Next level of immunosuppression: Drug/immune monitoring

Abstract

1. Current immunological monitoring relies heavily on clinical judgment and therapeutic drug levels and does not adequately assess the functional or donor-specific immunosuppression (IS) status of recipients of liver transplantation (LT). 2. Trough levels of drugs are arbitrary and are more clinically relevant for preventing supratherapeutic or subtherapeutic dosing and blood concentrations and for more closely monitoring at-risk populations (children, the elderly, and patients with organ dysfunction). The AUC or the post-dose levels may be more precise, but they have not been used extensively by transplant centers. 3. Data on drug/immune monitoring specific to LT are fairly limited; therefore, clinical practice is often borrowed from experiences with nonhepatic transplantation (mainly renal transplantation). 4. The monitoring of drug levels in patients taking generic immunosuppressants is challenging because the formulations may change with each prescription. The monitoring of drug or antibody levels is not yet clinically available for biological therapies (induction, lymphocyte-depleting, and maintenance agents). 5. Polymorphisms in drug metabolism (cytochrome P450 and P-glycoprotein) may be useful in selecting the initial and maintenance dosages of immunosuppressants and in preventing complications from over or underimmunosuppression. 6. Future immune monitoring assays should be focused on genomic or immunological predispositions and on specific reactivities to donor antigens to guide the appropriate dosing and minimization of IS after LT.