Rituximab to Prevent Recurrence of Proteinuria

Study Overview
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Brief Summary
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The investigators propose to study novel targets of rituximab in podocytes, with a particular focus on recurrent focal segmental glomerulosclerosis (FSGS). The proposed study has strong clinical implications, since it may extend the approved indications for rituximab treatment to recurrent FSGS as well as to other proteinuric diseases. Furthermore, it will offer new insights into the role of sphyngomyelin related enzymes in podocyte function in health and disease, thus allowing the identification of novel targets for antiproteinuric drug development. Finally, the proposed study offers the opportunity to identify a correlation between the patient's specific clinical outcome and the experimental results obtained after exposing podocytes to patient sera in the presence or absence of rituximab. Therefore, it may lead to the development of an assay for the pre-transplant identification of patients at high-risk for recurrent disease and, among them, may allow the identification of those patients that will respond to rituximab.

Detailed Description
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A total of 60 patients will be enrolled in the study.

Official Title
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The Use of Rituximab to Prevent Recurrence of Proteinuria in Patients Receiving Kidney Transplant for FSGS

Conditions
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FSGS, Proteinuria

Intervention / Treatment
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* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion: Patient has been fully informed and has signed a dated IRB-approval informed consent form. Age 7-65 years. Male and Females diagnosed of FSGS by kidney biopsy. Kidney biopsy report is not required once the physician confirms the diagnosis. Transcribed reports from referring physicians are also valid. Exclusion: Recipient or donor is seropositive for human immunodeficiency virus (HIV), Hepatitis C viruses, or Hepatitis B virus antigenemia. Patient has a current malignancy or a history of malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully or carcinoma in situ of the cervix that has been treated successfully. Patient has uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or an active peptic ulcer or any other unstable medical condition that could interfere with study objectives. Patient is pregnant or lactating. Patient has any form of substance abuse, psychiatric disorder or a condition that, in opinion of the investigator, may invalidate communication with the investigator. Patients with a defined genetic cause of FSGS.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rituximab<br>Participants will receive Rituximab post within 24 of Kidney Transplant | Drug: Rituximab<br>* Induction therapy<br>* Other names: Rituxan;|
| No Intervention: No rituximab<br>Participants will not receive Rituximab within 24 hours of Kidney Transplant | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Days 3-30. | Primary Outcome - Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Days 3-30 will be compared between the two treatment arms using an intent-to-treat approach. | between post-transplant day 3 and day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Months 3-12 | Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Months 3-12 will be compared between the two treatment arms using an intent-to-treat approach. | Post-Transplant Months 3-12 | 
| Renal Function as Measured by eGFR (Estimated Glomerular Filtration Rate) | Renal function as measured by eGFR (estimated glomerular filtration rate) using the MDRD formula | 12 months post-transplant |