cyclosporine + tacrolimus (University of Minnesota)

In the context of the KADWORC clinical trial (NCT01492894), 'cyclosporins + tacrolimus' refers to the calcineurin inhibitor (CNI) class of immunosuppressants, specifically cyclosporine and tacrolimus. These small-molecule drugs are used to prevent organ rejection in transplant recipients by inhibiting calcineurin (protein phosphatase 2B). Cyclosporine binds to cyclophilin, while tacrolimus binds to FK506-binding protein 12 (FKBP12); both complexes then inhibit calcineurin's phosphatase activity. This prevents the dephosphorylation of the nuclear factor of activated T-cells (NFAT), thereby blocking the transcription of interleukin-2 (IL-2) and subsequent T-cell activation. The KADWORC trial, sponsored by the University of Minnesota, investigated whether a 50% dose reduction of these CNIs was superior to converting patients with chronic kidney graft dysfunction to sirolimus, though the study was ultimately withdrawn due to low enrollment.

Brand names

SandimmuneNeoralPrografAstagraf XLEnvarsus XRGengraf

Other names

calcineurin inhibitorsCNIscyclosporine and tacrolimus