Pilot Study of Rituximab for Membranoproliferative Glomerulonephritis

Inclusion Criteria: MPGN either native/renal transplant kidneys with biopsy last 3 years Age > 18 years Urinary protein to creatinine ratio > 1.0 in a 24-hour urine collection, despite ACE inhibitor/ARB treatment Patients need to be treated with an ACEI and/or ARB, for at least 3 months prior to enrollment with the systolic blood pressure < 140 mm Hg for at least 75% of readings. Goal systolic blood pressure will be < 130 mm Hg.) Women must be post-menopausal, surgically sterile or practicing a medically approved method of contraception Patients intolerant of ACE inhibitors/ARBs may enter the study without being treated with these agents Able/willing to give written informed consent/comply with the requirements of study protocol Estimated GFR ≥ 25 ml/min per 1.73m^2 in the presence of ACE inhibitor/ARB therapy. The GFR will be estimated using the 4 variable Modification of Diet in Renal Disease (MDRD) equation/National Kidney Foundation - Chronic Kidney Disease (NKF-CKD) guidelines Adequate liver function, indicated by bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase levels not more than 2.5 times the upper normal limit 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 treatment Exclusion Criteria: Age <18 years. Estimated GFR < 25 ml/min per 1.73 m^2 Concurrent use of immunosuppressive therapy with the exceptions of prednisone 10 mg/day or less or an equivalent amount of another glucocorticoid or, among transplant patients, stable or decreasing transplant immunosuppression. Patient must be off immunosuppressive medications for > 3 months prior to enrollment into the study Medical conditions causing MPGN (e.g. HIV, hepatitis B, hepatitis C, systemic lupus erythematosus, monoclonal gammopathies). Patients with idiopathic cryoglobulinemia will not be excluded Presence or suspicion of active infection Type 1 or type 2 diabetes mellitus Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer) Receipt of a live vaccine within 4 weeks prior to randomization Previous Treatment with Rituximab (MabThera®/Rituxan®) or another B-cell depleting antibody History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies Human immunodeficiency virus (HIV) Hepatitis B or C History of recurrent significant or recurrent bacterial infections Known active bacterial, viral 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 i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening Ongoing use of high dose steroids(> 10 mg/day)or unstable steroid dose past 4 weeks Lack of peripheral venous access Drug,alcohol or chemical abuse within 6 months prior to screening Pregnancy(negative serum pregnancy test performed all women of childbearing potential within 7 days of treatment) Lactation Concomitant malignancies/previous malignancies within last 5 years, with the exception of adequately treated basal/squamous cell carcinoma of skin or carcinoma of cervix Major psychiatric disorder Significant cardiac or pulmonary disease Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory suspicion of a disease/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 Laboratory Exclusion Criteria (Screening): Hemoglobin:< 8.5 gm/dL Platelets:< 100,000/mm Total bilirubin,AST/alkaline phosphatase > 2.5 x Upper Limit of Normal unless related to primary disease Positive Hepatitis B or C serology Positive HIV