Please select the eligibility criteria that correspond to the clinical trial below.
Title: Comparison of Intravenous Low Dose Versus High Dose Cyclophosphamide as Induction Therapy in the Treatment of Proliferative Lupus Nephritis
Brief Summary: This study will be conducted to find out whether low dose or high dose cyclophosphamide therapy is effective in the treatment of proliferative lupus nephritis.It will also compare the side effects and risks of infection in low dose and high dose cyclophosphamide group. Half of the participants will receive a low dose cyclophosphamide for 3 months and half will receive high dose cyclophosphamide therapy monthly for 6 months followed by azathioprine 2 mg/kg.


Options:
A: Inclusion Criteria

* Diagnosed with SLE
* Historical evidence of SLE renal disease
* Elevated levels of dsDNA antibodies
* Weight of 40 kg or greater

Exclusion Criteria

* Active SLE renal disease
* Use of certain anti-inflammatory or cytotoxic therapies or therapeutic interventions during the months immediately before dosing
* Clinical laboratory test values outside of certain limits
* Malignant disease or immunodeficiency syndrome
* Acute or chronic infections
* History of serious heart disease
B: Inclusion Criteria:

1. A diagnosis of SLE according to the American College of Rheumatology (ACR) criteria
2. Age \>16 years
3. Proteinuria ≥500 mg in 24 hours/ urine routine microscopy showing active cellular casts/sediments.
4. Biopsy-proven proliferative lupus glomerulonephritis of class III, IV according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria.

Exclusion Criteria:

1. Patients ever treated previously with intravenous or oral cyclophosphamide or received steroids \>15mg/day in the last 3 months.
2. Patients with renal thrombotic microangiopathy, preexisting chronic renal failure, pregnancy, previous malignancy (except skin and cervical intraepithelial neoplasia), diabetes mellitus or coronary heart disease.
3. Patients with previously documented severe toxicity to immunosuppressive drugs.
4. Patients with acute/chronic infections.
5. Pregnancy
C: Inclusion Criteria:

* Diagnosis of Systemic lupus erythematosus (SLE), and biopsy-proven International Society of Nephrology/Renal Pathology Society Class III or IV lupus glomerulonephritis within approximately 14 months prior to randomization
* Persistently active nephritis defined as, proteinuria greater than 0.5g/day as determined by measurement of total urine protein less than 0.5 g/24- hours or a urine Protein/Creatinine (P/C) ratio greater than 0.5 (mg/mg) in a timed collection of 12 or more hours, for 2 months or more prior to the first administration of study medication and observed during at least 2 visits conducted 1 week apart during the screening period
* Active Class III or Class IV lupus nephritis determined by recent biopsy within approximately 6 months prior to screening or at least 1 of the following 3 criteria: hematuria (blood in urine), anti-DNA positivity, or low C3 or C4 complement levels
* Stable immunosuppression for at least 9 weeks prior to the first administration of study medication consisting of MMF 1-3 g/day (or equivalent dose of MPA) with/without corticosteroids up to prednisone equivalent of 20 mg/day, or azathioprine 1-3 mg/kg/day with/without corticosteroids up to prednisone equivalent of 20 mg/day
* Stable dose of angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blocker (ARB) for at least 9 weeks prior to the first administration of study medication
* If using oral corticosteroids, must be on a stable dose equivalent to 20 mg/day or less of prednisone for at least 9 weeks prior to the first administration of study medication

Exclusion Criteria:

* Cyclophosphamide use within 3 months of randomization
* B-cell depletion therapy within 6 months of screening, or evidence of persistent B-cell depletion at the time of screening
* Greater than 50 percent glomerular sclerosis on renal biopsy
* Serum creatinine \> 2.5 mg/dL (SI: \> 177 µmol/L)
* White blood cell count \< 3.5 x 10\^3 cells/µL (SI: \< 3.5 x 10\^9 cells/L) or neutrophils \< 1.96 x 10\^3 cells/µL (SI: \< 1.96 x 10\^9 cells/L)
* Platelets \< 140 x 103 cells/ µL (SI: \< 140 x 10\^9 cells/L)
D: 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 first randomization with a histologic diagnosis (ISN/RPS 2003 classification of LN) class III, IV, V;
4. Class IV LN: proteinuria \>1g/24hr or Scr\>115umol/L;
5. Class III or V LN: proteinuria \>2g/24hr or Scr\>115umol/L;
6. Provision of written informed consent by subject or guardian.

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 .

Answer: B