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Related Experiment Video

Updated: Feb 26, 2026

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
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Class II Eplet Mismatch Modulates Tacrolimus Trough Levels Required to Prevent Donor-Specific Antibody Development.

Chris Wiebe1,2, David N Rush3, Thomas E Nevins4

  • 1Departments of Medicine, cwiebe@hsc.mb.ca.

Journal of the American Society of Nephrology : JASN
|July 22, 2017
PubMed
Summary

Donor-specific antibody development after kidney transplant is linked to HLA-DR/DQ epitope mismatch and lower tacrolimus levels. High-risk patients should avoid low tacrolimus trough levels to prevent antibody formation.

Keywords:
Human leukocyte antigenacute allograft rejectionallograft survivaldonor specific antibodykidney transplantationtacrolimus

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Area of Science:

  • Nephrology
  • Immunology
  • Transplantation

Background:

  • Optimal maintenance dosing of tacrolimus in kidney transplant recipients remains unclear.
  • Donor-specific antibody development is a major concern in kidney transplantation.

Purpose of the Study:

  • To investigate the correlation between tacrolimus trough levels, HLA-DR/DQ epitope mismatch, and de novo donor-specific antibody (dnDSA) development.
  • To identify risk factors for dnDSA development in kidney transplant recipients.

Main Methods:

  • Analysis of 50,011 serial tacrolimus trough levels from 596 renal transplant recipients.
  • HLA-DR/DQ epitope mismatch assessment using HLAMatchmaker software.
  • Statistical analysis of tacrolimus levels and dnDSA development in relation to HLA-DR/DQ epitope mismatch.

Main Results:

  • HLA-DR/DQ epitope mismatch independently predicted dnDSA development.
  • Recipients on tacrolimus had lower dnDSA incidence than those on cyclosporine.
  • Lower tacrolimus trough levels (<5 ng/ml) were associated with dnDSA development, particularly in high-risk patients.

Conclusions:

  • HLA-DR/DQ epitope mismatch and tacrolimus trough levels are independent predictors of dnDSA development.
  • Kidney transplant recipients with high HLA alloimmune risk should maintain tacrolimus levels above 5 ng/ml.
  • Monitoring for dnDSA is recommended for high-risk patients on tacrolimus therapy.