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Pediatric Nephrology
Published in: Pediatric Nephrology 12/2016

01-12-2016 | Original Article

Sirolimus and tacrolimus coefficient of variation is associated with rejection, donor-specific antibodies, and nonadherence

Authors: Helen P. Pizzo, Robert B. Ettenger, David W. Gjertson, Elaine F. Reed, Jennifer Zhang, H. Albin Gritsch, Eileen W. Tsai

Published in: Pediatric Nephrology | Issue 12/2016

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Abstract

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.
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Metadata
Title
Sirolimus and tacrolimus coefficient of variation is associated with rejection, donor-specific antibodies, and nonadherence
Authors
Helen P. Pizzo
Robert B. Ettenger
David W. Gjertson
Elaine F. Reed
Jennifer Zhang
H. Albin Gritsch
Eileen W. Tsai
Publication date
01-12-2016
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 12/2016
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-016-3422-5

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