Improved graft survival in highly sensitized patients undergoing renal transplantation after the introduction of a clinically validated flow cytometry crossmatch.
BACKGROUND
Flow cytometric techniques are increasingly used in pretransplant crossmatching, although there remains debate regarding the clinical significance and predictive value of donor-specific antibodies detected by flow cytometry. At least some of the discrepancies between published studies may arise from differences in cutoffs used and lack of standardization of the test.


METHODS
We selected cut-off values for pretransplant flow cytometric crossmatching (FCXM) based on the correlation of retrospective results with the occurrence of antibody-mediated rejection. The impact on long-term renal graft survival of prospective FCXM was determined by comparing graft survival between patients crossmatched with complement-dependent cytotoxicity (CDC) only with those prospectively crossmatched with both CDC and FCXM.


RESULTS
Chosen cut-off values gave a positive predictive value of FCXM for antibody-mediated rejection of 83%, and a negative predictive value of 90%. After the introduction of prospective B- and T-cell crossmatching by flow cytometry in addition to CDC in our center, there was a significant improvement in renal graft survival in highly sensitized patients (P=0.017). Four-year graft survival in highly sensitized patients after the introduction of FCXM was 89%, which did not differ significantly from that seen in nonsensitized patients (93%; P=0.638).


CONCLUSIONS
Our data demonstrate that prospective FCXM improves renal transplant outcome in highly sensitized patients, provided that cut-off values are carefully validated and results interpreted in the context of sensitization history and antibody screening results.
National Histocompatibility and Immunogenetics Service for Solid Organ Transplantation, Beaumont Hospital, Dublin, Ireland.
Sandhya
S
Limaye
Patrick
P
O'Kelly
Grainne
G
Harmon
Derek
D
O'Neill
Anthony M
AM
Dorman
Joseph
J
Walshe
John
J
Donohoe
Dilly
D
Little
Peter J
PJ
Conlon
Mary T
MT
Keogan
D001402:B-Lymphocytes / Q000276:immunology; D005434:Flow Cytometry / Q000379:methods; D006085:Graft Survival / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007114:Immunization; D007518:Isoantibodies / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D011237:Predictive Value of Tests; D016019:Survival Analysis; D017741:Survivors; D013601:T-Lymphocytes / Q000276:immunology
D007518:Isoantibodies