A 14-year experience with kidney transplantation.

Between November, 1962 and August, 1975, 668 kidney transplants were done in 556 consecutive patients at Denver, Colorado. The Denver experience has been divided into 7 periods of time, according to the conditions of care during each period. The results in related transplantation have changed little during the decade beginning in 1966. The results in unrelated transplantation have not materially changed since 1968. The long-term patient survival after related transplantation has been better than after cadaver transplantation. The results of transplantation in 57 children ages 3 to 18 years have been slightly better than the results of adult transplantation. The outcome of kidney transplantation and the feasibility of improving this therapy with present techniques are limited by our inability to accurately match each patient with the immunologically best donor and by our inability to precisely control the immune system of the recipient. Rejection is still the main reason for graft loss, and sepsis remains the main cause of patient mortality. More specific and less toxic means of achieving graft acceptance are needed before a higher level of patient service can be realized. However, even with the tools now available, thousands of recipients throughout the world have been returned to useful lives

Modulation of accelerated rejection of cardiac allografts in sensitized rats by anti-interleukin 2 receptor monoclonal antibody and cyclosporine therapy

LBNF1 cardiac allografts (Tx) are rejected within 36 hr in LEW rats sensitized with BN skin Tx 7 days earlier, compared to 8-day rejection in unmodified hosts. Treatment with cyclosporine or ART-18, an anti-interleukin 2 receptor (IL-2[R]) mAb monoclonal antibody, abrogates accelerated rejection and prolongs mean Tx survival to 42 days and 16 days, respectively. ART-18 given in concert with subtherapeutic dose of CsA extends survival to 25 days. These studies were designed to dissect the early mechanisms leading to ART-18 and/or CsA-mediated abrogation of accelerated Tx injury. No effect of concomitant mAb administration upon CsA trough levels was noted in Tx recipients conditioned with both modalities. The beneficial effect of ART-18+CsA treatment was also unrelated to CsA-induced diminished host responses to mAb, as shown by ELISA. In the biodistribution studies 125I labeled ART-18 accumulated preferentially into host lymphoid tissues and Tx itself and away from the blood. In animals that were concomitantly given 'cold' CsA, the clearance of labeled ART-18 from the blood increased further, as did mAb sequestration into the Tx. The sensitized hosts developed high titers of complement-dependent cytotoxic (CDC) antibodies, which peaked at the time of actual Tx loss. ART-18 or CsA alone inhibited CDC, whereas combined therapy decreased further the humoral effects of sensitization. The cell-mediated lymphocytotoxicity assay revealed a similar pattern. CsA, ART-18, and combination therapy each modulated the deposition of IgG, IgM, and C3 in Tx, as shown by immunohistology. However, only CsA or ART-18+CsA therapy abolished or markedly decreased elaboration of IL-2, interferon gamma, and tissue necrosis factor alpha. In conclusion: (1) the adjunctive low dose of CsA potentiates the inhibitory effects of ART-18 upon humoral and cellular responses, leading to accelerated rejection of cardiac Tx in presensitized rats; (2) the synergistic interaction between both modalities that results in the inhibition of lymphokine production is critical and correlates with long-term Tx survival; (3) the biodistribution patterns of mAb are important - an increased blood level of mAb does not necessarily translate into its higher therapeutic efficacy