Effects of Two Preemptive Post-transplant Desensitization Regimens Upon Renal Allograft Survival and DSA Elaboration.
We used a simple point-based algorithm to identify patients who might benefit from desensitization because of their higher risk of antibody-mediated chronic rejection and graft failure. Points were assigned to known but easily determined risk factors (panel reactive antibody, flow crossmatch, delayed graft function) and calculated immediately after deceased donor kidney transplantation. Point totals were used to identify: 1) which patients would receive desensitization; and, 2) which regimen each patient would receive. This standardized approached resulted in improved overall graft survival in both modalities compared to historically untreated sensitized patients. While preemptive desensitization positively impacted clinical metrics, the improvements were unequal between regimens. PP/IVIG treatment clearly resulted in greater elimination of preexisting donor specific antibodies against HLA antigens (DSA), fewer late rejections, and superior 3-year graft survival among patients who resolved their DSA as well as those with persistent DSA. Since graft survival among PP/IVIG recipients was excellent even when preexisting DSA were still present one year post-transplant, it suggests that the benefit of this regimen is two-fold: first to increase DSA elimination among patients, and secondly, to minimize downstream immune activating events such as rejection. In contrast, IVIG patients with persistent DSA had more rejections and graft survival only slightly better than if they had no treatment at all. Since the IVIG group also had a preponderance of Class II directed DSA, we cannot discount the influence of that specificity upon graft outcomes. Additional studies are needed to confirm our findings and to allow more effective assessment of the impact of DSA specificity upon desensitization efficacy and graft success.
Pamela M
PM
Kimball
Felecia A
FA
McDougan
Anne
A
King
D000328:Adult; D015415:Biomarkers / Q000097:blood; D003888:Desensitization, Immunologic / Q000379:methods; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / 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*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010956:Plasmapheresis; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007518:Isoantibodies