title: Induction immunosuppression with antilymphocyte globulin or OKT3 in cadaver kidney transplantation. Results of a single institution prospective randomized trial.
abstract: Improved cadaver kidney allograft survival rates, shorter duration of acute tubular necrosis, and a reduction in the incidence of rejection have been achieved using "quadruple sequential therapy"--AZA, prednisone, and antilymphocyte globulin (ALG) induction followed by the delayed addition of CsA. OKT3 has been shown to be effective in preventing and treating rejection, including steroid- and ALG-resistant rejection episodes. A single institution prospective randomized trial comparing ALG and OKT3 prophylaxis in first cadaver kidney allograft recipients was performed to assess their relative advantages and disadvantages. First cadaver kidney allograft recipients were prospectively randomized to receive 7 days of either ALG (n = 58) or OKT3 (n = 59) as part of a quadruple therapy protocol that included AZA, prednisone, and oral CsA. Patient characteristics, patient survival and causes of death, graft survival and causes of graft loss, incidence of and time to rejection and response to treatment, incidence of infections and their type, renal function, and antibody formation to ALG and OKT3 were examined. The 1-, 2-, and 3-year actuarial patient survival rates were 96% in the ALG group and 98% in the OKT3 group. The graft survival rates were 81.1%, 78.4%, and 78.4% in the ALG group and 84.1%, 78.7%, and 78.7% in the OKT3 group. In ALG-treated patients, 63% never had rejection, compared with 49% in the OKT3 patients (P = NS). In the ALG group 31% had a single rejection, 6% had 2 rejections, and none had 3 rejections, compared with 37%, 12%, and 2% in the OKT3 group. In the ALG group, 43% were steroid responsive compared with 65% in the OKT3 group (P = 0.08). There were 1.44 infections per patient in the ALG group compared with 0.76 in the OKT3 group (P = 0.0004). In the ALG group, 37% of patients developed CMV disease compared with 10% in the OKT3 group (P = 0.001). In donor-positive/recipient-negative patients, 8/10 (80%) in the ALG group developed CMV infection, of which 6 (75%) had severe or moderate CMV disease, compared with 2/15 (13%) patients in the OKT3 group (P = 0.002), of whom only one (6.7%) developed moderate disease. In donor-positive/recipient-positive patients, 8/23 (35%) in the ALG group developed CMV infection, of whom 5/8 (62.5%) developed severe or moderate disease compared with 1/21 (4.8%) in the OKT3 group (P = 0.02). Antibody formation to ALG and OKT3 occurred in 11% and 8% of patients, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: D W
authors.initials: DW
authors.lastname: Hanto
authors.forename: M D
authors.initials: MD
authors.lastname: Jendrisak
authors.forename: S K
authors.initials: SK
authors.lastname: So
authors.forename: C S
authors.initials: CS
authors.lastname: McCullough
authors.forename: T M
authors.initials: TM
authors.lastname: Rush
authors.forename: S M
authors.initials: SM
authors.lastname: Michalski
authors.forename: D
authors.initials: D
authors.lastname: Phelan
authors.forename: T
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000917:Antibody Formation; D000961:Antilymphocyte Serum / Q000494:pharmacology*; D002102:Cadaver; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007108:Immune Tolerance; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000494:pharmacology*; D011446:Prospective Studies; D013530:Surgical Wound Infection / Q000209:etiology
chemical_list: D000961:Antilymphocyte Serum; D016853:Muromonab-CD3