Showing papers in "Clinical Transplantation in 1993"

Relief of hepatic vein stenosis by balloon angioplasty after living-related donor liver transplantation.

Abstract: We have experienced 5 hepatic vein stenoses in 3 children (8 to 23 months old) after living-related liver transplantation (total 48 liver transplants for 48 children between June 1990 and November 1992). The initial symptoms of hepatic vein stenosis were ascites and/or edema. The blood flow of hepatic vessels was monitored by duplex sonography. The mean velocity of the hepatic vein and the portal vein was decreased and flow wave pattern of the stenotic hepatic vein was flat. The patients were treated by percutaneous transhepatic balloon angioplasty. After a successful angioplasty, the mean velocity of the hepatic vein and portal vein increased and pulsatile waves returned to the hepatic vein. Arterial ketone body ratio (acetoacetate/3-hydroxybutylate) increased, promptly followed by recovery of other liver function tests. In 1 patient, this complication occurred three times with intervals of 7 months and 3 months between episodes of hepatic vein stenosis. In conclusion, hepatic vein flow should be monitored routinely with duplex sonography after living-related donor liver transplantation. Percutaneous transhepatic balloon angioplasty is a primary treatment for the stenosis.

HLA matching: identification of permissible HLA mismatches.

Abstract: Previous studies of mismatches for a single HLA antigen in kidney transplants have not demonstrated that any single HLA antigen was more immunogenic than another. Here we show that certain mismatched antigens are "permissible" to recipients of certain types and not to others. In this retrospective study of 1,273 living-donor kidney transplants, a mismatch for 27 different, single A,B,DR antigens was evaluated with respect to recipients of various types. Various combinations of donor/recipient incompatibilities were then classified as "permissible" or immunogenic, depending upon the fate of the transplant. This list was then evaluated with 1,905 patients who received cadaver-donor transplants mismatched for a single A,B,DR antigen. Cadaver-donor kidney transplants judged to have received a permissible mismatch in the A, B, or DR loci had graft survival rates equivalent to zero-A,B,DR-mismatched grafts. Among 425 patients with one-A,B,DR-permissible mismatches, one-year graft survival was 89% with a 14.1-year half-life, compared with 966 one-A,B,DR-mismatched grafts with an 89% one-year survival and an 18-year half-life. Based upon these results, we recommend the initiation of one permissible A,B,DR-mismatched transplants for national sharing. This will result in potentially 60% of shared transplants having high long-term graft survival rates.

Development of an index to predict posttransplant diabetes mellitus.

Abstract: The objectives of this study were to (1) identify risk factors and develop a prediction index for posttransplant diabetes mellitus (PTDM), (2) validate the risk factors and assess the index's predictive ability, and (3) modify the index to enhance its predictive accuracy. Preoperative variables included gender, race, age at transplantation, donor source, number of previous transplants, percentage of ideal body weight, family history of diabetes, and HLA type. Postoperative variables were glucose intolerance on postoperative days 0-3 and 4-7. Age, family history, glucose intolerance during postoperative d 4-7, and specific HLA types were significant independent risk factors for PTDM. No independent effects of race, gender, or donor source were detected. The four independent risk factors produced an equation that accurately predicted PTDM in 77% of the patients. Specificity and negative predictive values reached 75% and 97%, respectively, for the population of men.

Pancreas transplant results in United Network for Organ Sharing (UNOS) United States of America (USA) Registry with a comparison to non-USA data in the International Registry.

Abstract: As of 1994, more than 6,300 pancreas transplants were reported to the IPTR. More than 4,300 were performed in the USA, including more than 3,000 since the inception of the UNOS Registry in October 1987. The BD technique was used for 96% of USA cases but only for 64% of non-USA cases. In the overall analysis of USA BD cadaveric pancreas transplants reported to the registry by August 1994 (n = 3,000), patient survival and pancreas graft function survival rates were 91% and 72% at one year, 87% and 67% at 2 years, and 84% and 62% at 3 years, respectively. When the USA data for BD cases were analyzed according to the 3 major recipient categories: SPK, (n = 2584); PAK (n = 241); and PTA (n = 175)], patient survival rates were no different (91%, 91%, and 90% at one year, respectively), but pancreas graft survival rates were significantly higher in the SPK than in the PAK and PTA categories (76%, 47%, and 48%, at one year, respectively). In the SPK group, kidney graft survival rate at one year was 85%. Although the overall results were not as good for non-USA as for USA pancreas transplants, this was probably because the results with non-BD techniques were not as good as when BD was used, and in Europe, more than one-third of the cases were by techniques other than BD. The patient, pancreas, and kidney graft survival rates at one year for BD SPK transplants in Europe (n = 579) and other non-USA locations (n = 66) were similar to those in the USA; in Europe they were 92%, 78% and 84%, respectively. The graft survival rates for solitary pancreas transplants, however, were higher in the USA. Outcomes were also compared according to whether induction immunotherapy in USA recipients included ALG/ATG, OKT3, or neither. In the SPK category, there was no difference among the protocols, with one-year graft survival rates being 76% in the ALG/ATG (n = 1,130), 78% in the OKT3, (n = 927) but 69% in the Neither (n = 294) group (which had a significantly lower graft survival). In the PAK category, the use of OKT3 (n = 49) was associated with lower graft survival rates than when ALG/ATG (n = 154) or neither (n = 37) were given (33%, 51%, and 48% at one year, respectively). In the PTA category, the use of ALG/ATG (n = 109) was associated with significantly higher one-year graft survival rates than when OKT3 (n = 55) or neither (n = 8) were used (52%, 46%, and none, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Organ transplantation and the inevitable debate as to what constitutes a basic health care benefit.

Abstract: The need for health care reform is an economic reality. The urgency with which it must be pursued is apparent. The direction it will take is clear. The implications it has for transplantation are ambiguous. Managed competition will take time to implement, but managed care is here now and will surely become more prevalent. Thus, it is timely to examine the future of transplantation from the perspective of managed care. Foremost among our concerns is just how transplantation will factor into the debate as to what constitutes a basic health care benefits package. The National Cooperative Transplantation Study (NCTS) was undertaken to address a variety of clinical, economic, social, ethical, and quality-of-care issues. Based on a random sample of all transplants performed in the United States in 1988, individual assessments were made of charges for kidney, heart, liver, heart-lung, and pancreas transplantation. Insurance coverage and reimbursement policies and practices were also analyzed. In 1988 dollars Medicare procedure charges from date of transplant through date of initial discharge were as follows: kidney, $39,625; heart, $91,570; liver, $145,795; heart-lung, $134,881; and pancreas, $66,917. Both patient charges and outcomes were adversely affected by the patient's status prior to surgery, and by the need for retransplantation. The associations among transplant program activity, procedure charges, and patient outcomes varied. While insurance coverage for transplantation has steadily improved, hospital reimbursement is often well below billed charges, as a result, access for some patients may be limited. Organ transplantation is often criticized as too costly, given other health care needs. A recent report indicates that the total first-year charges for transplantation continue to increase. Estimated charges in 1993 dollars are as follows: kidney, $87,700; heart, $209,100; liver, $302,900; heart-lung, $246,000; pancreas, $65,000; and lung, $243,600. Although expensive, transplantation can be equally if not more cost-effective than other accepted therapeutic approaches for the treatment of catastrophic disease. Nonetheless, under managed care and capitated payment it will be essential that the high cost of transplantation be addressed. To reduce charges, enhance patient outcomes, and improve access patient selection policies must be reconsidered. Currently, those patients who are least likely to benefit, yet whose treatment cost the most, are given priority for transplantation. While this approach may be clinically indicated, it is socially unacceptable. Managed care and managed competition will force physicians and surgeons to adopt a more conservative and cost-efficient practice style. The patients who stand to benefit most are those whose needs are consistent with the principles of cost effectiveness.(ABSTRACT TRUNCATED AT 400 WORDS)

Thirty-year trends in clinical kidney transplantation.

Abstract: Trends in one-year graft survival rates seen in the past 30 years were examined in the UCLA and UNOS Registries. Some of the trends noted were as follows: 1. One-year graft survival rates for cadaver-donor transplants improved from 40% to 80% during this 30-year period. One-year patient survival improved from 50% to 95%. Transplants from living-related donors improved in graft survival from 80% to 90-95%. 2. Factors that diminished in importance were: recipient race, sensitization, primary disease, HLA haplotype matching in living donors, recipient and donor sex, kidney sharing, and transfusions. 3. Factors that continue to provide about a 10% variation of one-year graft survival are: cold ischemia time, HLA mismatch, recipient and donor age. 4. Posttransplantation, factors such as first-day diuresis, one-week dialysis, rejection at discharge, and discharge serum creatinine continue to be very important determinants of future outcome in 6 yearly subsets of patients. 5. Induction by ALG and OKT3 was shown in 6 subsets to have no effect on one-year graft survival. 6. Future trend studies will be needed to examine the 5-year long-term effects.

Trends in liver transplantation in the United States.

Abstract: Although the growth in liver transplantations (LTX) recorded by the Pitt-UNOS Liver Transplant Registry since October 1987 continues, the rate of increase has been declining in recent years. Among children, the number of procedures reached a peak in 1990 and declined each year thereafter. The number of centers performing LTX continued to increase. However, in 1992, compared with previous years, the greatest proportion of centers had a decreased volume of procedures, and the fewest number of new centers were opened. Upon examining characteristics of pediatric recipients from 1987 through 1992, no significant trends were noted for sex, race, age, or nationality. The distribution of functional status in 1992 was similar to that prior to 1991. Compared with recipients in the other 2 time periods, recipients in 1991 were more likely to be in the best functional status and least likely to be in the ICU. The most common indication for LTX in children was biliary atresia, though the proportion of recipients with this primary liver disease decreased significantly over the study period. Significant increases were noted in the proportions of pediatric recipients with autoimmune disease (though this remains a relatively uncommon indication) and fulminant liver failure. There have been trends in many of the characteristics examined for adult recipients. The proportion of male recipients grew significantly between 1987 and 1992. Decreasing proportions of White recipients and increases among Hispanics and Asians were found. The mean and median ages of adult recipients peaked in 1990, with a slight decrease in 1992 reflecting a slight rise in the proportion of the youngest age group and a slight decline for the oldest age group. Adult recipients had better functional status in 1991 than earlier recipients, and the distribution in 1992 was very similar to that in 1991. The trend in the proportion of recipients with positive CMV serology followed very closely the pattern in age distribution, peaking in 1991 and dropping slightly in 1992. The proportions of multiorgan recipients were similar in all 3 time periods. However, in 1992, contrasting with previous years, most multiorgan procedures involved only a kidney. Alcoholic cirrhosis continued to be the most common reason for LTX, though the combination of non-A, non-B hepatitis and hepatitis C accounted for only 20 fewer recipients. The proportions of recipients with hepatitis B and malignancies (the indications with the poorest survival) declined significantly. The cumulative probability of patient (retransplantation-free) survival 5 years after initial transplantation was 0.7 (0.58) for pediatric recipients.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of HLA matching on renal transplant survival.

Abstract: 1. HLA matching had a significant impact on cadaveric renal allograft survival. The difference in graft survival rates between the best- and worst-matched recipients among the 30,139 first cadaver transplants was 11% at one year, 19% at 3 years, and a projected 32% at 10 years posttransplant (p < 001). 2. Kidneys with no HLA antigens mismatched to the recipient yielded a superior result compared with any other match level. The one- and 3-year graft survival rates were 89% and 83% at one and 3 years, respectively. Even a single HLA antigen mismatch resulted in substantially poorer survival rates of 84% and 72% at one and 3 years (p < 0.001, each comparison). Nevertheless, there was a stepwise decline in graft survival with increasing numbers of mismatched HLA antigens. 3. The number of HLA-matched first cadaver transplants performed has increased from 2% of the total in 1987 to 6% in 1992, as a result of the national 6-antigen-match sharing program instituted by UNOS in 1987 and expanded to include phenotypically matched kidneys in 1990. 4. The incidence of early graft rejection episodes correlated with the number of HLA antigens mismatched. Only 12% of the zero-mismatched recipients experienced early rejection, whereas 26% of those with 5 or 6 antigens mismatched had rejection episodes during the transplant hospitalization (p < 0.01). 5. Transplants performed at the top 20 United States centers (based upon multivariate ranking) showed a strong effect of HLA matching, especially with respect to long-term outcome. The survival difference between the best- and worst-match groups was 9% at one year, 16% at 3 years, and a projected 25% at 10 years (p < 0.05). 6. Similarly, the survival difference between the best- and worst-matched groups at the bottom 20 centers was 16% at one year, 22% at 3 years, and a projected 36% at 10 years (p < 0.01). The bottom 20 centers apparently placed more emphasis on matching. Transplants with fewer than 3 mismatched antigens accounted for 34% of first cadaver transplants in the bottom 20, compared with 26% at the top 20 centers. 7. When all 27 possible HLA-A,B,DR mismatch combinations were examined, those involving HLA-DR mismatches had a strong influence on graft outcome at 3 months, whereas those involving HLA-B mismatches had the most influence on long-term outcome. HLA-A-locus mismatches had the smallest effect on graft outcome.(ABSTRACT TRUNCATED AT 400 WORDS)

The impact of free radical-mediated reperfusion injury on acute and chronic rejection events following cadaveric renal transplantation.

Abstract: In a prospective, randomized, double-blind, placebo-controlled trial, rhSOD was given to cadaveric renal allograft recipients intravenously in a dose of 200 mg during surgery, and its effect on both acute and chronic rejection was investigated. The results showed that rhSOD exerts a beneficial effect on acute rejection episodes as indicated by a statistically significant reduction of first acute rejection episodes to 18.5% compared with 33.3% in controls, and a reduction in early irreversible acute rejection to 3.7% compared with 12.5% in controls. With regard to longterm results, there was a statistically significant improvement in the actual 5-year graft survival rate for rhSOD-treated patients to 68% (with a corresponding 13-year half-life) compared with 50% in controls (with a corresponding 6-year half-life). The incidence of acute rejection episodes did not prove to be a risk factor for long-term graft outcome. Rather only the combination of acute rejection episodes and the presence of uninfluenced reperfusion injury appeared to have a detrimental effect on long-term prognosis. The beneficial effect of rhSOD observed in this trial is not well understood, although one can assume that the effect is brought about by interference of rhSOD with ischemia or reperfusion injury to the allograft by oxygen-free radicals. In this sense, rhSOD may mitigate increased MHC expression and presentation, cytokine-adhesion molecule expression, and APC activation induced by reperfusion injury. In addition, in accordance with the "response-to-injury" hypothesis to explain the pathogenesis of arteriosclerosis, rhSOD may mitigate acceleration of chronic obliterative rejection or arterio-/arteriolosclerosis induced by reperfusion injury. In this sense, rhSOD may act indirectly by reducing acute rejection-mediated endothelial injury, or directly, by ablation of reperfusion-mediated acute endothelial injury.

Effect of race on renal transplant outcome.

Abstract: Renal transplant outcome was compared in whites and blacks at a single center. All recipients transplanted between 1984 to 1991 were included in this study. White and black recipients were followed for a mean period of 37.6 (1-96) months. The age, sex, follow-up period, immunosuppressive protocol, number of retransplants, HLA mismatches and etiology of renal disease were comparable in the two races. Overall graft survival was lower in black recipients (p=0.0300). Graft survival in all cadaver (p=0.0520) and primary cadaver (p=0.1430) transplants was lower in blacks, though this was not statistically significant. Percentage of graft losses during the follow-up was higher in black 53/108 (49%), than white recipients 82/257 (32%)(p=0.002), as were cadaver graft losses due to rejection, 39/92 (42%) in blacks, 54/190 (28%) in whites (p=0.02). There was no significant difference in graft losses due to rejection between races in the 1 yr post transplant, but there were significantly more graft losses after 1 yr in blacks 16/83 (19%) compared to whites (16/156(10%)(p=0.05). In cadaver grafts functioning for 6 months, subsequent survival was lower in black recipients (p=0.0418). There was lower patient survival in blacks during the mean follow-up period of 37.6 months (1-96). In conclusion, lower graft survival in blacks can be partially explained by fewer LRD transplants in black recipients. Persistent lower graft survival in all black recipients and significantly more losses due to rejection beyond 1 yr may be related to immunological differences, poor compliance, or a combination of both.

Psychological adjustment of liver transplant candidates.

Abstract: The psychological functioning of 20 adult liver transplant candidates was evaluated. Using standardized assessment instruments, we found few personality disturbances and normal levels of anger. However, clinically significant levels of depression and anxiety were reported for 28% and 37% of the sample, respectively. Moreover, patients whose coping strategies were characterized by avoiding the exigencies of their illness reported more depression, more anxiety, and increased psychopathology. Disease severity was also positively correlated with anxiety and avoidant coping strategies. Implications of these findings for the pre-transplant psychological evaluation are discussed.

Immunologic monitoring during OKT3 therapy.

Abstract: The monoclonal antibody OKT3 is a potent immunosuppressant inducing both T-cell depletion and antigenic modulation of the CD3/T-cell receptor complex CD3 + lymphocytes are cleared from the circulation within 1 hour of intravenous administration of OKT3 Periodic monitoring of remaining or reappearing CD3 + lymphocytes gauges the adequacy of OKT3 dosing and OKT3 consumption by anti-OKT3 antibodies The maximum acceptable concentration of CD3 + lymphocytes for maintaining the effectiveness of OKT3 therapy remains controversial due to variable sensitivity of the methods used Intravenously administered OKT3 has a half-life of approximately 18 hours and results in trough serum levels ranging from 500 to 1000 ng/ml in 3 to 4 days The antibody response to OKT3 is oligoclonal, and both IgM and IgG antibodies to OKT3 may develop, showing restricted specificity; anti-isotypic and/or anti-idiotypic antibodies can be detected The IgG anti-idiotypic antibodies are the ones that neutralize the therapeutic activity of OKT3, and their specific detection involves the use of an immunofluorescence method that tests their ability to block the binding of OKT3 to normal T cells The production of OKT3 antibodies has been shown to be affected by concomitantly administered immunosuppressive agents Studies have demonstrated that OKT3 can be successfully reused in allograft recipients who do not present anti-idiotypic blocking antibodies The acute clinical syndrome regularly observed upon the first OKT3 injection is related to massive, although transient, release of several cytokines, which may be easily monitored with currently available radioimmunologic or immunoenzymatic tests

Surgical complications after simultaneous pancreas-kidney transplant with bladder drainage.

Abstract: The proper management of surgical complications after simultaneous pancreas-kidney transplantation is essential to minimize morbidity. The almost universal acceptance of bladder drainage has shifted the complications after pancreatic transplantation from intra-abdominal to urologic. Most urologic complications will respond to conservative therapy. However, the early conversion to enteric drainage can be safely utilized when conservative therapy fails.

Clinical and socioeconomic benefits of serological HLA-DR matching for renal transplantation over three eras of immunosuppression regimens at a single unit

Abstract: The efficacy of HLA-DR matching in cadaveric renal transplantation is controversial in the cyclosporine (CsA) era. Reports have questioned both the reliability of serological HLA-DR typing as well as the benefit of matching in terms of improved graft survival. Analysis of 1,000 consecutive cadaver donor transplants performed at Oxford between 1975 and 1992 has shown that with improved immunosuppressive regimens and increased transplant success there has been a steadily diminishing influence of HLA-DR matching measured in terms of first graft outcome. For patients treated with azathioprine and prednisolone (n = 278) overall one-year first graft survival was 65%, but there was a 20% improvement associated with HLA-DR matching which has been maintained for up to 15 years. With the introduction of CsA, used either alone or in conjunction with low dose steroids (n = 96), one-year first graft survival was 69% and the difference between HLA-DR-matched and -mismatched transplants was 14%. Our current maintenance immunosuppressive protocol is triple therapy (N = 425) with an 81% one-year first graft survival for both matched and mismatched transplants. However, we do continue to find a marked correlation between HLA-DR matching and clinical course. HLA-DR-mismatched patients suffer more rejection episodes, spend a longer time in the hospital, and have higher creatinine levels at 3 months. This costs, on average, an extra 1,500 pounds for each mismatched transplant. The effect is most apparent in unsensitized males. For cadaveric regrafts, one-year graft survival for patients on triple therapy is 80% (n = 116) which does not differ from first graft survival rates.

Donor factors in cadaveric renal transplantation.

Abstract: 1. Donor kidney side (left/right) had no significant effect on cadaveric renal allograft survival. 2. Kidneys from male donors had an 83% one-year graft survival rate, compared with 78% for those from female donors. 3. Donor race did not have an effect on renal allograft survival. 4. One-year survival rates for kidneys from very young ( 50 years old) cadaver donors (74%) were significantly poorer than those for kidneys from donors age 6-50 (84%). 5. Donor ABO blood type and Rh factor had no significant effect on renal allograft survival. 6. Cause of death (trauma/nontrauma) had a pronounced effect on cadaveric renal allograft survival. Kidneys from trauma donors (motor vehicle accident, gunshot wound, head injury, etc.) had a significantly higher one-year graft survival rate (84%) than that of kidneys from nontrauma donors (77%). This effect was found to be independent of donor age. 7. Donor past medical history had a significant effect on renal allograft survival. Kidneys from donors with histories of hypertension had slightly poorer graft survival (75%) than those from "normal" donors (80%). Donors with histories of diabetes had significantly lower graft survival; 54.8% at one-year posttransplant. 8. Donor lifestyle factors, including smoking, drinking, drug use, and sexual history, had no significant effect on renal allograft survival. 9. The duration of donor hospitalization (from admission to the time of procurement) had no effect on renal allograft survival. 10. Donor cardiac arrest (in either the field, hospital, or operating room) had no significant effect on renal allograft survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Cadaver-donor renal retransplants.

Abstract: 1. There was a dramatic improvement in survival rates for retransplanted patients between 1989 and 1991. The proportion of cadaveric kidneys used to retransplant patients has decreased from 18.4% in 1984 to 14.3% in 1992. In 1992, the 81% one-year survival rate for second transplants nearly reached that of first transplants. 2. Despite recent improvements in regraft survival, the PGST remained the strongest predictor of second graft outcome. One-year regraft survival rates were 54% when the PGST was one to 3 months and 75% when the PGST was more than one year. The steady improvement in second graft survival rates may be influenced by retransplanting more patients with a longer PGST. 3. Patients with broadly reactive anti-HLA antibodies (PRA > 50%) had 10% lower regraft survival rates than nonsensitized patients (p < 0.001). 4. A repeated HLA-DR antigen mismatch resulted in 6% and 13% lower regraft survival at one and 3 years, respectively, compared with patients who had at least one HLA-DR mismatch, but not for the same antigen mismatched previously (p < 0.05). 5. Recipients expressing HLA-DR1 had an 81% one-year second graft survival rate compared with 75% for patients lacking DR1 (p < 0.001). 6. Matching for HLA-B,DR and HLA-A,B,DR antigen combinations resulted in 80-82% one-year regraft survival rates for second and multiple transplant recipients, compared with 57-74% for completely mismatched transplants. 7. Transplants from donors under age 6 or over age 55 had significantly poorer outcomes than those involving kidneys from donors in the intermediate age range. The results of transplants at the extremes of donor age were very poor when the recipient was retransplanted. 8. Among recipients of second and multiple transplants, prophylactic OKT3 yielded 82% and 72% one-year regraft survival, respectively, compared with 75% and 66% with no antibody induction (p < 0.001 for second transplants). 9. Regraft survival rates comparable with those for primary cadaveric transplants reported to the UNOS Registry since 1991 justify the use of cadaver-donor kidneys for low-risk patients seeking second renal transplants.

Baylor update: outcome analysis in liver transplantation.

Abstract: An analysis of the first 740 liver transplants performed at Baylor is presented, including all cases to the end of calendar 1992. Kaplan-Meier curves are extended to nine years posttransplant. Our focus on outcome analysis has led us to review our experience with diabetics, with elderly patients, causes and patterns of late graft loss, long-term renal function. Quality of life data tracked for 2 years posttransplant is outlined. Clinical correlates to whole blood and plasma assays of FK506 are reviewed. Concerns remain over the disappointing results of liver transplantation for cholangiocarcinoma and those of patients with hepatitis-B antigenemia under current protocols.