Mesenchymal Stem Cell Transplantation in the Treatment of Chronic Antibody Mediated Kidney Graft Rejection (ABMR)

Study Overview
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Brief Summary
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Transplant rejection is one of the biggest limitations in renal transplant procedures, where the kidney can undergo an acute, late acute, or chronic transplant rejection. With the advancement in transplantation protocols, acute survival of renal transplants has improved, but long-term survival is still unsatisfactory, as most of the renal transplants develop chronic graft rejection. Unfortunately, there is little the investigators know when it comes to improving long-term survival of renal transplants. Mesenchymal stem cells (MSC) have been shown to have immunosuppressive and repairing properties. The purpose of this study is to find out whether MSC in combination with standard therapy of antibody mediated rejection (ABMR) are more effective in preventing organ deterioration and maintaining kidney function.

Detailed Description
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Participants will be assigned to receive the full immunosuppressive therapy indicated to treat chronic ABMR (including plasmapheresis (PF) 7x, intravenous immune globulins 100 mg/kg 7x, corticosteroid) and MSC infusions (2x106cells/kg bw after PF) (Group 1) and be compared to historic controls according to propensity score matching (treated with immunosuppressive therapy alone (Group 2)). Patients will undergo MSC infusions at the start of the study after each PF. One year post- infusions, patients will be evaluated and undergo kidney biopsies. Blood collection will occur at regular intervals, serum creatinine and the estimated creatinine clearance will be monthly recorded. The transplanted kidney function and morphology (US Doppler) will be evaluated.

Official Title
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Autologous Mesenchymal Stem Cell Transplantation in the Treatment of Chronic Antibody Mediated Kidney Graft Rejection (ABMR)

Conditions
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Interventional

Intervention / Treatment
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* Other: MSC transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipients of a renal allograft, male and female patients age >18 The eGF>20 ml/min/1.73 m2, Renal biopsy Criteria: chronic active ABMR. Written informed consent, compliant with local regulations. Exclusion Criteria: Recipients of multiple organs. Pregnant women. Malignant disease in last 5 years Active autoimmune disease Active infection including hepatitis B, hepatitis C, HIV, or tuberculosis Evidence of congestive cardiac failure and/or acute coronary syndrome in past 6 months. Evidence of liver disease Inadequate compliance to treatment.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: comparison with historic control
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Historic control<br>historic cohort of patients with ABMR treated with standard of care therapy | |
| Experimental: MSC transplantation<br>patients with ABMR treated with MSC transplantation | Other: MSC transplantation<br>* MSC transplantation: patients with ABMR treated with MSC transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of MSC transplantation as assessed by adverse events according to CTCAE Version 5Estimated glomerular filtration rate (eGFR) | Adverse events according to CTCAE Version 5 | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated glomerular filtration rate (eGFR) | eGFR at up to 12 months post MSC transplantation | 12 months | 
| Graft survival rate | Graft survival rate at 12 months post MSC transplantation | 12 months |