allograft fibrosis
Conditions
Interventions
Patients of the MSC treated groups will receive two doses of autologous bone
marrow (BM) derived MSCs IV, 7 days apart, 6 and 7 weeks after transplantation
in combination with Certican® (1.5 mg/b.i.
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Female or male, aged between 18 and 75 years. 2. Subject is willing to participate in the study, must be able to give informed consent and the consent must be obtained prior to any study procedure. 3. Recipients of a first kidney graft from a deceased, living-unrelated or non-HLA identical living related donor > 50 years of age. 4. Panel Reactive Antibodies (PRA)
Exclusion criteria
Exclusion criteria: 1. Double organ transplant recipient. 2. Biopsy proven acute rejection (according to the Banff criteria) in the first 6 weeks after transplantation (before MSC infusion). 3. Patients with evidence of active infection or abscesses (with the exception of an uncomplicated urinary tract infection) before MSC infusion. 4. Patients suffering from hepatic failure. 5. Patients suffering from an active autoimmune disease. 6. Patients who have had a previous BM transplant. 7. A psychiatric, addictive or any disorder that compromises ability to give truly informed consent for participation in this study. 8. Use of any investigational drug after transplantation. 9. Documented HIV infection, active hepatitis B, hepatitis C or TB according to current transplantation inclusion criteria. 10. Subjects who currently an active opportunistic infection at the time of MSC infusion (e.g., herpes zoster [shingles], cytomegalovirus (CMV), Pneumocystis carinii (PCP), aspergillosis, histoplasmosis, or mycobacteria other than TB, BK) after transplantation. 11. Malignancy (including lymphoproliferative disease) within the past 2-5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence) according to current transplantation inclusion criteria. 12. Known recent substance abuse (drug or alcohol). 13. Contraindications to undergo a BM biopsy. 14. Patients who are recipients of ABO incompatible transplants. 15. Cold ischemia time >30 hrs. 16. Patients with severe total hypercholesterolemia (>7.5 mmol/L) or total hypertriglyceridemia (>5.6 mmol/L) (patients on lipid lowering treatment with controlled hyperlipidemia are acceptable).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary end point is to compare fibrosis by quantitative Sirius Red scoring of MSC treated and untreated groups at 6 months compared to 4 weeks post transplant. | — |
Secondary
| Measure | Time frame |
|---|---|
| Composite end point efficacy failure (Biopsy Proven Acute Rejection (BPAR), graft loss, death or loss to follow-up) at 6 months; renal function measured by cGFR (MDRD formula and iohexol clearance) and proteinuria at 6 months; CMV and BK infection (viremia, disease and syndrome); adverse events; the presence of donor specific antibodies (DSA) and immune monitoring in the different treatment groups; to compare the progression of "subclinical" cardiovascular disease in the different treatment groups by assessing echocardiography and pulse wave velocity. | — |
Countries
Netherlands
Outcome results
None listed