Showing papers in "Clinical Transplantation in 1988"

Long-term survival.

Abstract: 1. In transplants performed between 1971 and 1986, first cadaver donor grafts had a half-life ranging from 6.6 to 7.5 years in the period after the first year. Second cadaver donor grafts had a half-life of 5.1 to 6.5 years. Parental donor grafts had a half-life of 9.3 to 11.8 years, whereas HLA identical sibling donor transplants had a half-life of 19.1 to 26.5 years. Siblings with no haplotype in common had an average half-life of 8.7 years. 2. Between 1971 and 1984, white recipients had an average half-life of 7.7 years, which increased to 9.3 years in 1985-1986. Black recipients' half-life decreased from 5.4 years in 1975-1976 to 3.5 years in 1985-1986. The reason for this decrease is not apparent. 3. The half-life of transplants of different recipient ages did not vary significantly. The average half-life during this period of study was 7.4 years for those younger than 21 years of age, 8.2 years for recipients 21 to 50 and 6.7 years for those older than 50. 4. In the early data, there was some evidence that the half-life of kidneys with cold ischemia below 13 hours was superior. However, in the latest period (between 1983 and 1986) the average half-life was 7.6 years for CIT below 13 hours, 7.2 years for those with 13 to 24 hours and 6.4 years for more than 24 hours. 5. For patients receiving kidneys with no HLA-A,B mismatches, the average half-life was 10.1 years. Those with A,B mismatches had a half-life of 6.7 years, and for those with no A,B antigens in common, the average half-life was 6 years. 6. In the period after 1981, the average half-life of patients with no A,B,DR mismatches was 9.1 years compared with 6.5 years for those with A,B,DR mismatches and 5.4 years for those with no A,B,DR antigens in common.

Donor age and recipient age.

Abstract: Donor age. 1. Kidneys from older donors led to markedly lower graft survival than kidneys from younger donors. The 1-year first cadaver donor graft survival rates were 80% for recipients receiving kidneys from 16-year-old donors, 70% from 50-year olds and 57% from 65-year-old donors. This means that 1-year graft survival decreased 10% by donor age 50 and 23% by donor age 65. 2. The trend toward lower graft survival with older donors was most noticeable after 1985, suggesting that CsA treatment was primarily responsible for the effect. 3. Twelve percent of kidneys from donors over age 50 never functioned while the nonfunction rate of 17- to 30-year-old donor kidneys was only 2%. Forty-six percent of kidneys from younger donors functioned within 3 days, whereas 26% functioned in 3 days if they came from donors who were older than 50. 4. The tendency to use older donors has gradually increased in the past 10 years. Donors over 50 years of age comprised 5% of the donors in 1978 and rose to 10% by 1987. 5. Transfusions, HLA-B,DR mismatches, and causes of failure were not related to donor age. 6. In transplants performed in the last 10 years, donor age did not play a significant role in either patient or graft survival. Whether or not this will hold true for more recent CsA-treated transplants remains to be seen. Recipient age. 1. The most significant effect of recipient age for patients transplanted since 1983 was on patient survival: it dropped from 100% for 6- to 7-year-old recipients to 86% for 68- to 71-year olds. 2. There is an increased tendency to transplant patients older than 50. The number rose from 14% in 1978 to 25% in 1987. 3. A very strong association was noted between advancing recipient age and corresponding decrease in immunologic failures and increase in nonimmunologic failures. Immunologic responsiveness to allografts decreased with age, though failures from nonimmunologic causes increased with age. 4. Patients with no transfusions had increasingly higher graft survival with age: 63% 1-year graft survival for patients up to 20 years old and 73% for those over 50 which was consistent with the above findings. Transfusions led to 1-year graft survival of about 76% in all groups. Thus, transfusions had less effect in older recipients.(ABSTRACT TRUNCATED AT 400 WORDS)

Alloreactive t lymphocytes cultured from liver transplant biopsies: associations of hla specificity with clinicopathological findings.

Abstract: Lymphocyte cultures grown from liver allograft biopsies were shown to exhibit alloreactivity towards donor cells as measured by primed lymphocyte testing (PLT). The PLT specificity was determined in assays using HLA typed panel cells and/or by inhibition testing with HLA specific monoclonal antibodies. Certain cultures exhibited PLT specificity towards class I HLA antigens of the donor, whereas others were specific for class II HLA antigens or recognized mixtures of class I and II antigens. These PLT specificity patterns were compared with clinical, histological and laboratory findings on the liver transplant patients at the time of the biopsy. Biopsies yielding class I specific PLT cells were taken generally during the earlier posttransplant period, whereas class II specific cells were grown from later biopsies. There was no significant correlation of the PLT specificity towards class I vs II antigens with the levels of total or direct bilirubin, serum glutamate oxaloacetic transaminase (SGOT), and serum glutamate pyruvate transaminase (SGPT), although a trend towards higher values was noted for biopsies presenting with a class II specific infiltrate. However, the levels of gamma glutamyl transpeptidase (GGTP) and alkaline phosphatase (AP) were significantly increased when biopsies yielded class II specific rather than class I specific PLT cells. Biopsy histology showed more damage to bile duct epithelium in association with class II PLT specificity whereas intense but often reversible infiltrates were found in biopsies yielding class I specific cells. The elevated GGTP and AP levels are probably related to the interaction of class II specific T cells with bile duct epithelium, which has been shown to express induced class II HLA antigens on their cell surface.

Significance of the HLA molecular structure to transplantation.

Abstract: 1. Residues in the first, second, and third domains of HLA-A,B,C, and the first domain of DR beta, DQ alpha, and DQ beta molecule have been assigned to unique A,B,C or DR specificities from the known amino acid sequences. Antibodies were noted to correlate with most of these variable amino acid residues. 2. We therefore conclude that most of the variable residues in the first domain function as immunogens against which the antibodies had been elicited. 3. If the variants at these positions are immunogens, then it follows that matching for transplantation should be done by considering mismatched amino acids rather than the private specificities, as performed today. 4. Molecular matching cannot be performed immediately for the HLA-A,B,C specificities since many specificities are not yet sequenced. For the DR and DQ specificities, the sequences are established, but antisera identifying the subtypes of DR and DQ are only now becoming available. Once patients are typed for the 23 DR beta alleles, 8 DQ alpha alleles and 13 DQ beta alleles, matching should be feasible. 5. Molecular matching combines both public and private specificity matching since it assumes that both types of antigens are distinct. A single extended DR mismatch may involve as many as 76 amino acid residues of mismatch. 6. True cross-reactivity of the HLA molecules can eventually be established through structural studies. Most of the previously described "cross-reactivities" are likely to be shared determinants.

Donor and preservation factors.

Abstract: 1. In nonsensitized, white recipients of first cadaver donor transplants, 1-year graft survival was: 13% lower when the donor was black than when the donor was white; 7-9% lower when the kidney was from a pediatric (under 15) or older (over 50) donor than from a donor aged 21-50; 8% lower when the donor was a female over 30 than when the donor was a male under 30; 4% lower when the cause of donor death was a cerebrovascular accident than when the death was a closed head injury; 6% lower when the kidney was transplanted with more than 36 hours of cold ischemia time than when ischemia was less than 24 hours; 3% lower if the kidney had been transported more than 50 miles to the transplant center. 2. The lower graft survival rates associated with the race, sex, age and cause of death of the donor were generally reflected in a higher incidence of early nonfunction and poorer quality of function. 3. Preservation related factors, long cold ischemia and sharing were associated with an increase in delayed onset of function, but there was no difference in the proportion of kidneys that never functioned during the follow-up period. 4. There was a 9% difference in 1-year graft survival between kidneys obtained from centers more than 50 miles from the transplant center and with more than 36 hours of cold ischemia and those transplanted locally with less than 24 hours of cold ischemia. 5. Long cold ischemia, even in excess of 48 hrs, had no effect on graft survival when the kidney was procured locally. Long cold ischemia in the absence of sharing was not an apparent risk factor. 6. Rather than concluding that distant sharing results in kidneys of poor quality, we may have to consider that kidneys of poor quality are sometimes shared. 7. Cadaver kidneys from female donors over 30 had 80% 1-year survival when transplanted to recipients who weighed between 41 and 75 kg, a result comparable to that obtained with young male donor organs. In recipients over 75 kg, survival of the older female kidneys was 70% vs 80% for young male donor kidneys. Recipient "size" may be a nonimmunological risk factor.

The effect of mismatching and sharing of HLA-A, -B, and -DR antigens on kidney graft survival in Eurotransplant 1982 to 1988.

Abstract: 1. Cyclosporine significantly improved kidney graft survival by 10-15%. 2. Matching for HLA-DR, HLA-B + DR and HLA-A + B + DR improved kidney graft survival significantly in non-CsA-treated patients. 3. Matching for the HLA-A, -B, and -DR loci, apart and in combination, significantly improved kidney graft survival in CsA-treated patients. 4. The best kidney graft survival was observed in HLA-A + B + DR identical combinations treated with CsA (76% at 5 yrs).

The International Society for Heart Transplantation Registry.

Abstract: The Registry for the International Society for Heart Transplantation has collected data on some 6,500 heart transplant recipients and 344 heart-lung recipients. Operative mortality in heart transplantation has decreased substantially since 1985. There has been a recent increase in cardiac complications following heart transplantation. Congenital heart disease is a significant risk factor in heart transplantation. More patients are undergoing heart-lung transplantation for cystic fibrosis. Improved survival is seen with triple-drug immunosuppression in both heart and heart-lung recipients.

Living donor kidney transplants.

Abstract: 1. Whites showed an increase in graft survival in the 2-haplotype matched transplant recipients compared to black recipients at 1-, 2-, and 3-years posttransplant. The difference was not found in the Asian population. Comparing 1-versus 2-haplotype matched transplants showed an increasing statistical significance at yearly intervals, indicating that there was increased HLA chromosome matching effect at 2 and 3 years. Additionally, 2-haplotype matched transplant regrafts showed similar results to first grafts; however, 1-haplotype matched regrafts did poorly relative to 1-haplotype matched first grafts. 2. Living nonrelated transplants and 0-haplotype matched transplants did well initially at 1-year graft survival but there was a decrease in graft survival in these transplant groups at 2 and 3 years. 3. Sensitized patients who received transplants from their mother or father showed an increase in transplant survival in the former and decreased transplant survival in the latter. This may be associated with the exposure in utero of the recipient to the noninherited maternal antigens, thus allowing the better graft survival with the mother as the donor. 4. Cyclosporine showed little effect on graft survival with the exception of a statistically significant difference only in 1-year graft survival for 1-HLA haplotype matched transplant recipients. However, an inverse effect was noted for mother-to-child transplants where CsA treatment showed statistically significant poorer transplant survival a 1 and 2 years. 5. In 1-haplotype matched transplants, neither random transfusion nor donor-specific transfusion exerted much effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Shortage of kidneys, a solvable problem? The Leuven experience. Leuven Collaborative Group for Transplantation.

Abstract: Our 10-year experience with the LCGT indicates that close collaboration of nephrologists from peripheral centers for the long-term follow-up of transplanted patients presented no obstacles to excellent patient and graft survival rates. At the same time, "decentralization" greatly increased the motivation of collaborating centers to participate in organ procurement. In addition, the introduction of an "opting out" law provided spectacular stimulation for collaborating center participation. For the first time in many years, the number of transplants was higher than the number of new candidates registered on the waiting list.

Organ sharing for good HLA-A,B, and DR matching improves cadaver renal graft survival in SEOPF: retrospective and prospective studies considering delayed graft function, race, center effects, cyclosporine, and other factors.

Abstract: 1. HLA matching is associated significantly with factors including CsA use, ALS use, recipient race, prior graft loss, presensitization, preservation time and most strongly, with organ sharing. However, HLA match is not directly associated with delayed graft function. 2. By univariate and multivariate analyses, good HLA matching provides significant benefits in graft survival regardless of CsA use, organ source or other potentially confounding factors. 3. HLA-A,B, and DR matching have independent and essentially equivalent benefits on graft survival in CsA-treated patients, whereas HLA-A,B matching has a greater benefit in non-CsA-treated patients. 4. Organ sharing, per se, provides no direct detrimental effect on graft survival by univariate or multivariate analysis. 5. By multivariate and univariate analyses, shared/well-matched kidneys provide significantly better graft survival than local/poorly matched kidneys. 6. Delayed graft function is associated in a complex relationship with organ sharing, prior graft failure, presensitization, and CsA use. 7. The increased rate of delayed graft function associated with organ sharing is overcome by the benefit of good HLA matching. 8. Since April 1986, purposeful organ sharing at SEOPF centers for good HLA matching has been associated with improved graft survival, especially in patients at high risk due to presensitization or prior graft failure.

Kidney transplant mortality relationships.

Abstract: 1. Patient mortality for adults was described by the sum of 3 components of risk: age-dependent risk; transplant-dependent risk, depending on time after first transplant; and failure-dependent risk, depending on time after failure. 2. The age-dependent risk increased exponentially at a rate about two-thirds the rate of increase in the general population. This risk was about twice as large for recipients of cadaver kidneys as for those who received grafts from HLA-identical siblings; the risk for recipients of parent donor grafts was intermediate. The risk for transplant recipients was much larger than that for the general population over most of the age range. 3. The transplant-dependent component decreased exponentially with the time after transplant and was reduced by half after about 2.25 years. The component was about 4 times as large for recipients of cadaveric kidneys as from HLA-identical sibling donors. Since patients studied were limited to those who survived at least 3 months after transplant, the transplant-dependent component of risk, as defined, does not represent the larger and more rapidly decreasing loss that occurs within a month or two after transplant. 4. The failure-dependent component was large and decreased exponentially with time after graft failure; the risk was reduced by half in about 7.5 months. For recipients of cadaveric organs, "excess" of death in the first year after failure was about 10%--slightly more than percent excess death as in the first year after transplant. In the case of diabetics, the excess deaths in the year after failure was about 25%. 5. Life expectancy at various ages at transplant was calculated from the estimates of risk of death. The maximum loss for males transplanted from HLA-identical siblings was about 10 years. The maximum occurred at age-at-transplant 20 years; life expectancy for patients transplanted at that age was about 42 years. Perhaps 5% to 10% of patients transplanted at age 20 from cadaveric donors might expect to survive into their 80's. 6. Survival analysis with allocation to graft failure of patient-death-with-functioning-graft fractionally (according to probability that the death was transplant related) provided a method of adjusting for patient age in studying graft survival. In younger patients, death was most likely attributable to the transplant, whereas in older patients, death was likely not attributable to the transplant. 7. Appropriate attribution of patient death to graft failure is important to the study of long-term graft survival, particularly among older patients.(ABSTRACT TRUNCATED AT 400 WORDS)

A longitudinal assessment of the health status of diabetic and nondiabetic renal transplant recipients.

Abstract: This paper compares the health status of diabetic and nondiabetic renal transplant recipients. Data for the analysis were collected from 396 patients who received cadaveric transplants at 5 transplant centers in the United States. Health status was measured at several points in time, from 3 months to 15 months following transplantation. In addition to using several measures of perceived health status, 2 standardized health status measures--The Sickness Impact Profile and the Nottingham Health Profile--were used. The results of the study indicated that the health status of diabetic patients is lower than that of nondiabetic patients. Not surprisingly, nondiabetic patients are more satisfied with their health than are diabetic patients. The results of the study also showed that the health status of both diabetic and nondiabetic patients improves over time. However, with the exception of work disability, the improvement in the health status of transplant patients during the period from 3 to 12 months posttransplant is much greater for diabetic patients than for nondiabetic patients.

Changing perspectives on liver transplantation in 1988.

Abstract: After liver transplantation for cancer, there is a high incidence of disease recurrence within 18 to 36 months for most tumors, although there are a small number of long-term survivors. An extended resection of the upper abdominal viscera with replacement by a liver-pancreas cluster is being tried in Pittsburgh for lesions which have not been successfully managed with liver transplantation alone. Despite a high incidence of graft reinfection after liver transplantation for hepatitis B virus (HBV) related disease, a significant proportion of patients achieve long-term survival. Hyperimmune globulin and interferon have been of little benefit in preventing reinfection. Clinical trials with a human monoclonal antibody to HBsAg are in progress. Transplantation for alcoholic liver disease has been considered controversial. However, survival after liver transplantation for Laennec's cirrhosis is comparable to survival after liver transplantation for other chronic, benign, and non-HBV related liver diseases. Sclerotherapy followed by liver transplantation is the treatment of choice for patients with acute hemorrhage from esophageal varices and end-stage liver disease. Sclerotherapy alone or followed by selective shunting is an appropriate alternative in patients with good hepatic reserve. Only 25% of infants with biliary atresia benefit from portoenterostomy. To meet the demand for small infants waiting for transplantation, several transplant programs have successfully expanded their efforts to use partial (reduced) liver grafts. Cyclosporine and low-dose prednisone remain the basis for immunosuppression after liver transplantation. However, nephrotoxicity and hypertension are frequent and troublesome side effects of cyclosporine. Triple and quadruple drug regimens have been increasingly popular in an effort to minimize cyclosporine toxicity. Phase 1 clinical trials with a new drug, FK506, recently began in Pittsburgh. Hyperacute rejection of the liver has been demonstrated in animal models and has been strongly suspected in recent clinical descriptions of acute hemorrhagic necrosis after liver transplantation. So far, only transplantation across an ABO incompatibility has been identified as a risk factor for hyperacute rejection. The new preservation solution developed by Belzer and associates at the University of Wisconsin has significantly extended the preservation time for liver grafts, and improved the quality of liver preservation.