Long-term outcomes of kidney transplantation across a positive complement-dependent cytotoxicity crossmatch.
BACKGROUND
More than 30% of potential kidney transplant recipients have pre-existing anti-human leukocyte antigen antibodies. This subgroup has significantly lower transplant rates and increased mortality. Desensitization has become an important tool to overcome this immunological barrier. However, limited data is available regarding long-term outcomes, in particular for the highest risk group with a positive complement-dependent cytotoxicity crossmatch (CDC XM) before desensitization.


METHODS
Between 2002 and 2010, 39 patients underwent living-kidney transplantation across a positive CDC XM against their donors at our center. The desensitization protocol involved pretransplant immunosuppression, plasmapheresis, and low-dose intravenous immunoglobulin±rituximab. Measured outcomes included patient survival, graft survival, renal function, rates of rejection, infection, and malignancy.


RESULTS
The mean and median follow-up was 5.2 years. Patient survival was 95% at 1 year, 95% at 3 years, and 86% at 5 years. Death-censored graft survival was 94% at 1 year, 88% at 3 years, and 84% at 5 years. Uncensored graft survival was 87% at 1 year, 79% at 3 years, and 72% at 5 years. Twenty-four subjects (61%) developed acute antibody-mediated rejection of the allograft and one patient lost her graft because of hyperacute rejection. Infectious complications included pneumonia (17%), BK nephropathy (10%), and CMV disease (5%). Skin cancer was the most prevalent malignancy in 10% of patients. There were no cases of lymphoproliferative disorder. Mean serum creatinine was 1.7±1 mg/dL in functioning grafts at 5 years after transplantation.


CONCLUSIONS
Despite high rates of early rejection, desensitization in living-kidney transplantation results in acceptable 5-year patient and graft survival rates.
1 Schuster Family Transplantation Research Center, Renal Division, Brigham and Women's Hospital and Children's Hospital Boston, Harvard Medical School, Boston, MA. 2 Division of Transplant Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA. 3 Department of Nephrology, Beaumont Hospital, Dublin, Ireland. 4 Address correspondence to: Anil Chandraker, MD, Transplantation Research Center, Brigham and Women's Hospital and Children's Hospital Boston, 221 Longwood Ave, Boston MA 02115.
Leonardo V
LV
Riella
Kassem
K
Safa
Jude
J
Yagan
Belinda
B
Lee
Jamil
J
Azzi
Nader
N
Najafian
Reza
R
Abdi
Edgar
E
Milford
Helen
H
Mah
Steven
S
Gabardi
Sayeed
S
Malek
Stefan G
SG
Tullius
Colm
C
Magee
Anil
A
Chandraker
D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001900:Boston; D003131:Combined Modality Therapy; D003141:Communicable Diseases / Q000209:etiology; D003165:Complement System Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003888:Desensitization, Immunologic / Q000379:methods; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology; D010956:Plasmapheresis; D012307:Risk Factors; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
D058846:Antibodies, Monoclonal, Murine-Derived; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D000069283:Rituximab; D003165:Complement System Proteins