Trends in Precision Medicine and Pharmacogenetics as an Adjuvant in Establishing a Correct Immunosuppressive Therapy for Kidney Transplant: An Up-to-Date Historical Overview
A review arguing that much of the wide patient-to-patient variability in immunosuppressant handling, and therefore much rejection and toxicity, traces back to genetic differences in drug-metabolising enzymes and transporters. It makes the case for validated sequencing-based pharmacogenetic panels to guide dosing in kidney transplant recipients.
Background
Kidney transplantation is the treatment of choice for end-stage kidney disease, but the host immune response remains the principal challenge and a frequent cause of graft rejection. Immunosuppressive agents are now fully integrated into clinical management, yet dosing them correctly remains difficult.
Key findings
The review attributes the considerable inter- and intra-patient variability in immunosuppressant pharmacokinetics and pharmacodynamics chiefly to the polymorphic nature of genes encoding xenobiotic-metabolising enzymes, transport proteins, and in some cases the drug targets themselves. These genetic differences influence drug metabolism and distribution, producing either toxicity or reduced efficacy.
Clinical implications
The authors argue for research and investment in validated next-generation-sequencing-based commercial panels for pharmacogenetic profiling of kidney transplant recipients, with the goal of implementing precision medicine to optimise immunosuppressive therapy, improve graft survival, and improve patient outcomes.
Category
Transplant
Source
International Journal of Molecular Sciences
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