title: FK506 "rescue" for resistant rejection of renal allografts under primary cyclosporine immunosuppression.
abstract: Seventy-seven patients with ongoing acute rejection on initial CsA therapy were converted to FK506 to attempt graft salvage. Fifty-nine patients had undergone primary transplantation and 18 had been retransplanted; there were 52 cadaveric and 25 living-donor transplants. The indications for conversion to FK506 were ongoing, biopsy-confirmed rejection in all patients, including vascular rejection in 20. The median interval to rescue was 2 months (range 2 weeks to 36 months) after transplantation. Sixty-one of the 77 patients (79%) had already received one or more courses of an antilymphocyte preparation (OKT3: n = 33; ALG or ATG: n = 1; OKT3+ALG/ATG: n = 27). Of the 77 patients, 57 (74%) have been successfully rescued and still have functioning grafts with a mean follow-up of 14 months, with a mean serum creatinine of 2.35 +/- 0.97 mg/dl. Eighteen patients were already dialysis-dependent at the time of conversion to FK506; of these, 9 (50%) were successfully salvaged and have a mean serum creatinine of 2.3 mg/dl. Of the 61 patients previously treated with antilymphocyte preparations, 48 (79%) were rescued. In those salvaged, prednisone doses have been lowered from 22.2 +/- 7.2 mg/day preconversion to 7.5 +/- 5.6 mg/day postconversion, and 12 patients are on FK506 monotherapy. In nondiabetics, mean serum glucose was 101.4 +/- 20.5 mg/dl preconversion and 93.2 +/- 22 postconversion (P = 0.07), uric acid 7.3 +/- 2.3 and 7.1 +/- 1.5 mg/dl (P = 0.53), and triglycerides 199.2 +/- 101.6 and 167.2 +/- 106.4 mg/dl (P = 0.06). Cholesterol levels were significantly lower following FK conversion (207.7 +/- 46.5 mg/dl pre. vs. 188.3 +/- 39.7 post., P = 0.007). FK506 is capable of salvaging renal allografts with ongoing acute rejection on CsA therapy, even when antilymphocyte preparations have been ineffective.
authors.affiliation: Division of Urologic Surgery and Renal Transplantation, University of Pittsburgh Medical Center, Pennsylvania 15213.
authors.forename: M L
authors.initials: ML
authors.lastname: Jordan
authors.forename: R
authors.initials: R
authors.lastname: Shapiro
authors.forename: C A
authors.initials: CA
authors.lastname: Vivas
authors.forename: V P
authors.initials: VP
authors.lastname: Scantlebury
authors.forename: P
authors.initials: P
authors.lastname: Rhandhawa
authors.forename: G
authors.initials: G
authors.lastname: Carrieri
authors.forename: J
authors.initials: J
authors.lastname: McCauley
authors.forename: A J
authors.initials: AJ
authors.lastname: Demetris
authors.forename: A
authors.initials: A
authors.lastname: Tzakis
authors.forename: J J
authors.initials: JJ
authors.lastname: Fung
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus