In contrast,

pharmacodynamic (PD) monitoring examines the physiological effects of a drug rather than using the surrogate marker of drug concentration. Combining PD with PK monitoring has the potential to improve therapeutic drug dosing, thereby increasing efficacy and safety in an individual patient. The purpose of this review is to provide the clinician with an overview of the recent literature on the methodology and use of immune function Carfilzomib monitoring in the field of kidney transplantation. Both B and T lymphocytes have been implicated in the pathogenesis of acute and chronic allograft rejection. However, perhaps because T cells are the major targets of most immunosuppressant drugs, and B-cell effector mechanisms depend on T-cell help, T-cell biology has received significantly greater attention as a potential PD marker (Table 1, Fig. 1). T-cell assays can be broadly divided into two major categories: donor antigen specific or non-antigen specific.

Donor antigen specific assays involve stimulation of immune cells ex vivo with donor-derived mitogen such as donor lymphocytes. Non-antigen specific assays can be antigen independent find more (e.g. measurement of lymphocyte subsets), or assess the functional state of T cells following stimulation with a polyclonal stimulant (e.g. phytohaemagglutinin (PHA), concanavalin A, phorbol 12-myristate 13-acetate/ionomcyin and pokeweed mitogen). Although donor-derived stimuli may be more specific in determining immune reactivity to the allograft, the limited availability of donor cells precludes repeat testing in the clinical setting. As such, polygenic stimuli are more likely to be applied in routine clinical practice. Only non-antigen specific assays will be discussed further in this review. Additionally, detailed discussion of the techniques for each of these assays is beyond the scope of this paper (for this, see review by Najafian et al.36). Fluorescent-activated cell sorting (FACS) analysis is a simple and sensitive method that allows sorting and quantification of lymphocyte

subsets by fluorescent labelling of cell surface markers. Although a number of studies5,6 have shown Org 27569 that standard triple immunosuppressive regimens lead to significant reductions in the CD4+/CD8+ ratio in transplant recipients without effecting total lymphocyte number,5,6 there are only very limited and conflicting data linking lymphocyte subset counts with clinical outcomes. Although one study reported that decreased CD4 helper activity was associated with a lower risk of rejection, there was no relationship between the actual pre-transplant T or B-cell subset counts and acute rejection or 1-year graft function. However, the same study did show a correlation between elevated pre-transplant CD8+ suppressor-effector T-cell subset counts (CD8+CD11b+) and the occurrence of post-transplant infection.