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Tolerance is the so-called "Holy Grail" of transplantation, but achieving this state is proving a major challenge, particularly in the clinical setting. Even in rodents, the definition of true transplant tolerance is not applicable to many models, with late graft damage often occurring despite long-term graft survival. Hence the term "operational tolerance," based more on graft function and absence of exogenous immunosuppression, is being adopted. Although the most sought-after goal in this field is to intentionally induce this state in a controlled manner, translating protocols across species from rodents to the clinic, the current literature demonstrates that this is proving a formidable task. A complementary approach is to address transplant tolerance from a different angle, by studying tolerance-like phenomena that occur "unintentionally" in transplant patients after immunosuppressive drug weaning. Such spontaneous operational tolerance, which can take place after years of immunosuppression, is rare in kidney transplant recipients. However, determining exactly how this state arises and how it can be detected may make it possible to induce it in a greater number of patients and then to return to the drawing board to rationally design protocols that have a greater chance of clinical success. Moreover, the study of such patients should help in the identification of biomarkers of low immunological risk that could be used to select patients for potential weaning. Collaborative efforts through international networks, together with the application of newer and more powerful technologies to diagnostic, prognostic, and mechanistic research, may help transplanters to achieve this goal.

In order to assess the immunosuppressive potentials of 15-deoxyspergualin (15-DS) in a preclinical experiment, heterotopic cardiac (n = 27, group I) and classic renal (n = 25, group II) allotransplantations were performed in Chacma baboons. The following immunosuppressive regimens were applied: Groups IB and IIB were treated with 15-DS alone (4 mg/kg/day) for p.o. days 0-9. Groups IC and IIC were treated with cyclosporine A (10-40 mg/kg/day) for p.o. days 0-30. Groups ID and IID received a combination of 15-DS (for p.o. days 0-9) and CsA (for p.o. days 0-30). Groups IA and IIA served as control and received no medication. The mean graft survival was 11.0 days for group IA, 28.2 days for group IB (P less than 0.05; IB vs. IA), 32.4 days for group IC, and 43.1 days for group ID (P less than 0.025; ID vs. IA). After renal transplantation, the corresponding figures were 12.3 days for group IIA, 8.5 days for group IIB, 30.4 days for group IIC and 148.9 days for group IID (P less than 0.025; IID vs. IIA). After cardiac and renal transplantation, acute rejection was the main cause of graft failure. Treatment-related side effects, mainly gastrointestinal complications, were observed only in primates, who were treated with 15-DS alone. After cardiac transplantation, permanent graft non-reactivity was not achieved, but a delayed rejection occurred within a mean of 21.8 days after immunosuppression had been stopped. Following renal transplantation, graft nonreactivity was also not achieved in groups IIB and IIC. In group IID, however, 4 of 8 animals (50%) were graft-tolerant 340, 256, 244, and 164 days after treatment discontinuation. Thus, the combination of 15-DS and CsA led to a significant prolongation of graft survival in both groups. Long-term nonreactivity was achieved only after renal transplantation, when initially treated with 15-DS and CsA.

Seventy-four recipients of related donor renal allografts were tested for the presence of cellular immunity to specific donor lymphocyte antigens using the direct migration inhibition factor (MIF) assay. Responses on the assay fell into one of the following three statistically distinct groups: (1) greater than 20% inhibition of macrophage migration, (2) nonresponsiveness, +/- 10% of control migration, and (3) greater than 12% stimulation of macrophage migration. Migration stimulation was shown to be reproducible and to correlate well with a very benign post-transplant clinical course. The production of migration stimulatory factor appears to be an immunological response analagous to the production of migration inhibition factor.

Transplantation is now an acceptable mode of therapy for end stage renal disease. Increased survival rates and acceptance of older recipients have resulted in an increased frequency of outlet obstruction in the male recipient. Reviews of urological complications in renal allotransplantation have failed to emphasize this clinical entity. We present 3 patients, each emphasizing a different facet in the natural history of outlet obstruction in the male recipient of a renal allotransplant. The rationale for aggressive investigation of outlet obstruction is emphasized.

Observation probablement unique: grossesse non soupconnee chez une malade de 18 ans sous hemodialyse, transplantation d'un rein de sa mere; au cours de l'operation la grossesse est constatee. Elle evolue normalement malgre les traitements immunode-presseurs et 1 seule hemodialyse est necessaire. L'enfant ne presente que des troubles sans relations avec l'etat renal de la mere ou les traitements qu'elle recoit

Current progress in the field of renal allotransplantation may make this experimental modality a commonplace therapeutic procedure in medical centers throughout the country. The problems of allograft rejection far outweigh technical difficulties with the vascular anastomoses. This is not true, however, with ureteral reconstitution. As the ability to counteract the early rejection crisis improves, the morbidity and complications resulting from ureteral surgery become manifest. Ureterocutaneous fistulae are common complications and their incidence has prompted the development of several new techniques, some hitherto untried in clinical surgery. Starzl 1 has advocated a seromuscular ureteroureteral anastomosis with fine silk which in his hands and others has given excellent results. 2 Leadbetter has reported a pyeloureteric anastomosis with equal success. 3 The Politano-Leadbetter procedure 4 has been employed in many centers with satisfactory results. The variety of surgical operations utilized attests to the frequency of problems encountered. Since it is often difficult to

Serial determinations of plasma erythropoietin and renin activities and mean arterial blood pressure were done in five dogs before and after renal allotransplantation. Throughout the experiment, the animals were given 154 mEq of NaCl per day, starting 1 week before transplantation. No immunosuppressive therapy was given. Onset of immunological rejection was determined by daily measurement of endogenous creatinine clearance. Arterial pressure and plasma erythropoietin concentration increased markedly at the time of rejection, with the curves for the two variables closely paralleling each odier in all animals. Serial determinations of plasma volume done in two of the dogs did not show any significant change at the time when hypertension appeared. Plasma renin activities remained very low throughout the experiments, indicating that even with the vascular lesions of rejection renin release is still subject to normal control mechanisms. It is concluded that elevated plasma renin activity is not an essential causal factor of the hypertension which occurs with renal allograft rejection. Since it is possible to suppress renin release without substantially inhibiting erythropoietin release, different stimuli appear to cause release of these substances.