Prospective, Multicenter Study of the Efficacy and Tolerance of Tacrolimus on Refractory Nephrotic Syndrome (RNS)

Exploring the efficacy and safety of Tacrolimus on refractory nephrotic syndrome ; Acquiring the experience of Tacrolimus on the treatment of refractory nephrotic syndrome in Chinese patients.

Inclusion Criteria:

1. Subjects of either sex, 14-65 years of age;
2. Diagnosis of Nephrotic syndrome with hypoalbuminemia (<3.0g/dl) and heavy proteinuria (> 3.5g/24hr);
3. Provision of written informed consent by subject or guardian;
4. Refractory nephrotic syndrome:

Steroid resistant: Persistence of proteinuria despite prednisone therapy 1mg/kg/d for 16 weeks; Steroid dependent: NS recurs when steroid dosage decease.Twice within 6 months, and 3 times within 1 year.

Exclusion Criteria:

1. Inability or unwillingness to provide written informed consent ;
2. Known hypersensitivity or contraindication to tacrolimus, cyclophosphamide, azathioprine, corticosteroids;
3. Usage of immunosuppression therapy (MMF, CTX, CysA, MTX ect) for more than 1 week within 1 month prior to first randomization;
4. Pregnancy, nursing or use of a non-reliable method of contraception;
5. Continuous dialysis starting more than 2 weeks before randomization into the induction phase and/or continuous dialysis with an anticipated duration of more than 8 weeks;
6. Previous kidney transplant or planted transplant;
7. Scr > 4mg/dl (353umol/L);
8. Active hepatitis, with liver dysfunction;
9. Diagnosed DM;
10. Participation in another clinic trial and/or receipt of investigational drugs within 4 weeks prior to screening .