title: The effect of stem cell transplantation on immunosuppression in living donor renal transplantation: a clinical trial.
abstract: OBJECTIVE
  We designed a clinical trial on a group of live-donor renal transplantation (LDRT) patients subjected to pre-transplant stem cell transplantation (SCT) to minimize immunosuppression to low-dose steroid monotherapy.
  
  
  METHODS
  LDRT patients subjected to pretransplant SCT who had stable graft function for ≥2 years and serum creatinine (SCr) <2 mg/dL were recruited. Patients with diabetes, hepatitis C/B, rejections, or unwilling to participate, were excluded. They had been subjected to non-myeloablative conditioning of total lymphoid irradiation (TLI)/bortezomib and cyclophosphamide, rabbit-antithymocyte globulin (r-ATG) and rituximab with SCT. The maintenance immunosuppression consisted of calcineurin inhibitors (CNI) and/or anti-proliferative agents and prednisone. Donor-specific antibodies (DSA) and peripheral T-regulatory cells (CD127(low/-)/4(+)/25(high)) (p-Tregs) were studied before and after withdrawal of major immunosuppressants; graft biopsy was taken after 100 days of withdrawal in willing patients. Rejections were planned to be treated by anti-rejection therapy followed by rescue immunosuppression.
  
  
  RESULTS
  All immunosuppression but prednisone, 5-10 mg/day has been successfully withdrawn for a mean of 2.2 years in 76 patients with a mean age of 31.4 years and a mean donor-recipient HLA match of 2.9. The mean SCr of 1.4 mg/dL and p-Tregs of 3.5% was remained stable after withdrawal; DSA status was negative in 35.5% and positive in 47.4% patients. Protocol biopsies in all 10 patients who gave the consent were unremarkable.
  
  
  CONCLUSIONS
  Stable graft function in LDRT on low-dose steroid monotherapy using pre-transplant SCT under non-myeloablative conditioning with generation of p-Tregs can be achieved successfully and safely.
authors.affiliation: Department of Nephrology and Transplantation Medicine.
authors.forename: H L
authors.initials: HL
authors.lastname: Trivedi
authors.affiliation: Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, G. R. Doshi and K. M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H. L. Trivedi Institute of Transplantation Sciences (ITS), Asarwa, Ahmedabad-380016, Gujarat, India.
authors.forename: A V
authors.initials: AV
authors.lastname: Vanikar
authors.affiliation: Department of Nephrology and Transplantation Medicine.
authors.forename: V B
authors.initials: VB
authors.lastname: Kute
authors.affiliation: Department of Nephrology and Transplantation Medicine.
authors.forename: H V
authors.initials: HV
authors.lastname: Patel
authors.affiliation: Department of Nephrology and Transplantation Medicine.
authors.forename: M R
authors.initials: MR
authors.lastname: Gumber
authors.affiliation: Department of Nephrology and Transplantation Medicine.
authors.forename: P R
authors.initials: PR
authors.lastname: Shah
authors.affiliation: Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, G. R. Doshi and K. M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H. L. Trivedi Institute of Transplantation Sciences (ITS), Asarwa, Ahmedabad-380016, Gujarat, India.
authors.forename: S D
authors.initials: SD
authors.lastname: Dave
authors.affiliation: Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, G. R. Doshi and K. M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H. L. Trivedi Institute of Transplantation Sciences (ITS), Asarwa, Ahmedabad-380016, Gujarat, India.
authors.forename: V B
authors.initials: VB
authors.lastname: Trivedi
keywords: Clonal deletion; Graft rejection; Hematopoietic stem cells; Immunosuppression; Mesenchymal stem cells; Renal transplantation; T-Lymphocytes; regulatory