title: Half dose of OKT3 is efficient in treatment of steroid-resistant renal allograft rejection.
abstract: Rejection episodes in renal allograft recipients are usually efficiently treated with high doses of intravenous methylprednisolone. Rejection therapy with OKT3 is often reserved for steroid-resistant episodes. However, the optimal dose of OKT3 in the treatment of steroid-resistant rejection is not known. Therefore, we randomized renal transplant recipients with steroid-resistant rejection to treatment with a standard daily intravenous dose of either 5 mg of OKT3 (n=15) or 2.5 mg of OKT3 (n=15) for 10 days. Circulating T cells (measured as CD2+ cells) were adequately and equally depleted in the two groups. Three grafts were lost due to rejection within the first 3 months following OKT3 administration, one in the 2.5 mg OKT3 group and two in the 5 mg OKT3 group. Two nonimmunologic graft losses occurred in the 2.5 mg OKT3 group. Median serum creatinine values were not different between the two groups, neither at the start (median values: 200 micormol/L in the 5 mg OKT3 group vs. 188 micromol/L in the 2.5 mg group) nor immediately after OKT3 rescue therapy (202 micromol/L vs. 185 micromol/L, respectively). Eight cytomegalovirus infections occurred in each group. Two re-rejection episodes occurred in the 5 mg OKT3 group and one occurred in the 2.5 mg OKT3 group. All responded to treatment. Function of the remaining grafts estimated by serum creatinine after a mean long-term follow-up of 18 months (range, 6-36 months) revealed no differences (185 micromol/L in the 5 mg OKT3 group vs. 170 micromol/L in the 2.5 mg OKT3 group). We conclude that OKT3 treatment of steroid-resistant rejections in renal transplant recipients is equally effective in daily doses of 2.5 mg and 5 mg with respect to reversal rate and long-term outcome.
authors.affiliation: Department of Internal Medicine, National Hospital, University of Oslo, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Midtvedt
authors.forename: A B
authors.initials: AB
authors.lastname: Tafjord
authors.forename: A
authors.initials: A
authors.lastname: Hartmann
authors.forename: T C
authors.initials: TC
authors.lastname: Eide
authors.forename: H
authors.initials: H
authors.lastname: Holdaas
authors.forename: K P
authors.initials: KP
authors.lastname: Nordal
authors.forename: B
authors.initials: B
authors.lastname: Draganov
authors.forename: G
authors.initials: G
authors.lastname: Sødal
authors.forename: T
authors.initials: T
authors.lastname: Leivestad
authors.forename: P
authors.initials: P
authors.lastname: Fauchald
mesh_terms: D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D003404:Creatinine / Q000097:blood; D003586:Cytomegalovirus Infections / Q000150:complications; D004306:Dose-Response Relationship, Immunologic; D004351:Drug Resistance; D005260:Female; D006084:Graft Rejection / Q000628:therapy*; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage*
chemical_list: D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D003404:Creatinine; D008775:Methylprednisolone