Belatacept Conversion in Proteinuric Kidney Transplant Recipients
Condition: Proteinuria
MeSH terms: Proteinuria
Intervention: Belatacept
Intervention description: Conversion from calcineurin-inhibitor to Belatacept maintenance immunosuppression.
Intervention MeSH terms: Abatacept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Proteinuria; Kidney transplantation; Allograft dysfunction; B7-1; Belatacept

Summary:

      Background: Proteinuria develops in about 30% of kidney transplant recipients and is a strong
      predictor of graft loss. The amount of proteinuria has a direct correlation with the risk of
      graft failure. Novel therapies are urgently needed to reduce proteinuria and prevent graft
      loss in transplant recipients, since ACE inhibitors carry a number of limitations in the
      transplant setting, including significant reduction in renal function, anemia and
      hyperkalemia.

      Preliminary data: B7-1 is expressed at significant levels in about 10% of kidney allograft
      biopsies with predominance in patients with proteinuria.

      Hypothesis: We hypothesize that B7-1 targeting therapy may reduce proteinuria and improve
      graft survival in proteinuric transplant recipients that have B7-1 staining on allografts. In
      addition, the absence of CNI nephrotoxicity and the potential protective effect of Belatacept
      on DSA production may be of benefit in this subset of transplant patients.

      Objectives:

      Primary: Determine the effect of Belatacept conversion in reducing proteinuria by 25% at 12
      months in renal transplant recipients (≥1gram/d) that are either B7-1-positive or negative on
      kidney biopsy.

      Secondary: Assess the effect of Belatacept conversion in the percent change of renal function
      from baseline to 12 months; donor-specific anti-HLA antibodies presence and intensity (MFI);
      correlation of B7-1 positivity on immunofluorescence on biopsy with B7-1-expression in urine
      extracellular vesicles; adverse events; acute rejection episodes; blood pressure control; new
      onset diabetes; hyperlipidemia; graft survival; and patient survival.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female adult kidney transplant recipients older than 18 years old

          2. eGFR ≥30 ml/min

          3. ≥6 months after transplantation

          4. Proteinuria ≥1 gram/day in spot urine protein/creatinine ratio

          5. Ability to provide written informed consent for the study.

          6. Maintenance immunosuppression of CNI (cyclosporine or tacrolimus), antiproliferative
             agent (azathioprine, MMF or MPA) with either steroids or not.

        Exclusion Criteria:

          1. Age <18 years

          2. eGFR<30 ml/min

          3. active acute cellular rejection (ACR; higher than borderline) or ACR in the previous 6
             months; active acute antibody-mediated rejection

          4. recurrent FSGS

          5. EBV IgG negative

          6. patient on mTOR inhibitor (e.g. Everolimus, Sirolimus)

          7. patient only on CNI (cyclosporine or tacrolimus) and steroids