Effect of blood transfusions on renal allograft survival.

One and two-year allograft survival rates of 117 first and 20 second consecutive cadaveric renal allografts are analyzed. The following observations were made: (1) Pretransplant blood transfusions may not improve rate of allograft survival per se. (2) Pretransplant blood transfusions may, however, reduce the number and the severity of rejection episodes in the early posttransplantation period. Thus, the allograft survival, especially in the nontransfused patients, may perhaps be influenced more by the effective manipulation of immunosuppressive therapy during rejection episodes. (3) The presence of lymphocytotoxins per se may not have any deleterious effect on the survival of second allografts.     

Prolongation of renal allograft survival in DLA tissue-typed beagles after third-party blood transfusions and immunosuppressive treatment.

Significant prolongation of survival of nonrelated DLA-mismatched renal allografts has been obtained in beagle recipients receiving three blood transfusions from nonrelated donors prior to kidney transplantation and immunosuppression after transplantation. Nontransfused DLA-identical or DLA 1 haplotype-different littermates of the transfused dogs were used as controls. Lymphocytotoxic antibodies were formed after the blood transfusions. A quantitative immune reactivity score correlated with graft survival. Low scores prior to transplantation were found in five transfused dogs that did not reject their allografts. High scores prior to transplantation were found in four animals rejecting their graft and in one dog that survived after an abortive rejection episode. The great similarities between the results obtained in this animal model and the observations made in human transplant patients indicate that this model can be utilized for a further analysis of the possibilities of blood transfusions in protecting subsequent renal allografts from immunological rejection.     

The effect of transfusions and donor pretreatment on canine renal allograft survival

Allograft survival is influenced by a complexity of known and unknown factors. The effect of several types of transfusion on renal allograft survival has been studied in mongrel dogs. Nontreated and drug-pretreated kidneys were transplanted. Preoperative and peroperative cell suspensions of unrelated dogs were transfused to graft recipients. All recipients received low-dose postoperative immunosuppression. One peroperative transfusion of 100 ml third-party blood enhanced graft survival of nontreated kidneys significantly. A transfusion of 100 ml blood 14 days before transplantation led to variable results, whereas a transfusion of cells obtained from a third party spleen, given 14 days before transplantation, did not prolong graft survival of nontreated kidneys at all. The administration of procarbazine hydrochloride and methylprednisolone to the donor before procuring the graft increased survival of canine renal allografts significantly. A combination of donor drug pretreatment and 100-ml peroperative third-party blood led to graft survival comparable to that obtained by either treatment. Pretreatment of the recipient with spleen cells 14 days before transplantation even abrogated the effect of donor drug pretreatment completely. These results show that preoperative transfusions cannot successfully be combined with donor drug pretreatment as commonly practiced in man. This is a possible explanation for the conflicting data on donor pretreatment in man. Furthermore this study gives evidence for the effectiveness of a peroperative blood transfusion on kidney graft survival.     

Effect of prior parental blood transfusions on the survival of renal allografts from a DLA-identical sibling.

Renal allografting was performed between DLA-identical beagle littermates without immunosuppressive treatment. One transfusion of 200 ml of parental blood donor to induce the formation of antibodies against non-DLA antigens that might enhance renal graft survival. Kidney graft survival times of transfused dogs were compared with the survival times of transfused dogs were compared with the survival times of transfused dogs were compared with the survival times of DLA-identical nontransfused littermates. Blood transfusions did not have a significant influence on the median graft survival time. Antibodies against the kidney donor lymphocytes were not demonstrated after blood transfusion. However, antibodies were induced in three of the six animals tested as shown by the reactivity of the sera of these animals against a lymphocyte panel. Antibodies occurred in animals with long-term as well as short-term surviving grafts.     

Effect of pretransplant blood transfusions and splenectomy on renal allograft survival in the Lewis rat

Both pretransplant blood transfusions and pretransplant splenectomy have been shown to improve renal allograft survival in humans and experimental animals. A study was undertaken using the Lewis rat to determine if any combination of pretransplant splenectomy and pretransplant blood transfusions exerted either a synergistic or deleterious effect on renal allograft survival. Pretransplant splenectomy and pretransplant blood transfusions used singly significantly prolonged renal allograft survival. Pretransplant splenectomy followed by 3 blood transfusions also significantly prolonged renal allograft survival. This finding implies that secondary sites of suppressor cell activity, for instance lymph nodes, can be stimulated by blood transfusion and produce prolonged allograft survival in the absence of the spleen. No combination of pretransplant blood transfusion and splenectomy was synergistic. In fact, the group that had pretransplant transfusions followed by splenectomy had allograft survival no different from the control group.     

Effect of pretransplant stored donor-specific blood transfusions on early renal allograft survival in one-haplotype living related transplants

The effect of pretransplant stored donor-specific blood transfusions (DSBTs) on early renal allograft survival in 37 consecutive one-haplotype living related donor (LRD) transplants (group B) was compared with a similar consecutive series of 38 one-haplotype LRD recipients (group A) who did not receive DSBTs. All transplant recipients in both groups were treated with identical immunosuppressive protocols using azathioprine and prednisone. Forty patients received pretransplant DSBTs and three of these patients (8%) developed cytotoxic antibodies to their prospective donors. Neither hyperacute rejection nor hepatitis occurred in group B patients following DSBTs. One group B patient experienced a technical graft loss on the 1st postoperative day and was excluded from the rejection data. Graft survival at 3 and 6 months was 100 and 90% in group B recipients and 68% in group A recipients. All 12 group A graft failures resulted from acute nonreversible rejection episodes occurring during the first 3 months post-transplant. The three group B graft failures occurring at 6 months were attributable to chronic vascular rejection. Chronic rejection of the renal allograft was histologically documented in six group A and five group B patients by 6 months post-transplant. The use of stored donor blood offered a simple and easily monitored method of administering pretransplant DSBTs that was convenient to the donor and recipient. The administration of DSBTs did not appear to be harmful to the recipient. In fact, the use of pretransplant stored DSBTs in one-haplotype LRD renal transplantation appeared to improve the prospects of early graft survival in our experience.     

The timing of pretransplant transfusions and renal allograft survival

Analysis of over 3000 cadaveric renal allograft recipients transplanted between June 1977 and June 1982 as part of the South-Eastern Organ Procurement Foundation Prospective Study was performed to determine the influence of timing of blood transfusions (BT) on patient and graft survival. Four mutually exclusive BT groups were identified for 2480 first-transplant and 655 regrafted patients studied: group 1 (n = 348, 29, respectively) received no BT; group 2 (n = 256, 29, respectively) received perioperative BT only (i.e., at the time of, or within 10 days of transplant); group 3 (n = 972, 287, respectively) received preoperative BT only (i.e., 10 or more days pretransplant); group 4 (n = 904, 310, respectively) received both preoperative and perioperative BT. For first graft recipients, actuarial graft survival for group 2 was significantly greater (P less than 0.035) than group 1 (49% vs. 41% at one year; 35% vs. 25% at 4 years), but to a lesser degree than groups 3 or 4, which were equivalent (58% at one year and 38% at 4 years). For regrafted patients, actuarial graft survival was again significantly greater (P less than 0.03) for group 2 patients, as compared with group 1 (59% vs. 29% at one year), and group 3 and 4 patients were not significantly different from each other (45% and 48% at one year, respectively) or from group 2. Interestingly, for regrafted patients who were presensitized at the time of transplant, those in group 4 (n = 94) had significantly better graft survival than group 3 (n = 111) at all time points examined (54% vs. 47% at one year, 46% vs. 22% at 3 years). In all comparisons, increases in graft survival were associated with decreased graft loss resulting from rejection, and no significant differences in patient survival were seen between any of these groups. These findings indicate that: (1) perioperative transfusions alone may have benefit in decreasing allograft rejection; (2) perioperative transfusions provide no apparent risk for patients who have already received pretransplant transfusions; and, (3) sensitized regrafted patients who receive pretransplant transfusions may gain an additional benefit from perioperative transfusions.     

Mixed lymphocyte culture responses. Lack of correlation with cadaveric renal allograft survival and blood transfusions

One-way and two-way mixed lymphocyte reactions (MLRs) between 65 cadaveric renal allograft recipients (R) and their specific-donor (D) and pooled third-party (P) cells were measured using a 5-day assay. There was no correlation between the results expressed as stimulation index, absolute counts, or the relative response and graft survival in transfused allograft recipients. Nontransfused recipients whose first graft failed had significantly higher responses to P, but not D, than those with successful grafts. The one-way MLRs to P of 61 cadaveric graft recipients and 52 potential recipients were measured. No correlation was found between the magnitude of the response and the number of transfusions, time since the last transfusion, or peak cytotoxic antibody production. Our results suggest that a standard 5-day MLR has little clinical value in predicting the results of cadaveric transplantation in HLA-A,B-mismatched recipient-donor pairs. We could not demonstrate any overall effect of transfusions on the MLR, suggesting that this may not be the mechanism by which transfusions exert their effect on graft survival.     

Effect of blood transfusions on survival of cadaver and living related renal transplants.

The effect of blood transfusion was analyzed in 194 first cadaver renal transplants and 86 living related renal transplants. The association of blood transfusion with HLA genotyping and poor risk recipients was analyzed. Exclusion of poor risk recipients improved graft survival among the transfused group of patients but not in the small subgroup of nontransfused recipients. No effect of blood transfusion was observed in the living related group. Improved graft survival was observed in both the haplotype-matched and nonhaplotype-matched transfused cadaver recipients. The haplotype-transfused recipients had grafts survival rates of 69 and 66% at 1 and 2 years, respectively. The greatest beneficial effect was seen in the double haplotype-transfused cadaver recipients with graft survival rates of 80 and 71% for the same period. The lack of beneficial effect of transfusion in the living related patients is felt to be a result of the fact that the maximum effect had already been achieved by a far superior donor-recipient histocompatibility than is able to be achieved in a large group of cadaver recipients.