TREATMENT OF ACUTE GLOMERULAR REJECTION WITH FK-506

Acute glomerular rejection is a distinct pathologic subtype of rejecti on that is often refractory to standard therapy and is associated with significant risk of graft lass. Both cellular and humoral mechanisms have been shown to be involved in the pathophysiology of acute glomeru lar rejection. FK506, because of its ability to inhibit both cellular and humoral mechanisms of rejection provides a theoretically attractiv e approach for treating acute glomerular rejection, This initial exper ience with FK 506 treatment of acute glomerular rejection occurred in a 58-yr-old woman who received a 0 AB, 2 DR-match cadaveric renal tran splant. A renal allograft biopsy performed on post-transplant day 77 f or renal dysfunction (serum creatine 1.3-->1.8 mg/dl) revealed moderat e cellular and vascular rejection. Corticosteroid therapy provided a t ransient improvement in renal function; However. a repeat biopsy 7 d l ater revealed acute glomerular rejection with immunohistologic evidenc e of antibody-mediated rejection (immunoglobulin and complement deposi tion in glomerular capillaries). FK 506 therapy uas instituted and pro vided prompt reversal of the acute glomerular rejection as determined by serial renal allograft biopsies. One year later, recurrent rejectio n has not been observed, and good renal function is present. (Current serum creatine 1.7 mg/dl, creatine clearance 35 ml/min/m(2), and 24 h urinary protein 230 mg.) Successful corticosteroid withdrawal has been achieved, and current immunosuppressive therapy consists only of FK 6 06 and azathioprine, This experience indicates that FK 506 can provide effective therapy for acute glomerular rejection, and that simultaneo us treatment with plasmapheresis and an antilymphocyte antibody prepar ation may not be necessary, This experience also provides further evid ence of the ability of FK 506 to inhibit antibody-mediated rejection p rocesses.