Showing papers in "Clinical Transplantation in 1986"

Early Graft Function

Abstract: 1. Most of the first rejections occurred between the first and third weeks after transplantation, with the peak at 7 days. 2. Average serum creatinine values of 2 mg/dl were achieved in 2 days for living-related donor transplants. Cadaver donor grafts reached an average of 4 mg/dl by the tenth day, but in patients without rejection serum creatinine values of almost 2 mg/dl were achieved. 3. Cadaver donor grafts with cold ischemia times less than 12 hours led to the best early serum creatinine values. Cold ischemia times up to 48 hours and possibly beyond led to slightly higher creatinine levels but did not produce damage in proportion to the cold ischemia time. 4. Patients who were sensitized to more than 50% of the panel showed evidence of sensitization by having higher serum creatinine levels from one week to 3 weeks. 5. Even in the first few days after transplantation with a cadaver donor, black recipients had a higher serum creatinine than white recipients. The donor's race did not have a marked effect. 6. CsA doses given to cadaver donor recipients were about 2-4 mg/kg higher than living-related donor transplants. Patients experiencing a rejection episode were found to have been treated with about 1 mg/kg more than those without rejections. The corresponding blood levels of CsA were higher in the cadaver donor grafts and those with rejections. 7. Early serum creatinine levels were very strongly correlated with the one-year graft survival rate. Even one day after transplantation, the difference between patients with the best and worst one-day serum creatinine levels was as much as 30% in the one-year graft survival rate. At 2 weeks, the group with the best serum creatinine had a one-year survival rate that was 50 percentage points higher than the worst creatinine group. At one month, the best serum creatinine group had a one-year survival rate that was about 80 percentage points higher than the worst serum creatinine group. 8. Patients with high CsA levels of over 400 ng/ml in the early one-month posttransplant period, had poorer one-year graft survival than those with lower levels. The optimum level appeared to be less than 100 ng/ml by the tenth day and about 100-200 ng/ml to the third week posttransplant.(ABSTRACT TRUNCATED AT 400 WORDS)

Crossmatching with B and T cells and flow cytometry.

Abstract: 1 Hyperacute rejections occurred in 06% of 19,415 first cadaver donor grafts and 19% of 4,326 regrafts When grouped into those without preformed cytotoxins, 05% first grafts and 13% of regrafts had hyperacute rejection Among patients with cytotoxins 13% of first grafts and 26% of regrafts had hyperacute rejections 2 A total of 923 first cadaver donor transplants and 238 multiple transplants were crossmatched by 6 variations of microcytotoxicity tests: standard, long 4-hour incubation, B lymphocytes at 4 degrees C and 37 degrees C and T lymphocytes at 4 degrees C and 37 degrees C All crossmatching was done in one laboratory 3 For first cadaver donor transplants, 178 patients with long positive crossmatches and 56 patients with T warm positive crossmatches had a significantly lower survival rate than crossmatch negative patients Those with short positive (weak), B warm, B cold, and T cold positive crossmatches had the same graft survival as crossmatch negative patients 4 In regrafted patients from cadaver donors those with a short and T warm positive crossmatches had lower graft survival than crossmatch negative patients 5 Preformed T warm cytotoxins were associated with lower graft survival in first grafts and B warm cytotoxins were associated with lower graft survival in regrafts 6 Eight patients with T warm positive crossmatches were successfully transplanted (function at 3 months) after they were shown to have IgM antibodies removable by 2-ME treatment 7 A total of 136 patients were tested by FCXM at the time of transplant on a retrospective basis Although all patients were crossmatch negative by the T warm tests, 24 were FCXM positive(ABSTRACT TRUNCATED AT 250 WORDS)

Factors important in 10-year kidney transplant survival.

Abstract: We reviewed 14,005 renal grafts with the temporal opportunity for 10-year survival (transplanted 1975 and earlier) and analyzed 10-year actuarial graft survival and the rate of late (3- through 10-year) graft loss as reflected by half-life. The 10-year graft survival for first transplants in HLA-identical siblings was 67% versus 38% for parental donors and 20% for cadaver donors. Factors with substantial influence on 10-year graft survival include transplant number, transfusions (0, 17%; greater than or equal to 1,33%), HLA-A,B mismatches (0, 29%; 1-2, 20%, 3-4, 17%), cold ischemia time (0-3 hours, 32%; 4-6 hours, 27%; 7-12 hours, 21%; greater than 12 hours, 16%), preservation method if CIT is no more than 24 hours (cold storage, 22%; machine, 17%), recipient race (Caucasian, 23%; black, 11%), original disease, recipient age, recipient sex, donor race, and the quality of early graft function (less than or equal to one month). Factors not significantly influencing 10-year graft survival were panel-reactive antibodies, warm ischemia time, preservation method if CIT was more than 24 hours, and donor sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Regraft kidney transplant survival.

Abstract: The salient features of one-year regraft transplant survival are as follows: 1. The effect of cyclosporine is less (about 7% increase in one-year graft survival) on regrafted patients than on first grafts. 2. In general we saw a HLA antigen matching effect in cyclosporine- and noncyclosporine-treated retransplant patients. 3. Patients who received living-related HLA two-haplotype matched kidneys did equally as well as a first or regraft recipient. 4. Transfusions seemed to have a minimal effect on regraft survival. 5. It is more important to match in patients who have PRA and the matching benefits translate into 61% and 75% one-year graft survival for zero DR and zero B,DR mismatched regraft patients, respectively. 6. In regrafts, female donor kidneys resulted in 15% lower one-year graft survival than male donor kidneys. 7. Retransplant patients from fair centers showed a significant 13% increase in one-year graft survival with cyclosporine. 8. Cold ischemia time, diabetes, and kidneys used locally or shipped had little effect on the regraft one-year survival. 9. The initial function of the retransplant kidney had a very large effect on the final one-year graft outcome of that kidney and was independent of the use of cyclosporine patients having a functioning kidney at one month had 75% and 72% one-year regraft survival with and without cyclosporine treatment, respectively. Patients having a nonfunctioning kidney at one month had 5% and 8% one-year regraft survival with and without cyclosporine treatment, respectively. 10. Responder and nonresponder classifications as defined by the duration of the first graft resulted in a 10 to 15% difference in regraft survival. 11. The effect of HLA-A,B matching was very strong in responder patients, i.e., there was a 32% difference in one-year regraft survival between zero mismatch and more than two antigens of mismatch. In nonresponder patients, the effect of HLA-A,B matching was only 5%. For HLA-DR locus matching, the difference was 12% for responders and 6% for nonresponders. 12. Cyclosporine use showed about a 10% increase in graft survival in responders and nonresponders. 13. Responder classification was also possible by separating patients who had initial function but no function at one month (responders) from those with function at one month (nonresponders).

Donor and recipient age effect.

Abstract: Donor Age 1. Kidney graft survival rates from donors who were younger than 5 have not improved substantially during the 10 years; approximately 40% one-year graft survival in 1975 to about 50% in 1985. On the other hand, grafts from donors 6 years and older have improved from about 40% to 75% in 1985. Most notable has been the marked increase in graft survival rates from donors who were older than 59 years. 2. Cyclosporine seems to adversely affect graft survival from older donors. Thus the improvement is greater for kidneys from young donors than from donors who are 55 or older. 3. Female donors. older than 20 years of age resulted in one-year graft survival rates that were about 10% lower than for kidneys from comparable-aged male donors when cyclosporine was used. 4. The first day nonfunction rate and the one-month nonfunction rates for cyclosporine-treated patients were higher than for conventional treatment in the older age kidneys. Thus some of the effect of cyclosporine in the older kidney takes place within the first month. 5. Grafts from donors under 9 years of age were more frequently reported to have failed due to immunologic failure than grafts from older donors. Kidneys from donors younger than 3 had the highest immunologic failure rate as well as the highest technical failure rate. Even for recipients younger than 3, it appears that older donor kidneys succeed at a higher rate. Recipient Age 1. Recipients of all ages over 6 have approximately the same graft survival rates.(ABSTRACT TRUNCATED AT 250 WORDS)

The roles of sex, race, and ABO groups.

Abstract: 1. Recipient sex did not play a significant role in transplant outcome. 2. Donor sex emerged as a surprisingly major factor in recent transplants. Cyclosporine did not increase graft survival of female donor kidneys from donors between the ages of 31 and 50 above survival rates achieved by conventional immunosuppression. Male kidneys had a 7% higher one-year survival rate than female kidneys in first cadaver transplants and a 13% higher one-year survival rate in regraft recipients treated with cyclosporine. 3. Female donor kidneys had poorer early function rates in cyclosporine-treated patients. The first day nonfunction rate was 27% in first cadaver recipients of female donor kidneys and 19% for male donor kidneys. Among recipients whose kidneys did not function in the early posttransplant period, recipients of female donor grafts had higher average serum creatinine levels than recipients of male donor grafts. 4. The poorer survival and early function rates of female cadaver donor kidneys were also affected by the age of the donor in first transplant recipients. Kidneys from females less than 30 years old survived as well as male donor kidneys, suggesting that the effect was not strictly sex-associated. 5. Matching for HLA-A,B antigens abrogated the effect of donor sex. Graft survival was the same for both male and female kidneys when no HLA-A,B antigens were mismatched between the donor and recipient in first cadaver, cadaver regraft, and living-related donor transplants. Mismatches at HLA-A,B reduced survival of female donor grafts in patients who were retransplanted by as much as 25% at one year, while male donor grafts were much less affected. 6. Black recipients had significantly lower graft survival rates than white recipients of first cadaver donor transplants. Although cyclosporine improved graft survival in blacks, there remained a 10% discrepancy between the survival of transplants in black recipients and in white recipients. 7. Although the number of transplants was small, there was no apparent race effect in blacks who were retransplanted with a cadaver donor kidney or who received a transplant from a living related donor when cyclosporine was used. 8. The poor graft survival of black donor kidneys transplanted to white recipients was due in part to very poor HLA matching. 9. The black donor kidney showed a striking similarity to the older female donor kidney in recipients treated with cyclosporine. There may be an association between cyclosporine nephrotoxicity or rejection and kidneys from hypertensive donors. 10. There were no differences in graft survival between recipients of the various blood types in recent transplants.(ABSTRACT TRUNCATED AT 400 WORDS)

Current status of allogeneic bone marrow transplantation: a report from the International Bone Marrow Transplant Registry.

Abstract: Bone marrow transplantation is widely used to treat hematologic, immune, and genetic diseases. More than 9,500 transplants have been performed by 199 transplant teams worldwide; 162 are currently active. The annual rate of allogeneic bone marrow transplants now exceeds 2,500 plus more than 1,000 autotransplants annually. Transplantation is an effective therapy for acute leukemias; in some instances, it is the preferred treatment. In chronic myelogenous leukemia, aplastic anemia, and some genetic and immune diseases, bone marrow transplantation provides the only possibility for cure. Bone marrow transplantation remains investigational in many conditions and is associated with substantial problems such as GvHD, interstitial pneumonitis, and the requirement for an HLA-identical donor. Recently an increasing number of transplants have been performed using HLA partially or fully matched, related or unrelated donors with some success. The development of GvHD and interstitial pneumonitis can, to some extent, be predicted by risk-factor assessment. Although GvHD can be prevented by depleting T cells from the donor bone marrow, this is associated with an increased risk of graft rejection and leukemia relapse. Interstitial pneumonitis can be modified by prophylaxis with CMV-immune globulin and by the use of CMV-negative blood donors. In this report, we summarized data from the International Bone Marrow Transplant Registry concerning allogeneic bone marrow transplantation in man.

The changing role of HLA matching.

Abstract: 1. In the precyclosporine era, there was a 12% difference in graft survival at one year between recipients of HLA identical and one-haplotype mismatched transplants from living-related donors. This difference increased to 20% at 5 years. 2. Recipients of cadaver donor transplants which were not mismatched at HLA-A,B antigens had a 10% higher graft survival rate at one year than recipients of kidneys which were completely mismatched at HLA-A,B. The difference increased to 17% at 5 years. 3. Patient survival at 5 years posttransplant was 5% higher in recipients of HLA-A,B matched grafts than in recipients of completely mismatched grafts. 4. The percentage of zero HLA-A,B mismatched grafts which functioned was 7% higher at one day and 10% higher at one month than completely mismatched grafts to sensitized recipients. 5. Sensitization following a rejected transplant occurred two to three times more frequently in recipients who rejected an HLA-A,B mismatched graft and were subsequently retransplanted. 6. Sensitized recipients generally received transplants which were better matched for HLA-A,B antigens as a result of selection against mismatches at the crossmatch. Twenty percent of highly sensitized recipients were transplanted with no mismatches at HLA-A,B. HLA-DR matching was not affected by sensitization. 7. HLA-C locus antigens were typed in 30% of donors and recipients since 1979. Matching for the C locus antigens in addition to HLA-A,B or HLA-DR antigens did not improve graft survival. 8. The number of patients typed for HLA-DR antigens has steadily increased since 1978, with 90% of patients transplanted in 1984 and 1985 typed for DR antigens. 9. Since the introduction of cyclosporine, there has been a significant increase in the number of poorly matched transplants at the expense of well-matched transplants. This trend coincided with a decrease in the number of cadaver donor kidneys shared between distant centers. 10. Matching for HLA-B and -DR locus antigens had a larger effect on cadaver kidney graft survival than matching for HLA-A,B or HLA-DR antigens separately. First cadaver transplants with zero HLA-B,DR antigens mismatched had a 90% one-year graft survival rate when the recipient received cyclosporine. One approach toward increasing the number of such well-matched transplants would involve extensive sharing of kidneys from B locus homozygous donors, since these account for half of the zero HLA-B,DR mismatched transplants.(ABSTRACT TRUNCATED AT 400 WORDS)

Donor-specific transfusion.

Abstract: 1. Since 1982, approximately 25% of recipients with living donor grafts were treated with DST. 2. With DST the one-year graft survival was 95% with HLA-identical siblings, 86% with parental donors, 92% with offspring, 87% with one-haplotype different siblings, and 85% with zero-haplotype different siblings. These rates were 2 to 11% higher than with comparable non-DST transplants. 3. At 3 years the parental donor transplants with more than three DST had the highest survival rate of 82% followed by greater than 3 RDT with a 76% survival rate which was considerably higher than the 3-year survival of 63% in nontransfused parental donor grafts. 4. The 3-year survival rate of DST HLA-identical sibling donor grafts was 83% but randomly transfused patients had a 90% 3-year survival in contrast to 79% in patients without transfusions. 5. Cyclosporine treatment did not significantly improve graft survival in parental donor grafts except in the zero transfusion group (from 73 to 85% at one year). Sibling donor and HLA-identical donor grafts were improved slightly by cyclosporine treatment.

Cyclosporine and trends in kidney transplantation.

Abstract: 1. In the past 4 years there has been a definite trend to increase the number of first cadaver transplants using cyclosporine. In 1985, three fourths of the patients were treated with cyclosporine. 2. One-day, one-week, and one-month function data show that there is no increased nonfunction associated with the use of cyclosporine, and in those cases with a nonfunctioning kidney, one-year survival is higher with cyclosporine treatment compared with those patients who are not treated with cyclosporine. 3. Fewer patients treated with cyclosporine are transfused or A,B,DR matched compared with similar groups of noncyclosporine-treated patients. 4. Since the advent of cyclosporine, more kidneys have been used locally and, in addition, ischemia times are lower for cadaver kidneys. In addition, more diabetics are being transplanted with better results. 5. Cyclosporine does not seem to have an effect in living-related transplants that are one- or two-haplotype matched. There may possibly be deleterious effects associated with living-related transplants and the use of cyclosporine. 6. Patient survival since 1972 has increased one to two percentage points each year to the present time. This increase in patient survival is probably associated with those factors that strongly influence graft outcome (i.e., patient care, transfusions, matching, and immunosuppressive therapy).

HLA-DR associated immune responsiveness.

Abstract: 1. HLA-DR1-positive recipients were found to enjoy superior graft survival when compared with DR1-negative patients (72.5% versus 66.5%, p less than 0.00001) in kidneys transplanted since 1980. These patients had the highest graft survival rates in first cadaver, cadaver regraft, and living-related donor transplants. This was seen with patients regardless of the degree of DR-antigen matching. Within one day of the transplant, this advantage of DR1 patients was detectable when graft function was examined. 2. In white recipients, DR1-positive patients had the best graft survival rates. In black recipients, DR1-positive recipients also had the best graft survival rate; however, DR4-positive recipients also had very good graft survival. Whether or not these patients represent a unique population is unclear at this time. 3. In kidneys transplanted since 1983, DR1-positive patients again had the best graft survival rates. This was the case with and without the use of CsA for immunosuppression. DRw9-positive patients had the poorest graft survival rate (52%) in patients without CsA and the best survival rate (84%) of patients treated with CsA; however, because of the low number of patients, these survival rates were not significantly different from the average. 4. In the analysis of transplants performed since 1980, no association between the DRw6 antigen and low graft survival was noted. When the analysis was restricted to grafts transplanted since 1983, DRw6-positive recipients had the poorest graft survival rates. This was true both with and without the use of CsA. No beneficial effect of DRw6 in the kidney donor was seen regardless of the recipient's DR type.

Beneficial HLA matching in centers using cyclosporine A.

Abstract: In this chapter the linear model for the relationship between cumulative HLA mismatches and graft loss is shown to be invalid. HLA-A and -B mismatches and HLA-DR mismatches appear to differ in potency. A single mismatch at the HLA-DR locus is associated with a maximum risk of graft loss. These findings permit a simple division of transplants into beneficially matched (000, 100, and 010) and nonbeneficially matched (all other 23 combinations). In centers where more than two-thirds of patients were treated with CsA at three months, a similar dichotomy between beneficially and nonbeneficially matched transplants was observed, confirming the view that CsA-treated patients benefit from good HLA-A,B and DR matching. Organ-sharing schemes are designed to realize the full potential of matching and their potential can be investigated by simulation studies. These indicate that if all organs were unconditionally offered to a multicenter pool of more than 3,000 recipients, more than 60% of transplants could be beneficially matched.

The Los Angeles Transplant Society.

Abstract: For some 20 years a coordinated arrangement for sharing cadaver organs has been in place in Southern California. It's 11 transplant centers have performed 4,947 kidney transplants from 7,480 referred donors. There were 430 transplants done in 1985. The policy has been to keep one kidney and share the other within the pool. This has resulted in a better than average level of matching for HLA, and an overall better than average graft survival. The graft survival rates at the centers have been increasing yearly. Much of the improvement in graft survival resulted from the introduction of cyclosporine, but a summation of many factors contributed to a steady yearly increase. There are some 600 patients waiting for transplantation. With greater efforts in procurement of cadaver kidneys, especially from minorities, and continued collaboration between the transplant centers, it should become possible to transplant all those who are in need of a kidney.

Univariate and multivariate analyses of cadaver kidney graft survival data.

Abstract: 1. Clinical data on 6632 first cadaver transplants performed since January 1983 were analyzed by multivariate (Cox regression) and univariate (life-table) methods. 2. Cox regression analysis showed blood transfusion, recipient's race, HLA mismatch, highest antibody, warm ischemia time, and cyclosporine treatment as significant factors affecting graft survival. 3. A comparison of survival curves predicted by Cox regression analysis and that by the life-table method showed close agreement between the two methods. 4. Cyclosporine was one of the most significant variables affecting graft survival. There was a 13% overall increase in one-year graft survival due to cyclosporine treatment. However, other factors were still significant; they have not become obsolete in the cyclosporine era.

HLA matching for cadaver renal transplantation in SEOPF: the impact of cyclosporine. Southeastern Organ Procurement Foundation.

Abstract: Since the introduction of CsA in 1983, several changes in SEOPF activity have been observed: 1. Organ recovery has increased at a rate slower than candidate registration, whereas the utilization rate has increased substantially. 2. Overall organ sharing has decreased for both CsA and non-CsA-treated patients. 3. The percentage of poor HLA-A,B matched recipients has increased for both CsA- and non-CsA-treated patients. 4. The use of cold storage preservation has increased for both CsA- and non-CsA-treated patients. 5. The use of ALS has decreased, predominantly in CsA-treated patients. 6. A majority of diabetics are being treated with CsA. 7. There is substantial individual variation in SEOPF center preferences for CsA use, HLA matching, and use of shared kidneys. In terms of graft outcome, the following associations have been observed: 1. The incidence of delayed graft function has increased with shared kidneys only, suggesting sharing of poorer quality as well as fewer kidneys. 2. First transplant recipients receiving CsA tend to have lower delayed graft function rates, possibly as a result of treatment selection. However, the risk of graft failure associated with delayed function is greater in patients receiving CsA. 3. By univariate analysis, there is an additive benefit of HLA-A,B matching and CsA use in patients receiving local kidneys with immediate function. 4. By multivariate analysis, there is a significant relative risk of graft rejection associated with poor HLA-A,B matching in patients receiving CsA. 5. By multivariate analysis, there is an apparent risk of graft loss associated with shared organs, but only in patients receiving CsA. One possible explanation is that poorer quality kidneys are being accepted for patients treated with CsA. 6. By multivariate subset analysis, there is a significant benefit of CsA use in patients whose HLA is poorly matched, but no observed benefit in well-matched patients. 7. Definitive evaluation of the relative effects of CsA and HLA matching on cadaver renal allograft survival must await long-term follow-up data on survival and function, and the ability to control for center bias in sharing, HLA matching, and CsA use.