Abrogation of antibodies improves outcome of renal transplantation.
BACKGROUND
Antibodies are known to cause rejection and therefore are detrimental to graft survival. We describe two protocols of clonal stimulation deletion (CSD) pretransplant followed by grafting with no conventional immunosuppression (IS).


METHODS
CSD was employed in 54 patients of mean age, 28.7 years and mean human leukocyte antigen A/B/DR match, 3.25. The two protocols both employed stimulation with donor-specific transfusions and stem cells with deletion using total lymphoid irradiation in group 1 (n = 29) or bortezomib in group 2 (n = 25). Other adjuvants in both protocols were cyclophosphamide, rabbit antithymocyte globulin, and rituximab. Stimulation and deletion were monitored by lymphocyte crossmatches and detection of donor-specific antibodies (DSA). Posttransplant monitoring included serum creatinine (SCr) measurements and antibody detection at regular intervals. Graft biopsy performed in the event of dysfunction was managed by standard guidelines. Rescue IS was initiated upon a rise in SCr or DSA.


RESULTS
Mean follow-up in group 1 is 3.28 years and 2.11 years in group 2. There was 100% graft and patient survivals in both cohorts with 23 patients without IS and stable graft function with an SCr of 1.3 mg/dL. All acute rejection episodes, which occurred among 24.1% of group 1 and 20% of group 2, were rescued with therapy evolving as a SCr of 1.6 to 1.9. The majority of rejections were antibody-combined with T-cell-mediated responses. We did not observe untoward effects of the protocol.


CONCLUSIONS
Abrogation of antibodies improved renal transplant outcomes.
Departments of Nephrology and Transplantation Medicine, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases and Research Centre, Dr H.L. Trivedi Institute of Transplantation Sciences, Gujarat, India. ikdrcad1@sancharnet.in
H L
HL
Trivedi
A V
AV
Vanikar
M R
MR
Gumber
H V
HV
Patel
P R
PR
Shah
V B
VB
Kute
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001803:Blood Transfusion; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D017637:Clonal Deletion; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007114:Immunization / Q000379:methods; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007194:India; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D015182:Lymphatic Irradiation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D011719:Pyrazines / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D001897:Boronic Acids; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D011719:Pyrazines; D000069286:Bortezomib; D003404:Creatinine