Abstract: SA-PO003
The Epidemiologic Burden of Tacrolimus Variability Among US Kidney Transplant Recipients
Session Information
- Transplantation: Clinical Outcomes
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1802 Transplantation: Clinical
Authors
- Shah, Pratik B., University of Chicago, Chicago, Illinois, United States
- Ennis, Jennifer L., Litholink Corporation, Chicago, Illinois, United States
- Cunningham, Patrick, University of Chicago, Chicago, Illinois, United States
- Josephson, Michelle A., University of Chicago, Chicago, Illinois, United States
- McGill, Rita L., University of Chicago, Chicago, Illinois, United States
Background
Within-patient tacrolimus level variability has been shown to be a risk factor for de novo donor specific antibody (DSA) formation and increased death censored graft failure (DCGF) among kidney transplant recipients in single-center reports. We evaluated the correlation between subtherapeutic tacrolimus levels and tacrolimus variability in a large national data set.
Methods
We evaluated all tacrolimus levels drawn at any LabCorp® facility in the United States, between November 2011 and September 2017, with a diagnosis code for kidney transplant. Levels drawn within the six months after the earliest value were excluded, to exclude patients with new allografts. Patients were included if there were at least three tacrolimus levels thereafter. Tacrolimus variability was calculated as the coefficient of variability of the tacrolimus levels as: 100 x (standard deviation/mean) and compared to a risk threshold of 30% (Rodrigo et al., 2016). The percentage of subtherapeutic (< 4.0 ng/dL) tacrolimus levels (%subT) was calculated for each subject. The associations of tacrolimus variability with %subT were assessed with correlation analysis and linear regression.
Results
There were 410,257 tacrolimus levels among 27,375 patients, of whom 43.1% were women. Mean age was 52.5±14.4 years. Median follow-up was 26.5 (IQR=12.8-46.1) months. The median number of tacrolimus levels per patient was 11 (IQR=6-20). Median tacrolimus variability was 30.6%, with 51.6% of patients exceeding 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 a level of tacrolimus variability that has been previously associated with 2 to 3- fold increased hazards of DSA and DCGF. Tacrolimus variability has an association with subtherapeutic levels, but likely reflects a complicated constellation of clinical factors and scenarios that merit further study.