Donor pretreatment as an adjunct to cadaveric renal transplantation--update 1979.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R D Guttmann.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Post-transplant hypertension has been observed in 98 renal allograft recipients who had good renal function and whose follow-up was more than 15 months. The role of the original diseased kidneys as well as the role of the renal pressor system was studied with emphasis on late hypertension. Post-transplant hypertension was found to be a multifactorial phenomenon with frequency decreasing as a function of prolonged graft survival. Renal artery stenosis was an infrequent but significant cause of hypertension and was found in 10 of 29 arteriograms performed. Renin studies performed in 34 hypertensive patients and in a control group of 11 recipients showed that elevation of plasma renin activity and of plasma aldosterone level is frequent but difficult to interpret, particularly when a renal artery stenosis is observed. These investigations may be useful in recognizing the role of retained diseased kidneys in sustaining hypertension. Plasma aldosterone was found elevated in nearly all of the patients. The role of corticosteroids and the similarity of post-transplant hypertension, in some cases, with the one kidney model of experimental hypertension are discussed.
Explore the source record for details and available documents.
At the Royal Victoria Hospital in Montreal, 22 patients received two successive cadaver renal transplants. The results were analysed to determine which factors have the best predictive value for success or failure in renal retransplantation. The fate of a second cadaver renal allograft was found to be about the same as the first if the initial transplant has been lost because of rejection and not technical failure. The duration of survival of the initial transplant serves as the best guide to potential outcome of retransplantation after rejection of the initial graft.
In a consecutive series of 167 renal allotransplants, a statistically significant correlation was found between the number of pretransplant blood transfusions and the time of dialysis-dependent uremia. This correlation suggests that one possible explanation for the association of a beneficial effect of pretransplant blood transfusions with allograft survival may be in part due to the prolongation of uremia, which is a well-known immunosupressive factor. This begs the question of whether the transfusion-dialysis time association promotes a further selection factor leaving sensitized patients waiting for longer periods of time for transplants or unable to receive transplants at all. Whether the transfusion and the favorable prognosis association is also related to other specific immunological mechanisms remains to be proven.
In a single center, an unselected non-exclusion series of 78 consecutive cadaver renal allografts in 76 recipients was studied. Since 1971, using kidneys obtained from donors pretreated with large doses of cyclophosphamide and methylprednisolone, excellent clinical results with 2-year graft-survival of 70% 5-year graft survival of 66% have been obtained. The improvement in results is believed to be aided by the reduction in allograft immunogenicity due to short-term donor pretreatment. In this series, poor tissue-matching grades are notable, heavily transfused patients are few, 33 patients were high risk, and 43 patients were presensitized. In spite of these negative selection factors, the results obtained in this pretreated series, with 18% of graft losses due to rejection, are superior to those obtained in patients who did not receive pretreated allografts during the same time period, with 34% of graft losses due to rejection, and 2-year and 5-year graft survivals of 57% and 53%, respectively.
Cobra venom factor was used as a probe to evaluate the effect of depression of recipient hemolytic C3 activity on the sequential morphologic features of hyperacute cardiac allograft rejection in the rat. A series of ACI cardiac allografts transplanted to Lewis recipients presensitized &with ACI skin grafts was studied at arbitrary time periods over the initial 24 hours posttransplantation. The usual morphologic features of hyperacute rejection in this model, platelet aggregation, intravascular fibrin, endothelial destruction, neutrophil infiltration, and myocardial necrosis, were not observed in all allografts when recipient hemolytic C3 activity was virtually undetectable at the time of transplantation. Furthermore, allograft binding of rat C3 was not detected by immunofluorescence, although staining for IgG was commonly encountered. Despite profound depression of recipient hemolytic C3 activity, however, mononuclear cells were observed within the allograft microcirculation by 2 hours posttransplantation, and changes consistent with early cellular rejection were present in allografts examined at 24 hours. This study provides evidence that complement activation by graft-bound alloantibody is a critical effector mechanism of hyperacute rejection in this inbred rat model.
Explore the source record for details and available documents.
Utilizing a bone marrow cell immunization protocol designed to actively enhance renal or cardiac allografts, the in vitro mixed lymphocyte interaction has been studied. After immunization with allogeneic cells over a wide dose (10(5) to 10(8)) and time range, the mixed lymphocyte interaction using peripheral blood lymphocytes is reduced, and this reduction is shown in mixing experiments to be attributable to a circulating suppressor cell that has adherence characteristics of T lymphocytes. Specificity for in vivo generation of these circulating cells as well as specificity in the in vitro reaction was shown, although a nonspecific suppression background was observed. Allogeneic thymocytes, splenocytes, and platelets were effective in immunizing to generate these cells also. There was no general correlation with the ability to generate these cells and to actively enhance cardiac allografts, since suppression was seen after alloimmunization in strain combination that cannot be actively enhanced.
The relationship of F1 hybrid to parental strain cardiac allograft rejection rates to mixed lymphocyte reactivity in vitro has been studied in 10 strain combinations crossing the major histocompatibility barrier in three different models of acute rejection, accelerated or hyperacute rejection after skin graft immunization, and attempted active enhancement using 10(7) donor strain bone marrow cells. Although high and low reactivity could be discerned between the F1 hybrid and reciprocal parental strain in three of five instances in the one-way lymphocyte culturr reaction, low reactivity was only associated with prolonged graft survival in one combination. Two strain combinations giving high in vitro lymphocyte responses were associated with easily enhanced grafts. The BN strains was a low responder in vitro in the three combinations tested and as a recipient strain, allografts could not be actively enhanced. After skin graft presensitization, BN recipients rejected grafts hyperacutely in two of three combinations and with a median survival time of 2 days in the third combination. The association of poor in vitro proliferative responses, the inability to induce enhancement, and rapid graft rejection after skin graft presensitization could be related to genetic mechanisms controlling the amount and class or subclass of antibody or to the generation of suppressor cells and remains to be determined.
Explore the source record for details and available documents.
Graft hypoperfusion secondary to widespread vascular occlusion by recipient-derived platelet aggregates may be a major determinant of hyperacute cardiac allograft rejection in the rat. Since a hereditary platelet aggregation defect, attributed to decreased platelet levels of serotonin and adenine nucleotides and a depressed release reaction, has been described in the fawn-hooded rat strain, the effects of this intrinsic platelet function defect on the time course and morphologic features of hyperacute rejection have been evaluated. A series of nine heterotopic ACI cardiac allografts in fawn-hooded recipients actively immunized with ACI skin grafts were studied. Functional rejection with asystole was observed in all allografts from 8 to 40 minutes posttransplantation. Widespread platelet aggregation, endothelial cell destruction, interstitial widening, and focal myocardial alterations consistent with ischemic damage characterized all allograft. This study indicates that the platelet aggregation defect described for the fawn-hooded rat strain is one that does not alter the time course of the morphologic features of hyperacute cardiac allograft rejection, and thus this platelet aggregation abnormality has no essential role in the pathogenesis of this type of tissue damage.