FK-506 THERAPY FOR REFRACTORY RENAL-ALLOGRAFT REJECTION - LESSONS FROM LIVER-TRANSPLANTATION

FK 506 has proven to be an effective immunosuppressive agent in liver transplantation, but its role in renal transplantation remains to be d efined. Since the initial availability of FK 506 for treatment of refr actory renal allograft rejection, we have applied an aggressive approa ch consisting of institution of rescue therapy at an early point in th e rejection process combined with assiduous monitoring of FK 506 blood levels and the histologic response to therapy. A total of 17 adult pa tients were treated for refractory renal allograft rejection with this approach. Median follow-up was 9 months post-initiation of FK 506 the rapy. Median time to first rejection was 26 d post-transplant, and med ian time to FK 506 rescue therapy was 113 d post-transplant. Sixteen o f 17 patients received either ATGAM or OKT3 induction therapy. Prior t o FK 506 rescue therapy, patients received the following antirejection therapy: corticosteroids 40+21 mg/kg (prednisone or Solumedrol), OKT3 (median 14 d), ATGAM (3 patients, 14 d each). FK 506 rescue therapy w as successful in reversing the rejection process in all 17 patients. F ifteen patients (88%) demonstrated rapid reversal of rejection (i.e. r eversal within 14 d), whereas three patients demonstrated delayed reve rsal. Nine month actuarial patient and graft survivals were 92% and 84 %. When censored for documented noncompliance, nine month actuarial gr aft survival was 92%. Good long-term renal function was observed (pre- FK 506 baseline creatinine 2.1+/-0.5 mg/dl, current serum creatinine 2 .1+/-0.6 mg/dl. Six recurrent rejection episodes occurred in 5 patient s (29%) with a median time to recurrent rejection of 59 d post-initiat ion of FK 506 rescue therapy. Each recurrent rejection episode was suc cessfully treated by corticosteroids and/or increased FK 506 dose. CMV disease and lymphoma were not observed. Histologic evidence of FK 506 nephrotoxicity (hyaline necrosis in preglomerular arterioles) was obs erved in 6 patients 30% (median time to diagnosis 49 d). FK 506 blood levels (whole blood TDX) between 10 and 20 ng/ml provided effective re versal in most patients. Current FK 506 dose and blood levels are 0.18 +/-0.09 mg/kg/d and 7+/-2 ng/dl). FK 506 rescue therapy also allowed a ggressive reductions in prednisone dose: (mean current prednisone dose 0.08+/-0.05 mg/kg/d). In conclusion, an aggressive approach toward FK 506 rescue: 1) provides prompt, effective reversal of refractory rena l allograft rejection, 2) good long-term renal allograft function, 3) balanced immunosuppression with respect to recurrent rejection, opport unistic infection and PTLD, 4) acceptable toxicity, and 5) aggressive reduction in corticosteroid dosing, Based on these findings, FK 506 re scue therapy is now the treatment of choice in our program for renal a llograft rejection episodes that occur following antilymphocyte antibo dy therapy.