Abstract: SA-PO005
Trough Tacrolimus Levels in Kidney Transplant Recipients and Non-Melanoma Skin Cancer Risk over Follow Up
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
- Sexton, Donal J., Beaumont Hospital and The Royal College of Surgeons in Ireland, Dublin, Ireland
- Murray, Susan Louise, Beaumont Hospital and The Royal College of Surgeons in Ireland, Dublin, Ireland
- Conlon, Peter J., Beaumont Hospital, Dublin 9, Co Dublin, Ireland
Background
Whether Tacrolimus exposure is independently associated with non melanoma skin cancer (NMSC) incidence has not been fully characterised.
Methods
Retrospective analysis of the Irish National Kidney Transplant database linked with laboratory data from clinical practice. Generalised estimating equations with random effects were used to investigate repeated measures of trough Tacrolimus levels tested in clinical practice in recipients (as a time-varying covariate) and NMSC development. Exposure to Tacrolimus was also calcuated using the trapezoid rule to calcuate area under the curve (AUC), and time-averaged trough values. SAS v9.4 was used for data analysis.
Results
N=1540 kidney transplant recpieints were included, 95% of whom were deceased donor transplants and 41% female. 38% of donors were female. NMSC development (N=188), was independently associated with serum trough Tacrolimus levels over follow up (see table 1). However this association was not significant after adjusting for era of transplantation. This was true both of serum tacrolimus as a time-varying parameter and AUC Tacrolimus. Factors such as mean, median, min, max, and variability in Tacrolimus were not associated with NMSC overall. Limiations include possible confounding by overall imunnosupressive burden, survivor bias as well as the fact that follow up length and frequency of testing varied for each participant.
Conclusion
From repeated measures analysis of clinical practice laboratory data, while Tacrolimus exposure as measured by trough values and AUC associate with NMSC development over follow up, this association is attenuated after accounting for transplant vintage.
Results of generalized estimating equation analysis with trough Tacrolimus levels as a time-varying covariate
| Parameter | Estimate | Standard error | P value |
| Intercept | 4.05 | 0.58 | <0.001 |
| Tacrolimus trough | 0.006 | 0.003 | 0.003 |
| Recipient age | 0.06 | 0.008 | <0.001 |
| Recipient sex (female) | 0.69 | 0.24 | 0.004 |
| Number of kidney transplants | 0.73 | 0.2 | 0.0003 |
| Biopsy proven rejection within year 1 (clinical need) | 0.06 | 0.27 | 0.83 |
| PRA | 0.007 | 0.004 | 0.09 |
| Updated estimates after adjusting for era of transplantation and an interaction between era and Tacrolimus trough levels | |||
| Tacrolimus trough | 0.007 | 0.004 | 0.08 |
| Era (for Era 1) | 2.19 | 0.49 | <0.001 |
| Era by Tacrolimus trough interaction | 0.009 | 0.005 | 0.08 |