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Abstract: PO2581

Assessing Cumulative Immunosuppressive Drug Exposure: Metrics, Outcomes, and Implications for Kidney and Non-Kidney Transplant Patients

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Skanthan, Cavizshajan, University Health Network, Toronto, Ontario, Canada
  • Nguyen, Emily, University Health Network, Toronto, Ontario, Canada
  • Somaweera, Lakindu, University Health Network, Toronto, Ontario, Canada
  • Rabindranath, Madhumitha, University Health Network, Toronto, Ontario, Canada
  • Famure, Olusegun, University Health Network, Toronto, Ontario, Canada
  • Kim, Joseph, University Health Network, Toronto, Ontario, Canada
Background

Immunosuppressive drugs are used in the long-term management of post-transplant patients to prevent rejection of transplanted organs. Lacking a prior qualitative systematic review on this topic, we aimed to characterize the metrics used to measure cumulative immunosuppressant exposure and their associated outcomes in kidney and non-kidney transplant patients.

Methods

We conducted a literature search using search terms related to immunosuppressants and cumulative exposure in Ovid MEDLINE, Ovid EMBASE, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews. No date restrictions were applied. An additional search was performed on Google Scholar and references of studies included in the primary search were screened. Studies were limited to the English language with adult human transplant patient populations. Study risk of bias was assessed using the Quality in Prognostic Studies Tool where each domain was rated as low, medium, or high risk of bias.

Results

A total of 29 articles were included in our qualitative synthesis. Kidney transplant populations account for 12 (41%) of the studies in our analyses. Fifteen of the articles (51%) calculated the total dose of immunosuppression over the treatment period while 9 (31%) used long term area-under-the-curve (LT-AUC) of trough level concentrations to quantify cumulative immunosuppression exposure. Nine articles found certain cumulative exposure metrics to be predictive of adverse outcomes such as decreased kidney function, cancer recurrence, and bone fractures. Furthermore, an adequate mycophenolic acid LT-AUC was associated with a decreased risk of allograft rejection, while cumulative corticosteroid exposure was not associated with allograft rejection.

Conclusion

This review analyzed a comprehensive set of articles and metrics that predict long-term outcomes of immunosuppressants in transplant patients. The wide variety of metrics studied highlight the lack of agreement on the best measures of drug exposure in transplant patients. Although certain metrics may demonstrate an association with outcomes, future studies should investigate the predictive power and validation of these metrics.