Pilot Studies of Novel Therapies to Treat Resistant Focal Segmental Glomerulosclerosis (FSGS)

Inclusion Criteria:

1. Aged 2-42 years at onset of proteinuria
2. Aged ≤ 42 years at time of randomization (randomization date before 43rd birthday)

3. Estimated glomerular filtration rate (GFR) ≥ 40 ml/min/1.73 m2 at most recent measurement prior to randomization

   1. For patients < age 18 years: Schwartz formula
   2. For patients ≥ age 18 years: Cockroft-Gault formula
4. Up/c > 1.0 g/g creatinine on first morning void at time of randomization
5. Biopsy confirmed as primary FSGS (including all subtypes) by study pathologist.
6. Steroid resistance: During the last treatment course with high dose steroids prior to randomization, the patient must have demonstrated steroid resistance defined below and not have had a complete remission of proteinuria (Up/c < 0.2 or dipstick urine protein negative/trace) subsequently. The course of steroid treatment that defines resistance must be the same or equivalent to at least 4 weeks of every day dosing with a minimum cumulative dose of 56 mg/kg or 1680 mg of prednisone or its equivalent.
7. May be taking angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocking agent (ARB), vitamin E, or lipid lowering therapy
8. Willingness to comply with clinical trial protocol, medications, and follow-up visits, etc.
9. Screen failure in FSGS-CT based on prior treatment with excluded medication
10. Treatment failure in FSGS-CT based on failure to achieve remission after 26 weeks or 52 weeks of test therapy, i.e., cyclosporine or mycophenolate mofetil (MMF) + oral dexamethasone pulses

Exclusion Criteria

1. Secondary FSGS
2. Treated with cyclophosphamide, chlorambucil, levamisole, methotrexate, nitrogen mustard, or other immunosuppressive medications in the 30 days prior to randomization
3. Lactation, pregnancy, or refusal of birth control in women of child bearing potential
4. Participation in another therapeutic trial concurrently or for 30 days prior to randomization
5. Active/serious infection (including, but not limited to hepatitis B or C, HIV)
6. Malignancy
7. Systemic lupus erythematosus (SLE) or multiple sclerosis
8. Hepatic disease defined as serum AST/ALT > 2.5X the upper limit of normal
9. Patients with blood pressure > 140/95 or > 95th percentile for age/height while receiving maximal doses of 3 or more antihypertensive agents.
10. Diabetes mellitus (DM) type I or II.
11. Hematocrit < 30%
12. Organ transplantation

13. Obesity (based on estimated dry weight at disease onset prior to steroid therapy) defined as:

    1. Body mass index (BMI) > 97th percentile for age if aged 2-20 years
    2. BMI > 40 kg/m2 if aged ≥ 21 years
14. Allergy to study medications
15. Inability to consent/assent