Cadaveric Donor Renal Transplantation Research Articles

CLINICAL EVALUATION OF INDUCTION IMMUNOSUPPRESSION WITH A MURINE IgG2b MONOCLONAL ANTIBODY (BMA 031) DIRECTED TOWARD THE HUMAN α/β-T CELL RECEPTOR

Mouse mAbs directed against the alpha/beta-TCR were tested in clinical phase II and in triple-blind, randomized phase III studies. A clinical phase II trial administered 50 mg of murine anti-human alpha/beta-TCR mAb (BMA 031) intravenously on the day of, as well as 2 and 4 days after, cadaveric donor renal transplantation in combination with a CsA/prednisone regimen. None of 12 patients showed even moderately adverse side effects. A phase III, triple-blind randomized trial enrolled 24 patients in the BMA 031 group and 22 patients in a placebo control group. BMA 031 treatment significantly reduced the incidence of rejection events within the first 10 posttransplant days to 1 patient versus 9 episodes in the placebo group (P < 0.01). By the end of 30 days, 6 rejection episodes had occurred in the BMA 031 group and 11 in the control cohort (P = NS). After a minimum of 30 months follow-up, the actual allograft survival rate was 87% in the BMA-treated group compared with 68% in the control cohort.

THE CROSSMATCH IN RENAL TRANSPLANTATION

Flow cytometry (FC) is increasingly being used as a crossmatch procedure in addition to the standard complement-dependent cytotoxicity (CDC) test. In fact, FC offers a number of advantages over CDC and has the potential to become the primary crossmatch technique for cadaveric donor renal transplantation. We evaluated this possibility in 230 patients crossmatched by both CDC and FC. The results showed that when the T cell crossmatch was negative by FC it was always negative by CDC, and that when the T cell results were positive by CDC (IgM antibodies excluded) they were also positive by FC. As expected, a number of tests were T cell-positive by FC but negative by CDC. A T cell CDC crossmatch was more likely to be positive when FC was positive for both T and B cells and when FC results were quantitatively higher. However, FC was unable to consistently predict a positive, dithiothreitol-resistant B cell CDC crossmatch. A policy to transplant patients with negative FC results (70% of the patients evaluated) and not to transplant sensitized patients with FC+ T cell results (10%) would allow us to make a final decision with only FC in 80% of the cases. Actual graft survival was similar for nonsensitized first-transplant candidates with positive (83%) or all patients with negative (86%) FC results. We conclude that FC is sufficient to make a final decision in most cases. Wider utilization will require improvements in the ability of FC to measure B cell antibodies and to quantitate antibodies to T cells.

Outcome of renal transplantation in children less than two years of age

Outcome of renal transplantation in children less than two years of age. Twenty-two renal transplants were performed in 21 children less than two years of age at Children's Hospital. Fourteen were from living related donors and eight were from cadaveric donors. The five year patient and graft survivals of these recipients were compared to all other pediatric recipients between two and 18 years of age who received renal transplants over the same time period. Five year graft survival for recipients less than two years of age was 86% following living-related donor transplantation and 38% following cadaver donor transplantation. Older pediatric recipients aged between two and 18 years had a five year graft survival of 73% following living-related donor renal transplantation, which was similar to that for recipients less than two years of age. Although older cadaveric recipients had a comparable five year graft survival to younger recipients, at 42%, the patterns of graft loss were different. Graft failures in young recipients occurred within the first seven months post-transplant, whereas the older recipient's grafts failed more gradually. Actuarial five-year patient survival in recipients less than two years of age was 86% following living-related donor renal transplantation and 70% following cadaver-donor renal transplantation. Recipients less than two years of age had a poorer patient survival than older recipients following both living-related donor renal transplantation (P = 0.06) and cadaver-donor renal transplantation (P

THE LARGE CENTER VARIATION IN HALF-LIVES OF KIDNEY TRANSPLANTS 1,2,3

Based on a log-linear model for analyzing multiple effects, center variation in the UCLA Transplant Registry is the most influential factor in early renal graft survival. Among 68 active centers accounting for 70% of all transplants between 1985 and 1989, the 1-year graft survival (adjusted for 15 covariates) varied from 60 to 90%. The long-term graft survival, as measured by the half-lives of the first cadaver donor transplants at these centers, based on a minimum of 4 years of follow-up data, varied from 3 to 26 years. Although there was some correlation (r = 0.24) of half-life with the 1-year graft survival rate at each center, in many instances, excellent centers had poor half-lives and average centers had excellent half-lives. From a Cox regression analysis on data from 6752 first cadaver-donor renal transplants surviving beyond 1 year (submitted to the UNOS data base), white female recipients of 0 HLA-AB-mismatched kidneys not requiring dialysis in the first week posttransplant had projected half-lives of 14.1 years, whereas black male recipients of 4 HLA-AB-mismatched kidneys requiring therapeutic dialysis had half-lives of 2.3 years. However, adjustment for these factors could only remove 17% of the total variability in the centers' half-lives. Consequently, any algorithm intended to judge a center's renal transplant capabilities should include, even after adjustment for covariates, some function of both 1-year graft survival and half-life beyond 1 year.

ANALYSES OF THE UNOS SCIENTIFIC RENAL TRANSPLANT REGISTRY AT THREE YEARS—EARLY EVENTS AFFECTING TRANSPLANT SUCCESS1–3

The success of cadaveric renal transplants in the first year is determined largely by events that transpire during the transplant hospitalization. This conclusion is based upon analyses of data on 19,525 cadaver donor renal transplants performed since October 1987 and reported to the UNOS Scientific Renal Transplant Registry from more than 200 centers nationwide. Graft survival rates at 1 year differed by 20-30% depending upon whether or not the transplanted kidney functioned immediately and upon whether the patient required dialysis during the first week posttransplant, experienced rejection, or was discharged with a kidney that was functioning well. Recipients whose discharge serum creatinine level was less than 2.6 mg/dl or whose graft was functioning well at the time of discharge had 88% 1-year graft survival. A multistep logistic regression analysis showed cold ischemia time, transfusions, donor age and cause of death, HLA-DR mismatches, and peak sensitization to be significant factors in the first week. Prophylactic antilymphocyte antibodies (ALG/OKT3) reduced the incidence of rejection from 30% to 20% during the transplant hospitalization, but apparently only delayed rejection. By 6 months there was only a 3% reduction with ALG and a 5% reduction with OKT3 in the incidence of reported rejection and a 2% difference in 1-year graft survival. Although graft and patient survival are important measures of transplant success, graft survival is predicted upon both early and late events. The course of the transplant during the initial hospitalization and the quality of function at discharge were the strongest determinants of 1-year graft survival.

HLA‐D region restriction fragment length polymorphisms in living‐related and cadaver donor renal transplantation

DNA typing was used to examine the restriction fragment length polymorphism (RFLP) for the HLA‐D region and the T‐cell antigen‐receptor genes in donors and recipients of successful and rejected kidney transplants. The results in 15 HLA‐identical MLC‐non‐stimulatory sibling donor‐recipient combinations demonstrate that, in one instance, where the graft was removed due to rejection, the donor had two HLA‐D region gene RFLPs, (Bam HI‐DRB; Eco RV‐DQB), not present in the recipient. In contrast, polymorphism observed with these two restriction endonucleases was identical in two other HLA‐identical donor‐recipient combinations with rejected kidneys, as well as in all cases with functioning allografts. DNA typing was not helpful in distinguishing between 7 HLA‐haploidentical living‐related sibling and parent‐to‐child or 33 unmatched cadaver donor‐recipient pairs with and without functional transplants. When the TcR gene RFLPs were analyzed, all 12 recipients of HLA‐identical sibling allografts with successful transplants were identical or matched for the TcR β chain polymorphism. In contrast, all 3 recipients in this group who had rejected the kidney were mismatched or were not identical for the TcR β chain RFLPs. Extensive analysis of the TcR genes in the 7 haploidentical living‐related and 33 mismatched cadaver allograft donor‐recipient pairs failed to reveal any significant correlations between RFLP matching and clinical outcome. It is likely that DNA typing will be useful only in predicting or explaining rejection in some apparently HLA‐identical donor‐recipient pairs.

Renal transplantation of the infant and young child and the use of pediatric cadaver kidneys for transplantation in pediatric and adult recipients.

Transplantation of infants less than 1 year of age with kidneys from live-related parental donors has recently led to good results, whereas cadaver donor renal transplantation in this recipient age group has led to a high mortality rate (11/13). Similarly, the results of cadaver donor renal transplantation in infants and young children less than 5 years of age has been suboptimal in the past, although recent data are more encouraging. With recent availability of long-term peritoneal dialysis for the infant and young child with end-stage renal disease (ESRD), it is possible to defer transplantation until an optimal donor becomes available. Because of the possible immunologic hyperactivity of such recipients, the immunosuppressive regimen may need to be modified if improved cadaver donor survival rates are to be obtained. The use of anencephalic kidneys for transplantation has been associated with a high incidence of primary nonfunction and few recipients with long-term functioning grafts. Harvesting of kidneys from anencephalic donors declared "brain-dead" at birth may reduce the incidence of primary nonfunction and increase the availability of anencephalic kidneys for transplantation. Reports of the use of pediatric cadaver kidneys for transplantation into pediatric and adult recipients yields discrepant results. Analysis of the data indicates that if pediatric cadaver kidneys from donors less than 6 years of age are used, the potential for decreased graft survival rates and an increased incidence of technical complications exists. However, the use of pediatric cadaver kidneys can provide adequate graft function in both pediatric and adult recipients and the use of such kidneys should increase the number of kidneys available for transplantation.

Blood Transfusions and HLA Matching—An Either/or Situation in Cadaveric Renal Transplantation

Cyclosporine-treated recipients of primary cadaver donor renal transplants had a one-year graft survival rate of 79% if they received pretransplant blood transfusions (n = 5308). The one-year survival rate for nontransfused recipients (n = 709) was significantly lower at 69% (P less than 0.001). The transfusion effect was larger in black recipients (a 17% difference) than in white recipients (5%). The effect was also larger in recipients of grafts poorly matched for HLA-A, B, -B, DR, or -DR antigens than in recipients of well-matched grafts. Transfusions did not significantly improve graft survival in recipients with zero or one HLA-A, B or -B, DR, or zero -DR-mismatched grafts. However, transfusions accounted for increases of 10%, 14%, and 17% in patients receiving grafts mismatched at 2, 3, or 4 HLA-B, DR antigens, respectively. Several factors including cyclosporine and HLA matching have contributed to improving graft survival rates in nontransfused recipients. Sensitization was noted in 20% of transfused patients awaiting primary renal transplants in Southern California, as compared with 10% in transplanted patients, suggesting a tendency to transplant nonsensitized patients. Of the sensitized patients, 75% were female. Based on these data, we suggest that high survival of primary kidney allografts in the cyclosporine era can best be maintained by the continued use of pretransplant transfusions for the majority of recipients--or, alternatively, by HLA matching for patients who are at higher risk of becoming sensitized.

HLA-DR2, a marker for class I antigen sensitization.

After analysis of 423 hemodialysis patients in a transfusion program and 461 cadaver-donor renal transplants, we found that HLA-DR2 frequency was significantly higher in the responder (36%) than in the nonresponder patient group (19%), according to the percentage of PRA (panel reactive antibodies). Among DR2+ patients, the percentage of hypersensitized patients was twice that of DR2- patients. Graft survival curves in cadaver-donor renal transplants indicated a significantly lower survival when recipients were DR2+, even in recipient-donor pairs identical for class II antigens but mismatched for class I antigens. The prognostic probability of low response to transfusions by a stepwise logistic regression analysis showed the influence of sex and DR2 phenotype. By multivariant discriminant analysis, we found that the DR2 phenotype was one of the most influential transfusion sensitization risk factors. Our preliminary conclusion is that DR2 can be related to immune responsiveness to class I antigens.

BLOOD TRANSFUSIONS AND HLA MATCHING—AN EITHER/OR SITUATION IN CADAVERIC RENAL TRANSPLANTATION1 Pressented at the 6th Annual Meeting of the American Society of Transplant Physicians, May 1987, Chicago, IL

Cyclosporine-treated recipients of primary cadaver donor renal transplants had a one-year graft survival rate of 79% if they received pretransplant blood transfusions (n = 5308). The one-year survival rate for nontransfused recipients (n = 709) was significantly lower at 69% (P less than 0.001). The transfusion effect was larger in black recipients (a 17% difference) than in white recipients (5%). The effect was also larger in recipients of grafts poorly matched for HLA-A, B, -B, DR, or -DR antigens than in recipients of well-matched grafts. Transfusions did not significantly improve graft survival in recipients with zero or one HLA-A, B or -B, DR, or zero -DR-mismatched grafts. However, transfusions accounted for increases of 10%, 14%, and 17% in patients receiving grafts mismatched at 2, 3, or 4 HLA-B, DR antigens, respectively. Several factors including cyclosporine and HLA matching have contributed to improving graft survival rates in nontransfused recipients. Sensitization was noted in 20% of transfused patients awaiting primary renal transplants in Southern California, as compared with 10% in transplanted patients, suggesting a tendency to transplant nonsensitized patients. Of the sensitized patients, 75% were female. Based on these data, we suggest that high survival of primary kidney allografts in the cyclosporine era can best be maintained by the continued use of pretransplant transfusions for the majority of recipients--or, alternatively, by HLA matching for patients who are at higher risk of becoming sensitized.

The detrimental effects of delayed graft function in cadaver donor renal transplantation.

Data collected prospectively on over 3800 cadaveric renal transplants performed between June 1977 and July 1982 by the 41 member institutions of the South-Eastern Organ Procurement Foundation were analyzed to determine the influence of delayed graft function (DGF) on patient and graft outcome. Approximately 35% of first graft recipients and 47% of regrafted patients were found to have DGF, as determined by the necessity for dialysis at one week posttransplant. First-graft recipients with DGF tended to include more black recipients, patients with higher peak levels of panel reactive antibody (PRA), less use of antilymphocyte serum (ALS) posttransplant, slightly longer organ preservation times and the more frequent use of organs by ice alone. Multivariate (Cox) regression analysis considering DGF simultaneously with ten other potentially confounding variables showed a highly significant association between DGF and overall graft loss from all causes (P less than 10(-5], irreversible graft rejection (P less than 0.001) as well as patient death (P = 0.012). The differences in graft survival between first graft recipients with DGF (n = 961) versus those without DGF (n = 1769) at one and four years posttransplant were 46% +/- 2 vs. 60% +/- 1 and 28% +/- 3 vs. 40% +/- 2, respectively. The detrimental effect of DGF was highly significant irrespective of the source of donor organs or the type of preservation used. For first transplant recipients who recovered good graft function by one month following DGF (n = 564), there was a significant decrease in eventual graft survival, as compared with patients who had graft function at one month but no prior history of DGF (n = 1407; P = 0.008). However, patients with history of DGF who had good graft function at six months (n = 361) showed no significant difference in longer-term graft survival when compared with similar patients with good graft function at six months but no history of DGF (n = 912). Interestingly, first transplant recipients with DGF were found to have significantly better graft survival if they had received bilateral native nephrectomy at least one month prior to transplantation. These results indicate that delayed graft function following cadaver donor renal transplantation provides a significant risk for eventual graft and patients survival that is principally manifested during the first six months posttransplant. In addition, patients who recover graft function following DGF appear to also remain at higher risk for early graft loss, while pretransplant bilateral native nephrectomy may afford some protection against the detrimental effects of DGF.

Benefits of HLA-A and HLA-B matching on graft and patient outcome after cadaveric-donor renal transplantation.

Data collected prospectively on 3811 renal transplantations performed between June 1977 and July 1982 by the 42 member institutions of the South-Eastern Organ Procurement Foundation were analyzed to determine the influence of donor-recipient HLA-A and HLA-B matching on patient and graft outcome. Well-matched recipients were more likely to have received kidneys from outside their own centers, were more highly presensitized, included fewer blacks, and were more likely to have lost an earlier graft. Multivariate Cox regression analysis that included these and six other potential confounding variables revealed a significant association (P less than 0.001) between good HLA-A and B matching and increased graft survival. The difference in mean (+/- S.E.) actuarial graft survival between recipients worst matched and best matched for HLA-A and B antigens increased with time: 55 +/- 2 per cent as compared with 64 +/- 4 per cent at six months and 18 +/- 4 per cent as compared with 44 +/- 7 per cent at four years. Poor HLA matching of donor with recipient provided the greatest relative risk (2.16) of irreversible graft rejection of all the variables examined. Among patients with functioning grafts, well-matched recipients had lower serum creatinine levels and received significantly smaller amounts of glucocorticoids. Our findings indicate that good HLA-A and B matching is highly dependent on a system for sharing organs among institutions, and results in decreased graft rejection, better long-term graft function, and less need for post-transplantation immunosuppression.

THE INFLUENCE OF PRETRANSPLANT TRANSFUSIONS, USING DIFFERENT BLOOD PRODUCTS, ON PATIENT SENSITIZATION AND RENAL ALLOGRAFT SURVIVAL

An analysis of data collected during the South Eastern Organ Procurement Foundation (SEOPF) Prospective Study from 1977-1982 was performed to identify the relative effects of different blood products on patient sensitization and graft survival in cadaveric donor renal transplant recipients. More than 2700 primary and 800 regrafted patients from 40 transplant centers were included in this study. A significant increase in actuarial graft survival was seen in primary recipients who had pretransplant transfusions with only frozen blood (P less than 0.003), washed blood (P less than 0.0005), packed blood (P less than 0.0001), or any combination of blood products (P less than 0.002) as compared with those who received no transfusions. No blood product was found to provide a significantly greater increase in graft survival than any other blood product. Likewise, regrafted patients had significant and equivalent increases in graft survival associated with each type of blood product examined. The increased graft survival associated with each blood product was the result of decreased graft rejection, and not apparently related to other differences among patients receiving different types of blood. Furthermore, the type of blood used in pretransplant transfusions did not significantly influence the degree of patient sensitization for first-graft recipients, although regrafted recipients who received packed blood or a combination of blood products showed a slightly greater degree of sensitization than those who received only frozen or washed blood. First-graft recipients given packed or mixed blood had a small, statistically insignificant increase of hepatitis B virus (HBV) antigenemia, compared with those receiving frozen, washed, or no blood. Regrafted patients given any type of transfusion had a 3-4-fold increased incidence of HBV antigenemia as compared with nontransfused patients, but this difference also was statistically not significant. These findings suggest that the benefits of increased graft survival and the risks of sensitization or HBV infection associated with pretransplant transfusions are not significantly affected by the type of blood used.

The effect of cyclosporine on early graft function in human renal transplantation.

The effect of cyclosporine and steroids on early renal allograft function and eventual graft outcome was analyzed in 100 recipients; 33 recipients of living related donor (LRD) and 67 recipients of cadaveric donor (CAD) allografts were studied. A concurrent population of 47 CAD recipients treated with azathioprine and steroids was used for comparison. Recipients received oral cyclosporine (14 mg/kg) 48 hours (LRD) or 6-12 hours (CAD) pretransplant. No cases of acute tubular necrosis (ATN) were observed in the LRD recipients. The incidence of posttransplant ATN was similar in the cyclosporine-treated (41%) and in the azathioprine-treated (45%) CAD recipients (P = ns). Cyclosporine-treated CAD kidneys preserved less than 24 hr experienced a lower rate of ATN (P less than .01) using simple cold storage (31%), as compared with hypothermic pulsatile perfusion (57%). One-month creatinine nadirs were higher in cyclosporine-treated than in azathioprine-treated recipients, using median values for each group. One-year actuarial patient survival for cyclosporine-treated LRD recipients was 97%; CAD recipients, 94%, and azathioprine-treated CAD recipients, 91%. Graft survival rates in the same groups were 91%, 76%, and 55%, respectively. The major causes of graft loss in cyclosporine-treated patients were nonimmunologic. It is concluded that cyclosporine and prednisone are a safe, efficacious combination for LRD and CAD renal transplantation. The possibility of nephrotoxicity leading to impaired graft function in the early posttransplant period should not preclude the administration of cyclosporine prior to alloantigen presentation.

Long-term success with double pediatric cadaver donor renal transplants.

Many institutions are reluctant to use pediatric cadaver kidneys for transplantation because of a fear of an increased risk of technical complications or because these grafts leave the recipient with a relatively small amount of functioning renal tissue. From 1971 to 1981 the authors performed 21 double pediatric cadaver donor renal transplants. Eleven of these grafts are currently functioning for periods up to 11 years post-transplant. Only one graft was lost due to a technical complication. Using actuarial analysis, the graft survival and patient survival in this group of patients was compared with a control group of 39 computer matched and randomly selected recipients of adult cadaver kidneys and to all nonmatched recipients of cadaver kidneys during the same time period. There were no statistically significant differences among the three groups in graft survival or in patient survival. It is concluded that the long-term results with double pediatric cadaver kidney transplants are the same as those using single adult cadaver kidneys. Pediatric kidneys should be used whenever they are available so that transplantation can be extended to more patients.

Development of anti-HLA antibodies following renal transplantation--their characteristics and natural history.

Sera from 75 recipients of first cadaver donor renal transplants were analyzed for the development of anti‐HLA antibodies utilizing a complement dependent micro‐cytotoxicity assay. Anti‐HLA activity was assayed utilizing peripheral blood lymphocytes from a panel of normal donors. Anti‐HLA reactivity was felt to be present when a cell‐serum interaction yielded greater than 30% cell death. Reactivity was quantified as the percentage of donors reacting to a particular serum (PRL). Marked increase in PRL activity was demonstrated in 22 of 44 recipients rejecting their allografts and in some development of PRL reactivity could be demonstrated during immunosuppression and before allograft removal. In contrast, PRL reactivity was minimal in recipients with successful allograft (5 of 31 recipients) and this anti‐HLA activity was transient, disappearing after 6 months. Careful analysis of these anti‐HLA antibodies developing post‐transplantation, revealed that these antibodies to a large extent were very broadly reactive (multi‐specific) and could be absorbed out with platelets. Rather surprisingly, development of monospecific antibodies reactive to the mismatched HLA antigens, even early in the transplant course, was uncommon. These observations necessitate a re‐evaluation of “unacceptable” donor HLA antigens for second transplant recipients, especially since anti‐HLA alloantibody formation lacked “private” specificity and was present in only half the recipients rejecting their allograft. Additionally, these observations make one wonder whether “public” specificities on the HI.A molecule arc important in transplant compatibility.Since only half the recipients rejecting their allografts developed these broadly reactive alloantibodies, it became important to analyze factors that could predispose to alloantibody formation. Previous transfusions, pregnancies, number of rejections, degree of HLA antigen mismatch and presence of autolymphocytotoxins did not appear to have a major influence. However, recipients with HLA—A3 and a mismatch at the B locus appeared to have a decreased likelihood of developing these antibodies.

Superiority of B locus matching over other HLA matching in renal graft survival.

Graft survival after 348 consecutive first cadaver-donor renal transplants was significantly improved by HLA matching when recipients who had received pretransplant blood transfusions were matched with their kidney donor for two HLA-B locus antigens. No other type of HLA matching significantly improved graft survival in transfused recipients nor did any type of HLA matching in non-transfused recipients. Matching for one HLA-DR antigen had no benefit in transfused recipients. Only two patients received kidneys matched for both DR antigens and only two of those in whom DR matching had been performed had not been transfused. These results indicate that pretransplant blood transfusion and selection of graft recipients predominantly on the basis of HLA-B matching has significantly reduced the renal graft rejection rate in Newcastle upon Tyne over two years. Thus, HLA-B antigen matching should be adopted as the main criterion for kidney sharing between transplant centres.

Diagnostic and prognostic significance of an increase in fractional protein clearance ratio before and during rejection of renal transplant.

We measured prospectively changes in fractional protein clearance ratio (CPr/CCr) in 21 live-related (LR) and 41 cadaver donor (CD) renal transplants before and during onset of first rejections. Fifty-three recipients manifested a rejection within the first post-transplant month. Fractional protein clearance increased in all patients during rejection. An increase in CPr/CCr prior to other evidence of impending rejection, and therefore clinically useful, required at least a 10-day rejection-free interval dated from onset of diuresis (whether diuresis was immediate or delayed by acute tubular necrosis (ATN)). Twenty-three of 25 nonantilymphocyte globulin (ALG)-treated CD transplants manifested clinical and laboratory signs of the first rejection episode prior to the 10th day of diuresis compared with 5 of 21 LR and none of 16 ALG-treated CD transplants. Persistence of elevated CPr/CCr despite treatment forecast graft loss (11 of 13), whereas a decrease in this ratio was associated with ultimate reversal of the rejection process.

Cadaver donor renal transplantation by centers of the Southeastern Organ Procurement Foundation.

This report summarizes the results after two years of a continuing prospective study of cadaver donor renal transplantation being conducted by the Southeastern Organ Procurement Foundation (SEOPF). Data are presented on 942 first grafts. Blood transfusions were found to be a major (if not the major) determinant of allograft survival. HLA-A and -B matching was of significant value and the effect of compatibility became more significant as time passed. ALS provided for better long-term survival of more compatible grafts, but it was not a "safer" immunosuppressant. Autogenous nephrectomy appeared to aid in the survival of more incompatible allografts, but not more compatible allografts. Kidneys obtained and implanted locally and kidneys obtained at one center and implanted at another had the same incidence of acute tubular necrosis (ATN) as well as the same patient and graft survival. Preservation time did not relate to ATN, patient survival, or graft survival (within the limits of the study); however, ATN did adversely affect graft survival. The final systolic pressure of the perfusion pump was the only perfusion characteristic which predicted ATN. Race, sex, pregnancy, and duration of dialysis did not correlate with graft survival if the effects of transfusions and compatibility were controlled.

A COMPARISON OF FLUSHING FLUIDS FOR INITIAL PERFUSION OF KIDNEYS FOR TRANSPLANTATION

Four solutions for initial flushing of kidneys prior to transplantation were tested under conditions designed to resemble those of clinical cadaveric donor renal transplantation. The experimental model was the dog subjected to bilateral nephrectomy with renal autograft. Kidney grafts were subjected to 15 minutes' anoxia in vivo, 30 minutes' warm ischaemia at 37 degrees C ex vivo, and two hours' cold ischaemia before reimplantation. The four solutions used were Collins (C3), Perfudex (P), hyperosmolar citrate (HC), and a solution of bovine albumin containing dog red blood cells (BBA). Effects of the flushing fluids were compared by parameters relating to dog survival, renal function, and serum enzyme levels. With all parameters studied the best results occurred in HC perfused kidneys. Results with BBA perfusion were marginally worse, while C3 perfused kidneys were again inferior. P perfused kidneys clearly did least well. The results support the use of HC for clinical application.