scholarly journals CYP3A5 genotype affects time to therapeutic tacrolimus level in pediatric kidney transplant recipients

2019 ◽  
Vol 23 (5) ◽  
Author(s):  
Megan V. Yanik ◽  
Michael E. Seifert ◽  
Jayme E. Locke ◽  
Vera Hauptfeld‐Dolejsek ◽  
Michael R. Crowley ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cyp3a5 Genotype ◽  
Tacrolimus Level

The Epidemiologic Burden of Tacrolimus Variability among Kidney Transplant Recipients in the United States

2019 ◽  
Vol 50 (5) ◽  
pp. 370-374 ◽  
Author(s):  
Pratik B. Shah ◽  
Jennifer L. Ennis ◽  
Patrick N. Cunningham ◽  
Michelle A. Josephson ◽  
Rita L. McGill
Keyword(s):  
United States ◽  
Linear Regression ◽  
Kidney Transplant ◽  
De Novo ◽  
The United States ◽  
National Sample ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Data Set ◽  
Tacrolimus Level

Background: Within-patient tacrolimus level variability >30% has been shown to be a risk factor for de novo donor-specific antibody formation and death-censored graft failure among kidney transplant recipients. The burden of tacrolimus variability and the correlation between variability and subtherapeutic tacrolimus levels were examined in a large national data set. Methods: All tacrolimus levels drawn at LabCorp® facilities in the United States with a diagnosis code for kidney transplant between November 2011 and September 2017 were examined, excluding values that could represent new allografts. Tacrolimus variability was calculated if at least 3 levels were available. The percentage of subtherapeutic (<4.0 ng/dL) tacrolimus levels (%subT) was also calculated. Interdependence between %subT and tacrolimus variability was assessed with correlation analysis and linear regression. Results: There were 410,257 tacrolimus levels among 27,375 patients, who had 11 (interquartile range [IQR] 6–20) tacrolimus levels over a median follow-up of 26.5 (IQR 12.8–46.1) months. Median tacrolimus variability was 30.6%, and 51.6% of patients exceeded 30% variability. Median %subT was 11.1% (IQR 0–30.8%), and 34.3% of patients had no subtherapeutic levels. The correlation coefficient between tacrolimus variability and %subT was 0.253 (p< 0.001). In linear regression, tacrolimus variability increased 1.86% for each 10% increase in %subT (p < 0.001), but R-squared for this model was only 0.06. Conclusion: More than half of established kidney transplant patients from a large national sample exhibited levels of tacrolimus variability that have been associated with inferior transplant outcomes. Tacrolimus variability has a weak association with subtherapeutic levels, but represents a more complicated constellation of clinical factors.

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