FK506 in Solid Organ Transplantation

Abstract

Summary: FK506 (Prograt) is a new immunosuppressive agent. recently approved for use in solid organ transplants. The first use of FK506 was for the indication of refractory liver allograft rejection. This revealed a marked ability to reverse ongoing rejection. even in cases where chronic changes were observed. Between 50 and 70% of patients converted to FK506 had shown improvement. In long-term follow-up of patients with chronic rejection. 75% of patients were still alive at 3 years following FK506 conversion. and 65% of liver allografts were still functioning. FK506 has been compared to cyclosporine in primary liver transplantation. In the three randomized trials. freedom from rejection was statistically greater in the FK506-treated group, as compared to the cyclosporine-treated group. By intent-to-treat analysis, the patient and graft survival in the FK506 group was the same or better than the cyclosporine group. The good results in the cyclosporine limb was due. in part, to the ability of FK506 to treat rejection in the cyclosporine group. Freedom from steroid use, and the lower incidence of hypertension, were prominent features of FK506 patients. FK506 has been used for rescue of rejecting kidney allografts, with results similar to the liver transplant trials. When used as primary immunosuppression. FK506 was shown to be effective. as measured by graft survival. FK506-based immunosuppression has also been used in primary heart transplantation. as well as for primary adult pulmonary transplantation. Results from these small series of patients are equally encouraging. The results . of these studies suggest that FK506 is effective for solid organ transplantation. Both FK506 and cyclosporine administration have been associated with side effects. many of which are similar. and some of which are peculiar to a given organ transplant. Key Words: Tacrolimus-FK506-Solid organ transplantation. (1-4). The first clinical use of FK506 was for the indication of uncontrolled liver allograft rejection. which was therefore considered treatment failure of conventional immunosuppression (5-11). The results of this experience revealed a marked ability to reverse ongoing rejection, even in cases where chronic changes were observed. Between 50 and 70% of patients treated by FK506 (Prograt), a macrolide antibiotic produced by the fungus Streptomyces tsukubaensis is a new immunosuppressive agent 592conversion to FK506 had both clinical and histopathologic improvement. In a recent long-term follow-up of 113 patients with chronic rejection. 75% of patients were still alive at 3 years following FK506 conversion, and 65% of liver allografts were still functioning (8).Following an initial experience with FK506 as primary immunosuppression following liver transplantation at the University of Pittsburgh (12,13), FK506 has been compared to cyclosporine in primary liver transplantation, in randomized, nonblinded studies. At the University of Pittsburgh, low-risk candidates were randomized to FK506 with steroids as compared with cyclosporine...

Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients

“…Tacrolimus has also been successfully used in the treatment of chronic rejection, as rescue therapy for SRR, and as an alternative immunosuppressant for treatment of CyA-related adverse effects [8,16,19,201. Tacrolimus is associated with numerous side effects many of which, however, are similar to those of CyA.…”

Hypertension in thoracic transplant recipients

“…106 A lower incidence of hypertension was noted in an adult liver transplant population. 107 In the 2-year follow-up data of the European multicentre tacrolimus liver study, hypertension was less common in the tacrolimus (28%) when compared to the cyclosporin (40%) treated group. 108 Textor found than 4 months after liver transplantation, 4/14 (28%) of liver transplant patients treated with tacrolimus and prednisolone developed hypertension compared to 25/32 (78%) in a group treated with cyclosporin and prednisolone.…”

Affinity Maturation of Tacrolimus Antibody for Improved Immunoassay Performance

“…Tacrolimus, a macrolide immunosuppressant produced by the bacterium Streptomyces tsukabaensis (1 ), is used for the prevention of organ rejection (2,3 ) by preventing T-lymphocyte activation (4 ). Toxicity concerns (5 ) dictate patient monitoring, and a variety of different diagnostic immunoassays are commercially available (6 ).…”