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One thousand and eighteen patients who received first cadaveric renal transplants (age 18–80 yr) at the University of Toronto from 1981–1991 were reviewed in order to compare the results of patients older than 55 years of age (n=251) with the rest of the group (n=767). One- and 5-year graft survival were significantly lower in patients over 55 years of age compared to younger patients; 74% vs. 82% at one year and 49% vs. 75% at 5 years (p

A total 166 first cadaveric renal allograft recipients were randomly assigned to receive either rabbit antithymocyte serum (RATS) (n = 83) or OKT3 (n = 83) for 10 to 14 days after transplant as prophylaxis against rejection. Both groups were similar with respect to age, sex, donor age, diabetes, time on dialysis, panel-reactive antibody, HLA matching, and transfusion before transplantation. All patients were followed for 1 year after transplantation. A comparison of the rejection rates between the 2 groups of patients showed that patients receiving OKT3 had a rate of first rejection 1.87 times higher than those receiving RATS (95% confidence interval 1.18-2.8, P = 0.007). Twenty-five steroid-resistant rejections occurred in OKT3-treated patients as compared with 12 in the RATS-treated group (P < 0.05). There was no significant difference in early or late renal function between the 2 groups of patients. Actuarial 1-year graft survival for the RATS group was 78% and for the OKT3 group, 80.7% (P = NS). Actuarial 1-year patient survival was similar: 89.5% in the RATS group and 94.6% in the OKT3 group (P = NS). Total hospitalization time was 29.8 +/- 19.9 days for RATS vs. 39.5 +/- 22.1 days for those treated with OKT3 (P < 0.006). A number of infections were observed but there were no significant differences between the groups. We conclude that RATS provides better prophylaxis than OKT3 in first cadaveric renal transplants because it is associated with fewer rejection episodes, less hospitalization, and no additional morbidity or mortality.

Transplantation has become the treatment of choice for many chronic and debilitating diseases. Generally, the primary endpoints in evaluating therapy are graft and patient survival time. However, an important secondary outcome is the number of "rejection episodes" experienced by study patients. This response has a distinctive statistical character. That is, it is a categorical variable since it assumes only a small number of integer values, but it is measured on a ratio-level scale since the ratio of any two values is scientifically meaningful. Historical methods for analyzing this endpoint, for example, t tests, logistic regression and Kaplan-Meier analysis, have failed to take these characteristics into account. In this study, we investigated statistical procedures for analyzing the number of rejection episodes arising during the first three months posttransplant. Data compiled by the Multiple Organ Retrieval and Exchange (MORE) of the Province of Ontario were used for this purpose. It was found that assumptions underlying normal distributional techniques were not satisfied by these data. An alternative model based on Poisson regression models was considered and was shown to provide an adequate fit.

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Donor-specific alloantibody was monitored in recipients of 81 renal allografts by 51Cr release assays. Complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity were both followed. In addition to the conventional lymphoid target cells nonlymphoid target cells, namely fibroblasts from the donor, were used. Although antibody against donor lymphoid cells was found more frequently, associations with graft loss and with rejection were greater with antibody against fibroblasts. The superior association of antibody against fibroblasts with clinical events suggests that wider use of nonlymphoid target cells would be of value in studies of alloantibody responses in renal transplant recipients.

Procoagulant activity (PCA) of leukocytes of renal transplant recipients was studied. This material, which activates coagulation, has previously been shown to be released from macrophages after they interact with mitogen-stimulated or antigen-stimulated T lymphocytes. Under endotoxin-free conditions, PCA of peripheral blood leukocytes, incubated for 90 min in tissue culture, was elevated in postoperative transplant recipients and in many transplant patients tested around the time of a rejection episode. The response to lipopolysaccharide added during culture was also increased in these populations. The PCA response was factor-VII-dependent when tested with washed peripheral blood mononuclear cells (PBMC), but was factor-VII-independent when tested with unwashed PBMC in their original culture medium. The results indicate a possible link between immunologic events and coagulation in transplant recipients.

We performed a multicenter study to investigate the problem of cadaver kidney transplants that never achive function, or that recover after a period of delayed function, and we used multivariate techniques to model the results. Sixty-nine patients who received cadaver kidney transplants that never functioned (NF) were compared with 69 kidney recipients with early graft function (EF), and 69 with delayed but recovering graft function (DF), magtched for transplant hospital and time. The results were analyzed using an unconditional logistic regression model. Risk factors for never-function transplants compared to immediate-function transplants were as follows: previous failed transplant, no polyclonal antilymphocyte globulin (ALG) prophylaxix, increasing anastomosis time, decreasing donor blood pressure, and priod transfusions in first but not subsequent transplant recipients. When technical failures were excluded, 88% of NF grafts displayed severe rejection, suggesting that rejection in a poorly functioning kidney is the principal cause of the NF outcome. risk factors for delayed function compared to immediate function were these: in creassing anastomosis time, no ALG, increasing total cold ischemia time, duration of end-stage renal disease (ESRD), and male sex. Thus ischemic and immunologic risk factors contributed to the DF and NF outcomes. This study suggests that efforts to reduce the delayed and never-function outcomes should be directed to the use of ALG prophylaxis and to the reduction of cold ischemia and anastomosis times, particularly in recipients who have lost a previous transplant.

Adsorbed measles and poliomyelitis vaccines of monkey kidney tissue culture origin sensitize guinea pigs to protein components of the tissue culture, as shown by the passive cutaneous anaphylactic test. Unadsorbed vaccines are not sensitizing, and there is a correlation between the production of anaphylactic antibodies in guinea pigs by different vaccines and their ability to sensitize infants to a subsequent injection of attenuated measles virus vaccine.