title: How best to use tacrolimus (FK506) for treatment of steroid- and OKT3-resistant rejection after renal transplantation.
abstract: Nineteen patients with biopsy-confirmed ongoing acute rejection of renal allografts were converted from standard immunosuppression to FK506. Eight grafts showed vascular rejection and 11 had cellular rejection on biopsy. All patients had already received intravenous high-dose steroid treatment. Ten patients also had additional OKT3 rescue therapy. Initial FK506 doses were 0.13 +/- 0.06 mg/kg/day; the FK506 whole blood trough level after 3 days of treatment was 9.3 +/- 4.5 ng/ml. After conversion to FK506 all but four patients also received azathioprine, 1.5-2 mg/kg/day, and all patients received oral prednisolone. Concomitant with initiation of FK506, an anti-infective prophylaxis was prescribed, consisting of ganciclovir and trimethoprim/sulfamethoxazole. Sixteen out of 19 of the grafts (84%) were rescued successfully, including two grafts of patients already on hemodialysis at the time of conversion. Graft function of the responders improved from an average serum creatinine level of 364 +/- 109 mumol/L to 154 +/- 49 mumol/L. Of the patients receiving high-dose steroids alone prior to FK506 initiation, 8/9 responded to FK506 treatment, compared with 8/10 of those who had also received OKT3. During the mean follow-up of 35 weeks after conversion, no clinically apparent cytomegalovirus infection and no pneumonia were seen. Treatment with FK506 may successfully suppress ongoing acute rejection, even if antilymphocyte preparations have failed. FK506 can be used at a lower dose than so far recommended without impairing the antirejection potential. An additional anti-infective prophylaxis seems effective in preventing severe complications in the first months after rejection therapy.
authors.affiliation: Abteilung Nephrologie and Klinik für Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, Germany.
authors.forename: O K
authors.initials: OK
authors.lastname: Eberhard
authors.forename: V
authors.initials: V
authors.lastname: Kliem
authors.forename: K
authors.initials: K
authors.lastname: Oldhafer
authors.forename: H J
authors.initials: HJ
authors.lastname: Schlitt
authors.forename: R
authors.initials: R
authors.lastname: Pichlmayr
authors.forename: K M
authors.initials: KM
authors.lastname: Koch
authors.forename: R
authors.initials: R
authors.lastname: Brunkhorst
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016572:Cyclosporine; D016559:Tacrolimus