Showing papers in "Clinical Transplantation in 1987"

The transfusion effect.

Abstract: 1. Pretransplant blood transfusions improved the survival of first cadaver donor renal allografts by 10% at one year in CsA-treated recipients. 2. Pretransplant transfusions improved the survival of living-related donor transplants as well. HLA-identical sibling grafts had a 5% higher graft survival rate in transfused than nontransfused patients. Living-related donor transplants in one haplotype-mismatched combinations had a 10% higher one-year graft survival rate in transfused recipients. One-year graft survival in nontransfused recipients of one haplotype-mismatched sibling transplants was 75%, a result slightly lower than that for CsA-treated first cadaver donor recipients. 3. Transfusions given prior to retransplantation did not improve survival of the second graft. As patients who have previously rejected a transplant are at high risk of sensitization, blood transfusions should be avoided if possible. 4. For black recipients, transfusions improved one-year cadaver graft outcome by 17%. The effect was smaller in white recipients (8%), but significant nevertheless. One-year graft survival was 55% in nontransfused blacks and 68% in nontransfused whites. The impact of recipient race on the transfusion effect may explain some of the discrepancies between the UCLA and European registries on the magnitude of the transfusion effect. 5. Even centers with high overall success rates with cadaver donor transplants had poor graft survival in nontransfused recipients. The transfusion effect cannot be explained simply as a reflection of center performance. 6. The number of transfusions required to see an improvement in graft survival was small. Even a single transfusion significantly improved graft outcome in male and nulliparous female recipients. Since the risk of sensitization increased with multiple transfusions, large numbers of unnecessary transfusions should be avoided. 7. There may be alternatives to transfusion for those patients unwilling or unable to accept blood products and for patients at high risk of sensitization (parous females) as a result of transfusion. HLA matching resulted in high survival rates among nontransfused recipients.

Liver transplantation: the recent Cambridge-King's College Hospital experience.

Abstract: This authoritative text compiles expert contributions from recognized leaders in the field. Topics covered include experiments with animals, candidates for the liver graft, the operation, post-operative care, pathology, results and conclusions.

The flow cytometry crossmatch in kidney transplantation.

Abstract: 1. Positive FCXM reactions were associated with sensitization in transplants with negative cytotoxic crossmatches. Recipients of regrafts, females, particularly those with previous pregnancies, and recipients with historical cytotoxic antibody reactivity were more likely to have FCXM detectable antibodies. 2. Primary nonfunction grafts were associated with a positive FCXM, but predominantly in those transplants involving female, older, or nontrauma donors. Nearly 40% of the FCXM positive transplants of these organs did not function during the first month posttransplant 3. Low 3-month graft survival rates were associated with a positive FCXM reaction, but once again this was seen with female, older, and nontrauma donor transplants. In addition, approximately 40% of FCXM positive transplants involving older or nontrauma donors that did survive had poor graft function at 3 months.

Long-term survival of kidney allografts.

Abstract: 1. Late graft loss rates did not improve substantially in patients with functioning grafts one or 5 years posttransplant when compared with all patients in pre-CsA kidney transplants. Graft loss rates were the same for recipients of first and regraft transplants involving cadaver donors after the first year posttransplant. 2. Long-term graft survival rates have not improved over the years to any great degree, in contrast to one-year rates. 3. The long-term patient survival rates have improved dramatically over the years for both cadaver and living donor transplants. 4. In recent transplants, zero HLA-A,B mismatched grafts appear to have an advantage in terms of long-term graft survival both with and without CsA immunosuppression. Matching for HLA-DR alone did not influence long-term graft survival rates. 5. In cadaver donor grafts, those with zero mismatches for HLA-B,DR or HLA-A,B,DR antigens had the highest long-term graft survival rates, particularly with transplants involving CsA. 6. From these long-term projections, it would seem that histocompatibility continues to exert a major influence on transplants in the CsA era. Only living-related donor or well-matched cadaver donor transplants appear likely to have high long-term graft survival rates.

Influence of race on renal allograft survival in the pre- and postcyclosporine era.

Abstract: In conclusion we find that white cadaveric recipients of renal allografts have clearly benefited from the use of CsA. Matching for the major histocompatibility antigens, especially HLA-B + DR, is also associated with improved allograft survival in whites. For black cadaveric recipients there was no significant improvement in allograft survival with the use of CsA nor with matching for HLA. In contrast, for recipients of LRD kidneys both races appear to benefit from the use of CsA over conventional therapy. Consequently, it is clear that with the excellent allograft survival in LRD black recipients that matching can have a significant beneficial effect. However, the differences in survival between the races of cadaveric recipients suggest that for blacks the use of CsA cannot overcome the inherent genetic or physiologic differences that may exist. These results suggest that blacks should be targeted for concentrated study, the benefits of which would be to increase our understanding of potential factors influencing allograft survival in a group that comprises an increasingly larger proportion of candidates on waiting lists throughout the United States. 1. Overall renal allograft survival in CsA-treated black recipients is significantly lower than in comparable white recipients. The major period of allograft loss is in the first 6 months after which the rates of allograft loss for blacks and whites are similar. 2. There was a 12% increase in allograft survival in CsA-treated cadaveric recipients compared to pre-CsA-treated recipients. Allograft survival in white recipients has increased 15% whereas for black recipients there was only a 5% improvement over the azathioprine-prednisone treatment group. 3. Overall, there was a significantly improved graft survival for primary transplants compared to retransplants. Renal allograft survival in black CsA-treated recipients of primary transplants was significantly lower than in comparable whites, whereas there was no significant difference in graft survival between black and white recipients of retransplants. 4. Allograft survival rates in black and white recipients of kidneys from living-related donors were not significantly different from each other in either the non-CsA or the CsA immunotherapy group. 5. Overall there was improved allograft survival with increased matching for HLA-DR or B + DR compared to a zero match in CsA-treated recipients. Significantly, the effect of matching for HLA-DR or B + DR was seen only in white recipients.(ABSTRACT TRUNCATED AT 400 WORDS)

Original disease of the recipient.

Abstract: 1. The influence that a patient's original disease had on the outcome of kidney transplantation was small when recent transplants (1983 to present) were examined. A difference of only 5% was seen in one-year graft survivals of first cadaver donors. The average one-year survival was 70%; patients with pylonephritis having the best (75%) and SLE patients the worst (65%) survival rates among the major disease categories. 2. There was little difference observed in patient survivals or functional graft survivals in first cadaver transplants among patients with different original diseases. This was also the case with cadaver regrafts; with the exception of polycystic kidney patients who had quite poor graft survival (41% at one year) with regrafts. Pretransplant blood transfusions resulted in increased cadaver graft survival; however the low number of nontransfused patients in many disease categories presented difficulties in examining this effect. 3. The use of cyclosporine resulted in increased cadaver graft survival in all disease categories. One-year cadaver graft survival of cyclosporine-treated patients averaged 75% compared to 63% with noncyclosporine-treated patients. A beneficial effect of cyclosporine use was not consistently seen in transplants involving living-related donors, although perhaps larger numbers of patients are required in order to confirm this observation. 4. Graft survival in diabetic patients was quite good in this analysis of recent transplants. First cadaver one-year graft survival in diabetics was only 4% below the overall average and 2% less with cyclosporine. Patients with both juvenile (75% one-year graft survival) and adult-onset (78% one-year graft survival) forms of the disease had good graft survival when cyclosporine was used for immunosuppression.

The center effect.

Abstract: 1. Transplant centers were grouped according to one-year graft survival rates of first cadaver transplant recipients treated with CsA. Not surprisingly, the major differences among center groups were associated with the success achieved with CsA in both patient and graft survival. Centers with the poorest survival rates were those with the least improvement over azathioprine and prednisone immunosuppression. 2. There was a definite "learning curve" associated with improvements using CsA immunosuppression for excellent and good centers. Fair centers have yet to see a significant improvement in graft survival overall with CsA. 3. Survival rates for living-related transplants varied little among the center groups, suggesting that most centers do equally well with low-risk transplants. 4. Pretransplant risk factors such as HLA matching, sensitization status, age, sex, and race of the recipients, and ischemia times varied little among the center groups. The center effect cannot be explained by recipient demographic risk factors.

Current problems in cardiac transplantation.

Abstract: In conclusion, after almost 20 years of clinical application and due to much progress during that time by the pioneers of the method, cardiac transplantation is now a safe and reliable treatment for patients in intractable cardiac failure untreatable by other medical or surgical means. Several challenging problems remain to be resolved by the many active and excellent centers now engaged in this promising field.

Sensitization after transplantation.

Abstract: 1. Out of 122 sera from patients who had rejected a kidney transplant, 82% had cytotoxic antibodies to HLA. These antibodies were present in about equal frequency regardless of when the graft was rejected. Twelve patients who had rejected their grafts after 5-15 years also produced clear HLA antibodies. 2. The HLA antibodies were not directed to all the mismatches of the donor, but rather appeared to be against a few of the specificities. Thus the graft could have been rejected by a response directed at a few major determinants. Antibodies to some antigens were not detected at all. 3. Some patients produced their HLA antibodies many months after the rejection of their first graft.

Kidney Transplantation in Pittsburgh: Experience and Innovations

Abstract: 1. The introduction of combined CsA and steroid treatment as the baseline immunosuppressive medication significantly enhanced the results of kidney transplantation in our series. But various other preexisting recipient or donor conditions may still have an important effect on kidney transplant survival and should not go unrecognized. 2. Living-related kidney transplants were almost totally abandoned at our institution. Reasons for this approach are the increased availability of cadaveric donor organs, the improved results with cadaveric transplants under CsA and the possible risks to the living donors. 3. Combined liver/kidney transplants have been shown to offer a favorable treatment modality for patients with endstage liver and renal failure. 4. A newly developed center-oriented Transplant Information Management System (TIMY) significantly facilitates the clinical and research tasks in our department. 5. An integrated, computerized scoring system for equitable allocation of donor organs has proven to be highly effective during routine clinical use.

Racial effect on kidney transplants.

Abstract: A Donor race effect 1. In 15 consecutive years from 1971 to 1986, grafts from white donors had a higher graft survival rate than from black donors. 2. The one-year graft survival rate of transplants from white donors was 76.1% compared with 65.6% from black donors (p less than 0.0001) in the period of 1984 to 1987. 3. When analyzed in 3 periods of 1971 to 1980, 1981 to 1983, and 1984 to the present, the higher graft survival rate for white donors compared with black donors was highly significant (p less than 0.0007) in all 3 periods. 4. This difference in survival rates from white and black donors disappeared completely when corrected for center category. Within each category of excellent, good, and fair centers, the survival rate was the same for grafts from white and black donors. The proportion of black-to-white donors was low at the excellent centers and high at the fair centers. 5. We therefore conclude that the donor race effect had been produced by more black donors being utilized at the poorer centers. Once this was corrected, no donor race effect was seen. B. Recipient race effect. 1. In 15 consecutive years from 1971 to 1986, white recipients had a higher graft survival than black recipients. 2. In the period of 1984 to the present, the one-year graft survival was 76.4% for white recipients compared with 69.3% in black recipients (p less than 0.0001). 3. In all 3 periods as given above for the donor race effect, white recipients had a superior survival rate which was highly significant (p less than 0.0001). 4. White recipients had a higher survival rate within all 3 categories of transplant centers. At the fair centers, the one-year graft survival was 72.8% for white recipients and 57.3% for black recipients (p = 0.0004). 5. The overall one-year graft survival of white recipients was 80.5% as compared with 69.5% for black recipients, an 11% difference. Since a higher proportion of black recipients is transplanted at the poorer centers, the corrected one-year graft survival is 74.1%. Thus, the difference of 6.4% is attributed to the recipient race effect and the remaining 4.6% to the center effect. 6. When the 3 categories of centers were examined for various factors, it was noted that black and white recipients had similar cold and warm ischemia times and donor age kidneys and were similar in recipient age.(ABSTRACT TRUNCATED AT 400 WORDS)

Pancreas transplant protocols at the University of Minnesota: recipient and donor selection, operative and postoperative management, and outcome.

Abstract: In summary, at the University of Minnesota we perform pancreas transplants from both living-related and cadaver donors. Living-related donors must meet strict criteria indicating that they are not at risk for diabetes. Segmental grafts are procured from living-related donors. We currently procure whole pancreas grafts from most cadaver donors, including those in whom a liver is procured. We will accept preservation times up to 24 hours using hyperosmolar silica-gel-filtered plasma as the preservation solution. In regard to recipient selection, we have several categories of patients, including nonuremic individuals with early secondary lesions of diabetes affecting the eyes, nerves, and kidneys. Pancreas transplants are also performed in patients with end-stage diabetic nephropathy, either simultaneous with or after a kidney transplant. The potential benefit from pancreas transplantation is greatest in patients who have early diabetic complications which in the absence of this intervention would progress to a severity more serious than the possible side effects of chronic immunosuppression. A careful pretransplant evaluation is necessary in order to select nonuremic, nonkidney recipients in whom pancreas transplantation is appropriate. The selection process is much easier in kidney transplant recipients; virtually any person who can withstand the additional surgery is a candidate, the risks associated with immunosuppression having already been accepted in lieu of the unsatisfactory alternative of chronic dialysis. The results we have obtained in the 3 categories of recipients since November 1984 in patients managed by our currently preferred surgical techniques and immunosuppressive protocols are shown in Figure 6. One-year pancreas survival rates in nonuremic, nonkidney transplant recipients are 63%, in recipients of a previous kidney 46%, and in recipients of simultaneous kidneys 75%. With respect to surgical technique, our current preference is the bladder drainage method because the ability to monitor exocrine function leads to earlier diagnosis and treatment of rejection episodes. With related donor transplant, we have continued to use enteric drainage. Because the rejection rate is much lower than with cadaver donors, the one-year functional survival rate has been relatively high for technically successful enteric-drained related donor grafts. Nevertheless, rejection does occur, and related donor segmental grafts are being performed with bladder drainage. Our current immunosuppressive protocol of quadruple drug therapy has been associated with the highest graft survival rates, particularly in the bladder-drained group where early diagnosis and treatment of rejection has been facilitated. In our experience, UAA monitoring results have had a high correlation with rejection episodes, and we have never seen loss of endocrine function with retention of high UAA levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Kidney transplantation and donor-recipient ages

Abstract: 1. With CsA treatment there has been an increase in procurement of older kidneys and transplantation of older recipients. 2. Recipient age shows a 5% difference in graft survival between the best and the worst. In contrast, donor age shows a 16% difference in graft survival. 3. Female donor kidneys have a poor prognosis that is not completely associated with early function. This may indicate increasing dysfunction between one month and one year. 4. The drop in serum creatinine levels is directly proportional to recipient age. In zero- to 10-year-old recipients the rapid serum creatinine drop may be due to the transplantation of a normal size kidney into a small recipient. 5. Matching is strongly indicated for recipients receiving kidneys from young or old donors. 6. Transfusion is indicated for all groups and particularly for young donors and recipients. 7. Ten-year functional graft survival indicates decreasing immunocompetence with increasing recipient age. Ten-year graft survival with different aged donors indicates high risk with young and old donors.

A single center experience with cyclosporine in renal transplantation: Ohio State University 1983 to 1987.

Abstract: 1. Equivalent graft survival for both diabetic and nondiabetic recipients can be accomplished in haploidentical living-related donor transplants with either DST and posttransplant conventional immunosuppression or a CsA-prednisone protocol without pretransplant DST. 2. There is an 8% difference in one-year graft survival between living-related (91%) and first cadaveric (83%) donor renal transplants. At 2 years this difference is 12%. 3. In primary cadaveric donor transplants, only diabetic status and immediate graft nonfunction (ATN) proved significant determinants of graft survival. The degree of HLA-A, B, or DR match, transfusion, recipient age, or level of presensitization, were all variables that did not significantly correlate with outcome. 4. In the retransplanted population the level of presensitization and the presence of immediate graft nonfunction (ATN) proved significant variables on univariant analysis. The relationship between recipient presensitization as reflected in PRA and the incidence of ATN and the interplay of these 2 variables on graft survival strongly suggest an immunologically unique environment in the recipient undergoing retransplantation that negatively impacts on graft survival and that is not present following presensitization of primary cadaveric recipients.

The Denver-Pittsburgh liver transplant series.

Abstract: Liver transplantation is now the preferred treatment for many diseases leading to end-stage liver disease. Transplantation for cancer has been disappointing and there is a significant recurrence rate after transplantation in hepatitis B-virus carriers. Additional strategies will have to be developed if we are to improve the results of transplantation for these patients. The role of immunological factors in liver transplantation continues to reveal significant differences from their role in renal transplantation and will continue to be an interesting area of study for years to come.

Heart transplantation--Stanford experience.

Abstract: Heart transplantation has evolved from an experimental procedure with minimally acceptable results to a therapeutic option for patients with end-stage heart disease. Since 1968, 429 patients have undergone cardiac transplantation at Stanford. The recipient diagnosis was cardiomyopathy in 205 patients, coronary artery disease in 188, and valvular heart disease in 20 patients. The age range was 5 months to 60 years with equal survival among children and adults. Immunosuppression included a 3-drug protocol of CsA, azathioprine, and prednisone. The current one- and 5-year survival is 83% and 55%, respectively. A totally implantable electrically driven left ventricular assist device (Novacor) has been implanted in 6 patients as a "bridge-to-transplantation." Four patients received cardiac transplants after a mean support period of 7 days (range 2.0-16.5 days). Of the four transplanted patients, 3 (75%) are alive at 32, 11, and 4 months. With improved immunosuppression and standardized protocols, heart transplantation has been successfully employed by many centers. The number of heart transplants has risen from 103 in 1982 to 719 in 1985. Undoubtedly, due to the expanding number of centers, future issues will include distribution of donors and minimal acceptable standards for heart transplantation centers.

Renal transplantation at the University of Minnesota during the 1980s.

Abstract: 1. There have been 1,225 renal allografts performed at the University of Minnesota between January 1, 1980 and May 31, 1987. Significant risk factors for graft survival include donor type, retransplantation, and age at time of transplant. In addition, diabetes is a significant risk factor in patient survival. 2. Three immunosuppressive regimens have been used during this time period: AZA + P + ALG, CsA + P, and CsA + AZA + P (+ ALG for CAD grafts). The 3 protocols have been received by 411, 205, and 356 primary renal allograft recipients, respectively. No overall differences between the therapies exist with respect to graft or patient survival. However, females, recipients of CAD organs (especially the recipient with diabetes), and patients 18-50 years of age at transplant have improved graft survival results using CsA + AZA + P (+ ALG). Females and the 18-50-year-old recipients also have improved results with respect to patient survival. 3. The 3 protocols [AZA + P + ALG; CsA + P; and CsA + AZA + P + ALG] have been used for 125, 112, and 174 primary recipients of CAD organs, respectively. Recipients of CsA + AZA + P + ALG have significantly better graft survival overall in the diabetic and poorly matched subgroups. Other high-risk (but small sample size) subgroups show statistically nonsignificant, but clinically important, improvements. These groups include patients over 50 years of age, patients with preformed antibodies, as well as those with compatible ABO blood types. Similar trends exist with respect to patient survival. 4. Risk factor analysis of all patients receiving CsA + AZA + P (+ ALG) indicates that donor type, retransplantation, and age at the time of transplant are still serious risk factors for graft survival. Only age at transplant influences patient survival significantly. 5. The failure to find any significant risk factors in primary recipients of CAD organs in the CsA + AZA + P(+ ALG) era, combined with the generally consistent good graft and patient survival rates, suggest that the traditionally high-risk patient can be successfully transplanted with excellent results. 6. Pediatric patients can be successfully transplanted with results equivalent to 18-50-year-old patients and better than those recipients over 50 years of age at the time of transplant. Random transfusions and combination therapy are at least as good as DST and AZA + P + ALG.

HLA matching effects.

Abstract: 1. Transplants without A,B mismatches that had good early function (grade A at 3 months) had a strikingly lower long-term failure rate (equivalently, longer half-life) than transplants that had poor early function. This was found in HLA-identical sibling donor transplants as well as in cadaver donor grafts. The same superiority was observed in parent donor grafts although the number of zero mismatch grafts in this group was too small to permit a sensitive analysis. In cadaver donor grafts, zero A,B mismatch transplants had a longer half-life than mismatched grafts in both early function groups in first transplants but only in the poorer early function group in regrafts. These results were based on transplants done from 1970 to 1979; there was not enough experience with DR-typed grafts for their inclusion into a similar analysis. This finding does not at present have consequences for recipient selection. The finding would have consequences if an association of early function with matching at another system (e.g., Lewis) or with some assessable non-responsiveness were to be shown. 2. The Excess Match Index (EMI), defined as number of matches less number of mismatches, was shown to be associated with graft survival. It was shown that within groups defined by number of mismatches, survival tended to be greater if the number of matches were more; likewise, within groups defined by number of matches, survival tended to be greater if the number of mismatches was less. The within-match group and within-mismatch group comparisons were based on small numbers of transplants and the corresponding findings are not firmly established. The potential significance of the index, which follows from the finer gradation of the extent of matching, is that it may supply a useful basis for priority schemes for selection of recipients, particularly in donor sharing programs. 3. A recipient selection scheme based on the EMI applied to DR matching was evaluated in a simulation study with the result that most of the gains from DR matching could be obtained with relatively small recipient pools. Nearly all of the gain was achieved by a pool size of 400 (pool size for ABO-identical recipients) and most of the gain could be achieved with smaller pools. The result is encouraging since it indicates that much of the gain from HLA matching can probably be achieved with practically attainable size recipient pools. It was important that the priority scheme not lead to a distribution of phenotypes in the pool that differs substantially from the population.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term results of cyclosporine-steroid therapy in 131 non-matched cadaveric renal transplants

Abstract: One-hundred-and-twenty-eight recipients of 131 consecutive, non-matched cadaver renal allografts were treated with cyclosporine and steroids. They have been followed for 4 to 6 yr. Cumulative patient survival at 1-yr was 92.2% and at 6yr it is 77.8%. Cumulative graft survival at 1-yr was 79.4% and at 6 yr it is 50.0%. After the high-risk 1st yr, the rate of graft loss was even and similar to that reported after the 1st yr for grafts treated with azathioprine and steroids. This indicates that cyclosporine nephrotoxicity has not had an obvious adverse effect on the survival of chronically functioning grafts. The results were better with primary grafting versus retransplantation, but were not significantly influenced by age, diabetes mellitus, or a delayed switch in patients from cyclosporine to azathioprine. We have concluded that cyclosporine-steroid therapy is safe and effective for long-term use after cadaveric renal transplantation.

Heart and heart-lung transplantation Papworth Hospital 1979 to 1987.

Abstract: The quality of life for those who survive the first 3 months after transplantation is generally good (10). The duration of hospital stay and the cost of transplantation per patient has been reduced during the last 3 years. Cardiologists are coming to appreciate the therapeutic potential of both heart and heart-lung transplantation. One of the chief logistical problems now being faced is that of increasing the provision of transplant services to match the increasing demand. It was said in an earlier edition of this book that this would be donor organ limited and that pattern already seen in the United States is becoming apparent in the United Kingdom. The broad principles of management of heart and heart-lung recipients have been established. Further improvements in medium and long-term results can be anticipated as a result of refining immunosuppression and defining the cause of chronic donor organ related damage (small vessel coronary occlusive disease in heart transplants and chronic obliterative bronchiolitis in heart-lung transplants). Heart transplantation has become firmly established as a therapeutic option for life threatening heart disease. It is probably too early to attribute this label to heart-lung transplantation which continues through its developmental phase with acceptable short-term results. Improvements in chronic damage characteristic of long-term survival in both heart and heart-lung transplant recipients will be a significant clinical step forward in this field.