Risk of graft failure according to degree of proteinuria.

This research study will assess the benefit of a novel immunosuppressive medication (Belatacept) in kidney transplant patients with proteinuria. Leaking protein in the urine (proteinuria) is a major risk factor for loosing a transplanted kidney (see figure below) and there are no clear therapy that has shown to reduce proteinuria and improve kidney survival in transplantation. B7-1 is a molecule that is potentially responsible for proteinuria in some patients and can be target by a new class of drugs in the market, which include Abatacept and Belatacept. Preliminary data is our laboratory indicates that B7-1 is expressed at significant levels in about 10% of kidney allograft biopsies with predominance in patients with proteinuria.

Our plan is to convert patients from Tacrolimus to Belatacept for 12 months and measure the reduction of proteinuria at 12 months. We will also monitor the kidney function, the appearance of anti-HLA antibodies, B7-1 markers in the urine, acute rejection and infections episodes. We plan to enroll 2 groups of patients: those that are B7-1 positive on biopsy and those that are B7-1 negative, since it is not clear if positivity on biopsy correlates with response to treatment.

Study design without numbers

Study Design.

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. Available biopsy specimen for B7-1 staining at recruitment time.
  6. Ability to provide written informed consent for the study.
  7. 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

Update December 2014: This trial is not enrolling yet. Enrollment is planned to start on March 2015.

Belatacept in Proteinuric
Patients Study

Principal Investigator

Leonardo V. Riella, MD, PhD