De Novo Donor-Specific Antibody Formation in Tacrolimus-Based, Mycophenolate Versus Mammalian Target of Rapamycin Immunosuppressive Regimens

Exp Clin Transplant. 2018 Feb;16(1):23-30. doi: 10.6002/ect.2016.0234. Epub 2017 Mar 22.

Abstract

Objectives: 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.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers / blood
  • Colorado
  • Drug Therapy, Combination
  • Female
  • Graft Rejection / blood
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • Histocompatibility
  • Hospitals, University
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Isoantibodies / blood*
  • Kidney Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / therapeutic use*
  • Pancreas Transplantation* / adverse effects
  • Prednisone / therapeutic use
  • Retrospective Studies
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Immunosuppressive Agents
  • Isoantibodies
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Mycophenolic Acid
  • Prednisone
  • Tacrolimus