De Novo Donor-Specific Antibody Formation in Tacrolimus-Based, Mycophenolate Versus Mammalian Target of Rapamycin Immunosuppressive Regimens.
De novo donor-specific antibody formation posttransplant is associated with decreased graft survival. It is not known whether mammalian target of rapamycin inhibitors may be advantageous or detrimental compared with mycophenolate in the prevention of de novo donor-specific antibody formation.



We compared 66 kidney and kidney-pancreas transplant recipients who received tacrolimus, mammalian target of rapamycin inhibitor, and prednisone (group 1; 36 of whom received everolimus and 30 of whom received sirolimus) versus 132 patients who received tacrolimus, mycophenolate, and prednisone (group 2) matched for age, sex, race, and type/timing of transplant from 2007 to 2012.



Rates of de novo donor-specific antibody formation were comparable between groups at 1, 6, and 12 months (16.7%, 25.8%, and 28.8% for group 1 vs 9.8%, 15.2%, and 22.0% for group 2). There were no significant differences in class (I, II, or mixed), strength (mean fluorescence intensity) of de novo donor-specific antibody, glomerular filtration rate, proteinuria levels, or acute rejection between the groups. In those with de novo donor-specific antibody by 6 months, acute rejection was more common versus those without de novo donor-specific antibody formation (24.3% vs 5.6% at 6 mo; P = .002), with rates of 27.0% versus 6.8% at 1 year (P = .001) and 40.7% versus 11.3% at 2 years (P < .001). An associated reduction in glomerular filtration rate also occurred.



Mammalian target of rapamycin inhibitors were neither protective nor permissive for de novo donor-specific antibody formation versus mycophenolate when used with clinically relevant tacrolimus dosing regimens.
New York-Presbyterian/Weill Cornell Medical Center, New York, NY, USA.
Zain
Z
Mithani
Jane
J
Gralla
Oluwafisayo
O
Adebiyi
Patrick
P
Klem
James E
JE
Cooper
Alexander C
AC
Wiseman
D000328:Adult; D015415:Biomarkers / Q000097:blood; D003120:Colorado; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006648:Histocompatibility; D006785:Hospitals, University; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D016035:Pancreas Transplantation / Q000009:adverse effects; D011241:Prednisone / Q000627:therapeutic use; D012189:Retrospective Studies; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D007166:Immunosuppressive Agents; D007518:Isoantibodies; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus