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Updated: Oct 3, 2026
Trans-vivo Delayed Type Hypersensitivity Assay for Antigen Specific Regulation
Published on: May 2, 2013
Sirolimus and tacrolimus coefficient of variation is associated with rejection, donor-specific antibodies, and
Helen P Pizzo1, Robert B Ettenger2, David W Gjertson3
1Division of Pediatric Nephrology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. helen.pizzo@cshs.org.
Background:
Immunosuppression medication nonadherence has been associated with donor-specific antibodies and treatment-refractory rejection. Drug-level monitoring is a practical direct marker for nonadherence, as variations indicate erratic ingestion of medication. We previously reported that high variability in tacrolimus trough levels determined by the percent coefficient of variation (CV %) and standard deviation (SD) were associated with biopsy-proven rejection. We hypothesized that the CV % and SD in patients on a sirolimus/low-dose tacrolimus regimen may associate with self-reported medication nonadherence, rejection and donor-specific antibodies.
Methods:
In this pilot feasibility study, we studied 37 biopsies in 23 pediatric renal transplant patients on both sirolimus and tacrolimus immunosuppression; CV %, SD, de novo donor-specific antibodies, rejection, and self-reported adherence were examined.
Results:
A cut-off sirolimus CV % of 25 maximized the percentage of biopsies correctly classified as rejection (32 of 37, or 86 %, p = 0.001). A cut-off tacrolimus CV % of 31 maximized the percentage of correctly classified biopsies (25 of 37, or 68 %, p = 0.09). Among patients with both high sirolimus and tacrolimus CV %, 67 % developed de novo donor-specific antibodies (p = 0.002) with a DQ predominance and 71 % reported nonadherence (p = 0.05).
Conclusions:
In pediatric renal transplantation, sirolimus and tacrolimus CV % is a potential tool for monitoring patients at risk for allograft rejection and donor-specific antibodies secondary to medication nonadherence.
