title: Tacrolimus rescue therapy for renal allograft rejection--five-year experience.
abstract: Over the 5 year period from 7/14/1989 until 5/24/1994, we have attempted graft salvage with tacrolimus conversion in a total of 169 patients (median age 33 years, range 2-75 years) with ongoing rejection on baseline CsA immunosuppression after failure of high dose corticosteroids and/or antilymphocyte preparations to reverse rejection. The indications for conversion to tacrolimus were ongoing, biopsy confirmed rejection in all patients. The median interval to tacrolimus conversion was 2 months (range 2 days to 55 months; mean 4.3+/-2.6 months) after transplantation. All patients had failed high dose corticosteroid therapy and 144 (85%) of the 169 patients had received at least one course of an antilymphocyte preparation plus high dose corticosteroid therapy prior to conversion. Twenty-eight patients (17%) were dialysis-dependent at the time of conversion owing to the severity of rejection. With a mean follow-up of 30.0+/-2.4 months (median 36.5 months, range 12-62 months), 125 of 169 patients (74%) have been successfully rescued and still have functioning grafts with a mean serum creatinine (SCR) of 2.3+/-1.1 mg/dl. Of the 144 patients previously treated with antilymphocyte preparations, 117 (81%) were salvaged. Of the 28 patients on dialysis at the time of conversion to tacrolimus, 13 (46%) continue to have functioning grafts (mean SCR 2.15+/-0.37 mg/dl) at a mean follow-up of 37.3+/-16.7 months. In the 125 patients salvaged, prednisone doses have been lowered from 28.0+/-9.0 mg/d (median 32, range 4-60 mg/d) preconversion to 8.5+/-4.1 mg/d (median 12 mg/d, range 2.5-20 mg/d) postconversion. Twenty-eight patients (22.4%) are currently receiving no steroids. This 5 year experience demonstrates that tacrolimus has sustained efficacy as a rescue agent for ongoing renal allograft rejection. Based on these data, we recommend that tacrolimus be used as an alternative to the conventional drugs used for antirejection therapy in renal transplantation.
authors.affiliation: Pittsburgh Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Jordan
authors.forename: R
authors.initials: R
authors.lastname: Naraghi
authors.forename: R
authors.initials: R
authors.lastname: Shapiro
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.forename: C A
authors.initials: CA
authors.lastname: Vivas
authors.forename: V P
authors.initials: VP
authors.lastname: Scantlebury
authors.forename: H A
authors.initials: HA
authors.lastname: Gritsch
authors.forename: J
authors.initials: J
authors.lastname: McCauley
authors.forename: P
authors.initials: P
authors.lastname: Randhawa
authors.forename: A J
authors.initials: AJ
authors.lastname: Demetris
authors.forename: J
authors.initials: J
authors.lastname: McMichael
authors.forename: J J
authors.initials: JJ
authors.lastname: Fung
authors.forename: T E
authors.initials: TE
authors.lastname: Starzl
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate; D016559:Tacrolimus / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000305:Adrenal Cortex Hormones; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011241:Prednisone; D016559:Tacrolimus