Inclusion Criteria:

• Age 1-65 years at the time of kidney transplant.
• Biopsy proven diagnosis of primary FSGS or minimal change disease.
• History of nephrotic syndrome (proteinuria, edema, hypoalbuminemia).
• First kidney transplant OR second or third kidney transplant with a history of recurrent FSGS in the first or second transplant
• The patient (if  ≥ 18 years old) or the child's parent or guardian must be able and willing to give written informed consent and comply with the requirements of the study protocol. Patient assent if < 18 years old will be required per local IRB requirements. 
• Negative urine pregnancy test prior to randomization (for females who are post-menarche). 
• Males and females of reproductive potential (sexually active in boys or post-menarche in girls) must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment with rituximab. An individual who meets any of the following criteria will be excluded from participation in this study: 
  • Known genetic cause of FSGS;
  • Patients with FSGS secondary to another condition (obesity, viral infection, medications, etc.);
  • Received rituximab within 1 year prior to transplant;
  • Known hypersensitivity to rituximab, to any of its excipients, or to murine proteins;
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies;
  • Known active bacterial, viral (e.g., HIV, hepatitis B, hepatitis C), fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with iv antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening visit;
  • Participation in another therapeutic trial within 30 days of enrollment or 5 half-lives of the investigational drug (whichever is longer);
  • ANC < 1.5 x 10^3;
  • Hemoglobin: < 8.0 gm/dL;
  • Platelets: < 100,000/mm;
  • AST or ALT > 2.5 x Upper Limit of Normal at the local institution's laboratory;
  • History of drug, alcohol, or chemical abuse within 6 months prior to screening visit;
  • Pregnant, lactating, or refusal of birth control in an adolescent of child-bearing potential;
  • Concomitant malignancies or previous malignancies; 
  • History of psychiatric disorder that would interfere with normal participation in this protocol;
  • History of significant cardiac (including arrhythmias) or pulmonary disease (including obstructive pulmonary disease);
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving 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;
  • Inability to comply with study and follow-up procedures.

Exclusion Criteria:

• Known genetic cause of FSGS.
• Patients with FSGS secondary to another condition (obesity, viral infection, medications, etc.).
• Received rituximab within 1 year prior to transplant.
• Known hypersensitivity to rituximab, to any of its excipients, or to murine proteins.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
• Known active bacterial, viral (e.g. HIV, hepatitis B, hepatitis C), fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with iv antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening visit.
• Participation in another therapeutic trial within 30 days of enrollment or 5 half-lives of the investigational drug (whichever is longer)
  • ANC < 1.5 x 10^3;
  • Hemoglobin:  < 8.0 gm/dL;
  • Platelets:  < 100,000/mm;
  • AST or ALT  > 2.5 x Upper Limit of Normal at the local institution’s laboratory.
• History of drug, alcohol, or chemical abuse within 6 months prior to screening visit.
• Pregnant, lactating, or refusal of birth control in an adolescent of child-bearing potential.
• Concomitant malignancies or previous malignancies.
• History of psychiatric disorder that would interfere with normal participation in this protocol.
• History of significant cardiac (including arrhythmias) or pulmonary disease (including obstructive pulmonary disease).
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving 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.
• Inability to comply with study and follow-up procedures.