Research Award Recipients

Cell-based immunosuppression reduction for kidney transplant recipients: a pilot study

Co-applicant(s): Héloïse Cardinal, Julie Ho

Lay Abstract

Background: Immunosuppression is essential for the treatment of kidney transplant recipients and patients with immune-mediated diseases. Unfortunately, patients taking immunosuppressants may experience undesirable side effects, the most important being serious infections and cancers. Currently, patients are mostly prescribed immunosuppressants in a “one size fits all” fashion and adjusted following the occurrence of events.

Purpose: Similar to the measurement of blood pressure to adjust anti-hypertensive drugs, we need a clinical tool to adjust the immunosuppressants. Such a tool would allow identifying patients with lower immune reserve, thus at higher risk of infection and cancer. Over the last 10 years, we developed a cell-based assay that measures the response capacity of the immune system. This assay can predict the risk of serious infections and cancer. We recently validated, in a multicenter cohort of 5 Canadian centers, that this test can classify patients at low (11%), intermediate (18%), and high risk (30%) of events. We now propose to test whether providing the results of this tool to patients and caregivers will lead to a safe reduction in immunosuppression in patients at high risk.

Method: We will conduct a pilot interventional trial. In the intervention group, we will test the immune response every 3 months and provide the patient and the clinical team the risk score of adverse events. In the control group, patients will be managed as usual, without a specific tool to inform on the risk of adverse events.

Anticipated outcomes: We anticipate that patients at high risk may decide to reduce their immunosuppression. Because the test will identify those with a lower immune response, we expect that this guided immunosuppression reduction will be safe, with no increase in rejection rate. Furthermore, we expect that this guided reduction of immunosuppression will result in lower rates of adverse events.

Patient engagement: By design (both the patient and the clinical team will receive the results of the test), all the participants will be actively engaged in the process during the study. The reason is that by examining immunosuppressant doses at the end of the study, we will directly measure how the information provided by the test influenced treatment. At the end of the study, patients will be asked to comment on their experience. Relevance: The novelty of this project is that it deals with over-immunosuppression. Lowering the immunosuppression will, to a certain extent increase the risk of rejection. However, the risk of rejection nowadays is very low given the strong immunosuppression prescribed. Paradoxically, the mortality in kidney recipients is now driven more by adverse events than by rejection. We want to get a better balance between the benefits and the adverse effects of immunosuppression.

Conclusion: We may have reached a point where immunosuppression is too high in some patients. Personalizing immunotherapy should help to get the benefits of transplantation, while minimizing the occurrence of serious adverse events. This knowledge could be useful not only to kidney transplant recipients, but to any patient receiving immunosuppressants.