Kidney Transplantation
Conditions
Keywords
kidney transplantation, antibody-mediated rejection, mesenchymal stem cell therapy, donor specific antibody, acute rejection
Brief summary
This study is designed to investigate the efficacy and safety of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) on chronic antibody-mediated rejection (cAMR) after kidney transplantation. Chronic AMR is diagnosed according to Banff criteria 2013 based on renal graft biopsy and donor specific antibodies (DSA) examination. cAMR patients are assigned to MSCs group or control group. Patients in control group are prescribed to current desensitization therapy including at least one of the following treatments: plasmapheresis (PP), intravenous immunoglobulin (IVIG), rituximab or Bortezomib, depending on individual pathological and immunological features (eg. DSA type and titer) of each study subjects. Patients in MSCs group receive additional BM-MSCs therapy besides desensitization treatments as in control group. Allogeneic BM-MSCs (1\*10\^6/kg) are intravenously administered every two weeks for four consecutive doses. All cAMR patients are followed up for one year. Renal function, DSA level, pathological features, patient/graft survival, and severe adverse events are monitored during the follow-up period. Immunological features of patients in both groups are consecutively examined.
Interventions
OTHERBM-MSCs
BM-MSCs are from third-party healthy donors, and have no HLA alleles similar to renal allograft donors or reacting to positive anti-HLA antibodies in recipients.
OTHERDesensitization therapy (PP, IVIG, rituximab or Bortezomib)
At least one drug or treatment is applied as desensitization therapy to decrease DSA, reduce B cells or inhibit plasma cells, depending on individual condition.
Sponsors
Second Affiliated Hospital of Guangzhou Medical University
First Affiliated Hospital, Sun Yat-Sen University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* kidney transplantation * cAMR diagnosis is determined based on renal graft biopsy and DSA examination * Patient is willing and capable of giving written informed consent for study participation and able to participate in the study for 12 months
Exclusion criteria
* Combined or multi-organ transplantation * Women who are pregnant, intend to become pregnant in the next 1 years, breastfeeding, or have a positive pregnancy test on enrollment or prior to study medication administration * Donors or recipients are known hepatitis C antibody-positive or polymerase chain reaction (PCR) positive for hepatitis C * Donors or recipients are known hepatitis B surface antigen-positive or PCR positive for hepatitis B * Donors or recipients are known human immunodeficiency virus (HIV) infection * Patients with active infection * Recipients with a history of substance abuse (drugs or alcohol) within the past 6 months, or psychotic disorders that are not capable with adequate study follow- up * Patients with severe cardiovascular dysfunction * WBC\<3\*10\^9/L or RBC \<5g/dL * Highly allergic constitution or having severe history of allergies * Patients with active peptic ulcer disease, chronic diarrhea, or gastrointestinal problem affect absorption * Patients with a history of cancer within the last 5 years * Prisoner or patients compulsorily detained (involuntarily incarcerated) for treatment or either a psychiatric or physical (e.g. infectious disease) illness * Renal graft function deteriorates due to non-immunological complication, such as surgical issues or drug nephrotoxicity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimated glomerular filtration rate (eGFR) | 12 months | eGFR at month 12 after enrollment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient survival rate | 12 months | patient survival rate at month 12 after enrollment |
| Graft survival rate | 12 months | graft survival rate at month 12 after enrollment |
| Donor specific antibody (DSA) level | 12 months | Change of DSA level up to 12 months after enrollment |
| Pathological manifestation | 12 months | Change of pathological scores according to Banff 2013 criteria |
| Severe adverse events | 12 months | — |
Countries
China
Contacts
Primary ContactChangxi Wang, M.D., Ph.D
Backup ContactLongshan Liu, M.D., Ph.D
Outcome results
None listed