Woodle ES, Thistlewaithe JR, Gordon JH, Laskow D, Deierhoi
MH, et al.
A multicenter trial of FK506 (tacrolimus) therapy in refractory
acute renal allograft rejection: A report of the tacrolimus
kidney transplantation rescue group
(Sep) 62:594-599 1996
Control of acute cellular rejection has clear long term renal graft survival
benefit. This multicenter trial of 73 kidney transplant patients with
demonstrated acute rejection included 59 who were refractory to
antilymphocyte therapy (OKT3 and ATGAM). All patients had been
treated and failed traditional corticosteroid and cyclosporin treatment and
89% were receiving azathioprine. Intervention consisted of oral
administration of tacrolimus 0.15-0.3 mg/kg/day. Steroids were
continued but cyclosporin was stopped prior to intervention.
blood IMx assays demonstrated FK506 levels of 15 +/- 9.9 ng/ml on day
7 and 9.4 +/- 5.1 ng/ml at one year (the end of the follow up period). With
this approach, 78% of patients had improvement by biopsy or a 10%
decrease in serum creatinine. An additional 11% had stabilization of
renal function. Not surprisingly, there was a linear increase in risk of
graft loss associated with a higher pre-treatment creatinine.
Approximately one in four patients had side effects, mostly with
headache, tremor, or GI distress.
Comment: This study builds upon earlier work
from Pittsburgh, Cincinnati, and other centers supporting the role of
tacrolimus "rescue" in acute renal allograft rejection. No specific
explanation has been offered for this effect. It should be noted that this
trial was conducted in conjunction with Fujisawa USA, Inc., the makers
(Sri Narsipur, MD, SUNY-HSC at Syracuse, NY)