A Pilot Study to Assess the Efficacy of Rituximab Therapy in Treatment Resistant FSGS

Inclusion Criteria: * FSGS involving native kidneys with a diagnostic biopsy performed within the last 3 years * Patients \>6 years of age and \< 80 years of age * suPAR \> 3500 pg ml-1 * Treatment with an ACEI and/or ARB as tolerated for at least 3 months prior to enrollment to with a target a systolic blood pressure ≤ 140 mmHg and a diastolic pressure ≤ 90 mmHg in adults and blood pressure readings less than the 95th percentile for age, gender and height in children in at least 75% of readings * Proteinuria ≥ 3.0 grams as measured by 24-hour urine collection in adults and urine protein:creatinine ratio ≥ 1.0 in the first morning urine in children, despite ACE inhibitor / ARB treatment as tolerated and a minimum of 8 weeks of prednisone therapy at ≥ 1 mg/kg/day, a trial of calcineurin inhibitor for=\> 3 months or a contraindication/intolerance to such therapy (diabetes, osteoporosis/osteonecrosis, age \>60, BMI ≥35) * Negative serum pregnancy test (for women of child bearing age) * Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of the trial * Able and willing to give written informed consent and comply with study requirements Exclusion Criteria: * Estimated GFR \< 40 ml/min per1.73m2. The rationale is that patients with advanced renal failure may progress rapidly towards ESRD. * Collapsing variant of FSGS, as it is rare and has been associated with an aggressive course * Concurrent use of immunosuppressive therapy with the exceptions of prednisone 10 mg/day. Patients who are taking other immunosuppressive therapy, must be off immunosuppressive medications for equal to or \> 3 months prior to enrollment into the study with the exception of patients demonstrating significant worsening of proteinuria (of \>30% above baseline) during the washout period. These resistant patients can be treated after 1 month of washout due to the high likelihood of progression and/or lack of delayed (previous) immunosuppression effect. * Patients with medical conditions that may cause FSGS (e.g. HIV, lymphoma, heroin use) or have a secondary form of FSGS due to hyperfiltration injury (massive obesity, vesicoureteral reflux, or renal mass reduction) * Type 1 or type 2 diabetes mellitus as diabetic glomerulosclerosis may be contributing to proteinuria in these patients * History of serious recurrent or chronic infection * Presence or suspicion of active infection including TB, HIV, Hepatitis B and HCV with positive tests for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis B virus (HBV), Hepatitis C serology, HIV serology or a positive TB skin test, which require further investigation to rule out active disease (ie. chest x-ray) * Known active infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks or oral antibiotics within 2 weeks of the study initiation * Low immunoglobulins (level to be based on age) * Absolute neutrophil count \< 1.5 x103/mL * Patients in receipt of a live vaccine within 4 weeks of the study initiation * Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix * Previous Treatment with a B-cell depleting antibody * History of severe allergic reactions to humanized or murine monoclonal antibodies * Treatment with any investigational agent within 4 weeks of the study initiation * History of major psychiatric disorder, drug or alcohol abuse within the previous 6 months * Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory that provides a reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications