3 advances in monitoring immunosuppressive agents in 2020
Immunosuppression prevents and treats acute rejection and graft damage during kidney transplantation. The development immunosuppressive agents such as tacrolimus, cyclosporine, and mycophenolate minimized the rejection rate and improved short-term graft survival.
While the rejection rate has been reduced, it is not associated with increased long-term graft survival. Patients continue to experience chronic graft dysfunction, especially after a kidney transplant. As such, it is essential to administer immunosuppressant therapy to extend the life of the organ.
The immunosuppressants need careful monitoring to prevent rejection and toxicity. Over time, different methods have been developed to monitor drugs:
Therapeutic Drug Monitoring
During organ transplantation, doctors individualize patients’ drug therapy to obtain a balance between therapeutic efficacy and the subsequent adverse effects. Achieving this goal is not easy, given the patient variability in pharmacodynamics and pharmacokinetics.
Analytical techniques have since been developed as a result, the most common being therapeutic drug monitoring. This method uses the following criteria to examine candidates for the administration of immunosuppressants:
- Pharmacological response of the drugs should be difficult to distinguish from adverse effects.
- The drugs should have a narrow therapeutic index.
- There should be a relationship between the drug effect and concentration.
- There should be a poor relationship between drug and dose concentration.
While therapeutic drug monitoring has been a well-established technique for analyzing immunosuppressants, it does not predict their effects on immune cells. Pharmacodynamic monitoring has been developed as a result. It provides information about the biological effects each drug has on transplant patients.
Biomarkers relating to the pharmacodynamics effects of immunosuppressants are under investigation. The biomarkers should help identify patients at risk of developing acute rejection and infection and those eligible for immunosuppressive therapies.
Monitoring the Intracellular Concentrations of Immunosuppressants
The administration of ISP drugs requires the use of calcineurin inhibitors. They exert their effects in lymphocytes, which disrupts the normal T-cell activation.
Intracellular compartmentalization of peripheral blood mononuclear cells is another ISP monitoring procedure that has been developed to minimize this disruption. The technique is used to monitor calcineurin inhibitors to determine a patient’s ISP efficacy after an organ transplant procedure.
Advances in analytics like liquid chromatography and tandem mass spectrometry have also made it possible to use the measurements (intracellular concentrations of immunosuppressants) to predict clinical outcomes better in comparison with whole blood monitoring.