Efficacy and Safety of Tacrolimus Sustained-release Capsules in Induction Treatment in Refractory Lupus Nephritis

• The changes of proteinuria [ Time Frame: every 3 months up to 6 months ] [ Designated as safety issue: Yes ]
• SLEDAI scores [ Time Frame: every 3 months up to 6 months ] [ Designated as safety issue: Yes ]
  SLEDAI:Systemic Lupus Erythematosus Disease Activity Index (Bombardier et al, 1992).
• Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: every 3 months up to 6 months ] [ Designated as safety issue: Yes ]
  Adverse events, including infections, transient increases in serum creatinine, gastrointestinal complaints, liver function disorder and glucose intolerance, etc.
• The changes of renal function [ Time Frame: every 3 months up to 6 months ] [ Designated as safety issue: Yes ]
• Relapse [ Time Frame: every 3 months up to 6 months ] [ Designated as safety issue: Yes ]

• proteinuria, renal function, relapse. [ Time Frame: every 3 months ] [ Designated as safety issue: Yes ]
• SLEDAI scores [ Time Frame: every 3 months ] [ Designated as safety issue: Yes ]
  SLEDAI:Systemic Lupus Erythematosus Disease Activity Index (Bombardier et al, 1992).
• Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: every 3 months ] [ Designated as safety issue: Yes ]
  Adverse events, including infections, transient increases in serum creatinine, gastrointestinal complaints, liver function disorder and glucose intolerance, etc.

This a pilot study to evaluate the efficacy and safety of Tacrolimus Sustained-release Capsules (ADVAGRAF) treatment for the induction therapy of refractory lupus nephritis (LN).

Inclusion Criteria:

1. Subjects of either sex, 14-65 years of age;
2. Diagnosis of SLE according to the ACR criteria (1997);
3. Kidney biopsy within the 6 months prior to study with a histologic diagnosis (ISN/RPS 2003 classification of LN) class IV, V, V+ III, V+ IV;
4. Usage of intravenous pulse cyclophosphamide for more than 3 times or immunosuppression therapy (AZA, MMF, oral cyclophosphamide, ect) for more than 6 months;
5. proteinuria > 1g/24hr or Scr > 1.3 mg/dl or active urinary sediment (erythrocyte cast, > 5 WBC/high power field (hpf) (excluding infection), > 5 RBC/hpf);
6. Provision of written informed consent by subject or guardian

Exclusion Criteria:

1. Inability or unwillingness to provide written informed consent ;
2. Usage of immunosuppression therapy (MMF, CTX, CysA, MTX etc) for more than 1 week within 1 month or intravenous MP Pulse treatment prior to entry;
3. Scr > 4mg/dl (354umol/L);
4. Needing pulse intravenous MP or intravenous immunoglobulin;
5. Lupus encephalopathy;
6. Diagnosed DM; Malignant tumors (except fully cured basal cell carcinoma);
7. History of significant gastrointestinal disorders (e.g. active peptic ulcer disease or pancreatitis) within 3 month prior to enter this study;
8. Known hypersensitivity or contraindication to tacrolimus, corticosteroids
9. Any Active systemic infection or history of serious infection within one month of entry or known infection with HIV, hepatitis B, or hepatitis C;
10. Participation in another clinic trial and/or receipt of investigational drugs within 4 weeks prior to screening;
11. Pregnancy, nursing or use of a non-reliable method of contraception.