HLA antibody-incompatible renal transplantation had a high success rate if the CDC XM was negative. Further work is required to predict which CDC+ve XM grafts will be successful and to treat slowly progressive graft damage because of DSA in the first few years after transplantation.
We conclude that ADPKD is a significant risk factor for the development of NODAT. This may influence the follow up and management choices of these patients in the future.
These data raise the possibility that, in high immunologic risk patients undergoing Ai transplantation, the presence of elevated pretransplantation serum BAFF might identify those at increased risk of AMR. BAFF neutralization may be an interesting therapeutic strategy to explore in these patients, particularly because such agents are available and have already been used in the treatment of autoimmunity.
These data suggest that the dominant method of successful transplantation was function of the transplant in the presence of circulating DSA, and they also define the period during which this occurred.
Double filtration plasmapheresis (DFPP) was used in preference to plasma exchange in our program of antibody-incompatible transplantation, to treat higher volumes of plasma. Forty-two patients had 259 sessions of DFPP, 201 pre-transplant and 58 post-transplant. At the first treatment session, the mean plasma volume treated was 3.81 L (range 3-6 L), 55.5 mL/kg (range 36.2-83.6 mL/kg). Serum IgG fell by mean 59.4% (SD 10.2%), and IgM by 69.3% (SD 16.1%). Nine patients did not require increases in plasma volumes treated, and six did not tolerate higher plasma volumes. In the remaining patients, the mean maximum plasma volume treated pre-transplant was 6.67 L (range 4-15 L), 96.1 mL/kg (range 60.2-208.9 mL/kg). The complement dependent cytotoxic crossmatch was positive in 14 cases pre-treatment, and remained positive in six (42.8%) cases. The flow cytometric crossmatch was positive in 29 cases pre-treatment, and in 21 (72.4%) after DFPP. Post-transplant, DFPP was ineffective at reducing donor specific antibody levels during periods of rapid donor specific antibody synthesis. Post-transplant, the one year graft survival rate was 94%, although there was a high rate of early rejection. In summary, DFPP enabled the treatment of plasma volumes that were almost double those that would have been feasible with plasma exchange. Despite this, most patients were transplanted with a positive crossmatch, and DFPP post-transplant was unable to control rising antibody levels.
DSA levels may change markedly in the first month after antibody incompatible transplantation, and the risk of rejection was associated with higher pretreatment and peak levels.
Current methods of measuring ABO antibody levels based on the hemagglutination (HA) titers have the disadvantages of relatively poor reproducibility and do not offer fine discrimination of antibody concentration. We therefore developed a simple and rapid method of measuring ABO antibody levels using flow cytometry (FC). For validation, we analyzed plasma samples from 79 blood donors. Both IgM and IgG were detected and measured with IgG essentially restricted blood group O donors. Forty-two successive samples were collected from a patient with blood group O undergoing antibody removal and subsequent transplantation from a group A2 donor and tested by both HA and FC. Changes in IgG measured by FC (relative median fluorescence) correlated well with HA titers and importantly rejection episodes were preempted by a rising relative median fluorescence. The method allowed quantitative discrimination in the range of antibody levels relevant to ABO incompatible transplantation and has the advantages over HA of objective measurement and reproducibility.
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