Excellent renal allograft survival in donor-specific antibody positive transplant patients-role of intravenous immunoglobulin and rabbit antithymocyte globulin.
BACKGROUND
Timely transplantation of sensitized kidney recipients remains a challenge. Patients with a complement-dependent cytotoxicity negative and flow cytometry (FC) positive crossmatch carry increased risk of antibody-mediated rejection and thus graft loss. Solid phase assays are available to confirm donor specificity for antibody identified by FC crossmatch. Treatment using induction therapy with rabbit antithymocyte globulin (RATG) and intravenous immunoglobulin (IVIG) may allow successful transplant of these high-risk patients.


METHODS
A retrospective study of 264 consecutive patients after exclusions yielded 94 complement-dependent cytotoxicity anti-human globulin crossmatch-negative patients, including group 1: 58 primary transplants with panel-reactive antibody (PRA) less than 20%, group 2: 16 retransplants and PRA more than 20% who were FC crossmatch-negative, and group 3: 20 retransplants and PRA more than 20% who were FC crossmatch-positive. All were treated with RATG induction and maintenance therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. Only group 3 received IVIG at 500 mg/kg daily in three doses.


RESULTS
Eighteen of 20 patients in group 3 had donor-specific antibody identified by solid phase assay. Cellular- and antibody-mediated rejections were statistically higher in group 3. Two-year serum creatinine and glomerular filtration rate along with 3-year patient and graft survival were comparable between the groups.


CONCLUSIONS
Sensitized patients with positive FC crossmatch and donor-specific antibody identified by solid phase assays can be successfully transplanted using standard RATG induction, IVIG, and maintenance immunosuppression with equal renal function and graft survival to immunologically lower risk recipients. Given these results, this patient group should not be excluded from transplantation based on antibody specificities determined by virtual crossmatch techniques.
Mai
Martin L
ML
Department of Transplantation, Mayo Clinic, Jacksonville, FL 32224, USA. mai.martin@mayo.edu
Ahsan
Nasimul
N
Wadei
Hani M
HM
Genco
Petrina V
PV
Geiger
Xochiquetzal J
XJ
Willingham
Darrin L
DL
Taner
C Burcin
CB
Hewitt
Winston R
WR
Grewal
Hani P
HP
Nguyen
Justin H H
JH
Hughes
Christopher B
CB
Gonwa
Thomas A
TA
D000328:Adult; D000368:Aged; D000818:Animals; D000906:Antibodies / Q000097:blood*; D000918:Antibody Specificity; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D003601:Cytotoxicity Tests, Immunologic; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D012189:Retrospective Studies; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
D000906:Antibodies; D000961:Antilymphocyte Serum; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents