REVERSAL OF ACCELERATED RENAL-ALLOGRAFT REJECTION WITH FK-506

Although FK 506 has been shown to effectively reverse refractory renal allograft rejection, its ability to reverse accelerated renal allogra ft rejection as a primary agent has not been specifically addressed. H erein evidence of the ability of FK 506 to reverse accelerated renal a llograft rejection is presented. A 16-yr-old highly sensitized (PRA 75 %) male underwent a second cadaveric renal transplant procedure. Despi te induction immunosuppression with ATGAM, cyclosporine, azathioprine, and corticosteroids, a marked elevation in serum creatinine (1.6-->2. 1 ng/dl) and reduction in urine output (4000 ml/d-->1000 ml/d) were ob served on the sixth post-transplant day. Renal allograft biopsy perfor med at that time revealed typical features of accelerated rejection in cluding neutrophil margination in glomerular and interstitial capillar ies, and C3, IgG, and fibrin deposition in glomerular and interstitial capillaries (by immunofluorescence). FK 506 therapy was promptly inst ituted and ATGAM therapy discontinued. Serum creatinine peaked within 3 d of FK 506 therapy (2.5 mg/dl) and subsequently progressively dropp ed to 1.2 mg/dl. Repeat biopsy on FK 506 treatment day 12 revealed mar ked histologic improvement. Renal function remains excellent (1.3 mg/d l) 18 months after initiation of FK 506 therapy, and recurrent rejecti on has not been observed. This experience provides evidence that FK 50 6 therapy may effectively reverse accelerated renal allograft rejectio n, and that it provides a means for treating antibody-mediated mechani sms of allograft rejection.