HDCN Article Review/Hyperlink

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

Transplantation (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 biopsy 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.

Whole 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 of tacrolimus. (Sri Narsipur, MD, SUNY-HSC at Syracuse, NY)