Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival

Gallagher, Harry M., Sarwar, Ghulam, Tse, Tracy, Sladden, Timothy M., Hii, Esmond, Yerkovich, Stephanie T., Hopkins, Peter M. and Chambers, Daniel C. (2015) Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival. Journal of Heart and Lung Transplantation, 34 11: 1442-1448. doi:10.1016/j.healun.2015.05.028

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Author Gallagher, Harry M.
Sarwar, Ghulam
Tse, Tracy
Sladden, Timothy M.
Hii, Esmond
Yerkovich, Stephanie T.
Hopkins, Peter M.
Chambers, Daniel C.
Title Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival
Journal name Journal of Heart and Lung Transplantation   Check publisher's open access policy
ISSN 1557-3117
1053-2498
Publication date 2015-11-01
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.healun.2015.05.028
Open Access Status File (Author Post-print)
Volume 34
Issue 11
Start page 1442
End page 1448
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher Elsevier USA
Language eng
Formatted abstract
Background: Erratic tacrolimus blood levels are associated with liver and kidney graft failure. We hypothesized that erratic tacrolimus exposure would similarly compromise lung transplant outcomes. This study assessed the effect of tacrolimus mean and standard deviation (SD) levels on the risk of chronic lung allograft dysfunction (CLAD) and death after lung transplantation.

Methods: We retrospectively reviewed 110 lung transplant recipients who received tacrolimus-based immunosuppression. Cox proportional hazard modeling was used to investigate the effect of tacrolimus mean and SD levels on survival and CLAD. At census, 48 patients (44%) had developed CLAD and 37 (34%) had died.

Results: Tacrolimus SD was highest for the first 6 post-transplant months (median, 4.01; interquartile range [IQR], 3.04–4.98 months) before stabilizing at 2.84 μg/liter (IQR, 2.16–4.13 μg/liter) between 6 and 12 months. The SD then remained the same (median, 2.85; IQR, 2.00–3.77 μg/liter) between 12 and 24 months. A high mean tacrolimus level 6 to 12 months post-transplant independently reduced the risk of CLAD (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.63–0.86; p < 0.001) but not death (HR, 0.96; 95% CI, 0.83–1.12; p = 0.65). In contrast, a high tacrolimus SD between 6 and 12 months independently increased the risk of CLAD (HR, 1.46; 95% CI, 1.23–1.73; p < 0.001) and death (HR, 1.27; 95% CI, 1.08–1.51; p = 0.005).

Conclusions: Erratic tacrolimus levels are a risk factor for poor lung transplant outcomes. Identifying and modifying factors that contribute to this variability may significantly improve outcomes.
Keyword Erratic tacrolimus levels
Lung transplant
Chronic lung allograft dysfunction
CLAD
Death
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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