Clinical Research Directory

Inclusion Criteria: * Age 2-40 years at onset of signs or symptoms of FSGS * Age ≤ 40 years at time of randomization (randomization date before 41st birthday) * Estimated GFR ≥ 40 ml/min/1.73 m2 at most recent measure prior to randomization * For participants \< age 18 years: Schwartz formula * For participants ≥ age 18 years: Cockroft-Gault formula * Up/c \> 1.0 g protein/g creatinine on first am void at time of randomization * Biopsy confirmed as primary FSGS (including all subtypes) by study pathologist. A minimum of 1 glomerulus demonstrating segmental sclerosis on light microscopy will be required to confirm the diagnosis. * Steroid resistance: The participant must have demonstrated steroid resistance (defined as a failure to achieve a sustained Up/c ≤ 1.0) based on at least one treatment course with high dose steroids prior to randomization which satisfies both of the following conditions: * minimal treatment duration of 4 weeks * minimum cumulative dose of 56 mg/kg or 1680 mg of prednisone or its equivalent. In addition, the participant must not have had a complete remission of proteinuria (Up/c \< 0.2 or dipstick urine protein 0/trace) subsequent to the latest qualifying 4-week course demonstrating steroid resistance. * Willingness to follow the clinical trial protocol, including medications, and baseline and follow-up visits and procedures. * Participants may be taking ACEI, ARB, Vitamin E, or lipid lowering therapy. Exclusion Criteria: * Secondary FSGS * Prior therapy with sirolimus, CSA, tacrolimus, MMF, or azathioprin (Imuran) * Treated with cytoxan, chlorambucil, levamisole, methotrexate, or nitrogen mustard in the last 30 days * Lactation, pregnancy, or refusal of birth control in women of child bearing potential * Participation in another therapeutic trial concurrently or 30 days prior to randomization * Active/serious infection (including, but not limited to Hepatitis B, C, or HIV) * Malignancy * Blood pressure \> 140/95 or \> 95th percentile for age/height. * Participant is receiving 4 or more antihypertensive agents for the primary purpose of controlling blood pressure. * Participants with previously diagnosed diabetes mellitus type I or II: the diagnosis of DM I or II will be based on local criteria for participants with an established diagnosis. If hyperglycemia is detected during the screening period, the WHO criteria for the diagnosis of DM I and II will be used. * Clinical evidence of cirrhosis or chronic active liver disease * Abnormal laboratory values at the time of study entry: * Absolute neutrophil count (ANC) \< 2000/mm3, or * Hematocrit (HCT) \< 28% * History of significant gastrointestinal disorder, e.g, severe chronic diarrhea (\> 5 watery stools per day) or active peptic ulcer disease. * Organ transplantation * Obesity (based on estimated dry weight at onset of disease prior to steroid therapy) defined as * BMI \> 97th percentile for age if aged 2-20 years * BMI \> 40 kg/m2 for age ≥21 years * Allergy to study medications * Inability to consent/assent Note: Participants with conditions meeting exclusion criteria at a particular evaluation for eligibility may be re-evaluated at a later time to determine if the conditions have changed so that all entry criteria are met. In particular, if blood pressure \> 140/95 or \> 95th percentile for age/height while the participant is on less than three antihypertensive agents, the participant may be re-evaluated for eligibility after adding other antihypertensive agents so long as the total number of agents does not exceed three.