ Lupus Nephritis (LN).
• To investigate the safety and tolerability of FK506 combined with MMF vs intravenous CTX pulses in the treatment of class Ⅲ,Ⅳ,Ⅴ,Ⅲ+Ⅴand Ⅳ+Ⅴ LN.

Inclusion criteria

• Written informed consent by subject or guardian
• 18 to 65 years of age (inclusive 18 and 65), male or female
• Diagnosis of SLE according to the American College of Rheumatology criteria (1997)
• Diagnosis of Class Ⅲ,Ⅳ,Ⅴ,Ⅲ+Ⅴand Ⅳ+ⅤLN according to the ISN/RPS 2003 classification by light, immunofluorescence, and electron microscopy within 6 months before enrollment
• Pathologic chronic index (CI) ≤3' without thrombotic microangiopathy (TMA)
• SLE Disease Activity Index (DAI) >10'
• Proteinuria ≥1.5g/d，with or without active urinary sediment
• Serum creatinine (Scr)≤3.0mg/dl (265.2 mol/L)

Exclusion criteria

• Previous treatment with MMF, CTX, tacrolimus, Cyclosporin A (CsA), large doses of immunoglobulin and methylprednisolone (MP), plasmapheresis or renal replacement therapy within the past 12 weeks. Oral glucocorticoids, azathioprine, intravenous MP (≤80mg/d)， short-time CsA (<2 weeks) or leflunomide (<4 weeks) are allowed
• ALT or AST increase twice above the upper limit of the normal range
• Hyperglycemia is defined as fasting blood glucose level ≥7.0 mmol/L and/or postprandial blood sugar level>11.1 mmol/L
• Known hypersensitivity or contraindication to any components of MMF, tacrolimus, CTX or glucocorticoids
• History of present illness:

• active HBV infection (HBsAg, HBeAg and anti-HBc positive or HBsAg, anti- HBe and anti-HBc positive), HCV infection, pulmonary tuberculosis, cytomegalovirus(CMV) infection (defined as CMV-IgM positive or CMV-DNA positive), fungal infection or HIV infection, within 3 months before the enrollment
• non-healed active peptic ulcer within 3 months before the enrollment
• drug or drinking abuse
• malnutrition (BMI <18.5kg/m2) or body weight <50Kg
• Other active diseases, such as:

• severe cardiovascular diseases
• chronic obstructive pulmonary disease(COPD)or asthma requiring oral glucocorticoids
• marrow depression not due to SLE activation: white blood cell count <3000/mm3 or neutrophil count <1300/mm3 or platelet count <50000/mm3
• Severe infection or need of antibiotic therapy
• Female patients who are pregnant/breastfeeding or those patients (both gender) who refused contraception
• Life-threatening complications such as large hydropericardium, pneumohemorrhagia, lupus encephalopathy and severe pulmonary hypertension or patients in need of MP pulse (>0.5g/d ) treatment because of aggravation of SLE
• Known to be non-compliance or violation of the protocol base on investigator's judgement
• Patient who participate of any other investigational drug study.