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Based on analyses of the UNOS Registry data for cadaver kidney transplants performed between 1991-1999 we showed that: 1. 15-40 year old donor kidneys provided the best one-year graft survival rates. When donors were analyzed with recipients, younger (0-10) and older (70-90) donors and recipients (Table 2) had the lowest one-year graft success rates. 2. Chronic loss rate, the constant rate of graft loss between one and 5 years, showed younger donor kidneys had a significantly lower chronic loss rate compared with each older donor category. Apparently the younger donor kidneys have a resiliency and nephron reserve that provides better long-term function. However, they may have lower short-term (1-yr) graft survival rates, possibly due to their small size. 3. Black and White donor kidneys had similar one-year graft survival rates; however, in every age group, recipients of White donor kidneys had significantly better 5-year graft survival rates than Black donor kidneys. There was also a noticeably lower chronic loss rate among recipients of White than Black donor kidneys. 4. HLA-matched White donor kidneys had better one- and 5-year graft survival rates and lower chronic loss rates than HLA-mismatched kidneys. The matching effect was lost when the donor age increased beyond age 40. PRA had an effect both at one and 5 years after transplantation. The chronic loss rate was similar with high and low PRA. Therefore, PRA had a relatively short-term effect. 5. Cold ischemia time had a modest effect after 35 hours both at one and 5 years. However, the chronic loss rate was unaffected by CIT, suggesting prolonged ischemia time had a relatively short-term effect. 6. More focused attention on sensitization and lowered CIT can both have a significant effect on short-term graft survival rates. However, both matching and younger donor organs provide the best opportunity for better long-term graft success rates.

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.

1. Approximately 15% of males were sensitized by transfusions before their first grafts. About 40% of females were sensitized by pregnancies and transfusions. Following graft rejection about 60% of males and females were sensitized. 2. The one-year graft survival of nonsensitized and sensitized patients differed by 4 to 7% in first, second, and third transplants. The difference developed very early and even on the first day after transplantation. 3. Patients with a high peak level of antibody tended to have lower graft survival, particularly in regrafted patients. If the peak level of antibody was under 50% panel reactive antibody, graft survival was the same as in patients who never had preformed cytotoxins. 4. Parous women without transfusions and no preformed antibodies had a 49% one-year graft survival with no transfusions and 71% with transfusions. Similar findings were noted in regrafted parous women and those with preformed antibodies. Thus, pregnancy exerted a deleterious effect which was reversed by transfusions. 5. Between the best and worst HLA-A,B,DR match there was a 19% difference in one-year graft survival for nonsensitized patients, and a 26% difference in patients sensitized to more than 50% of the panel. A similar difference was noted in regrafted patients for sensitized and highly sensitized patients. 6. Transfusions had a greater effect on the outcome of transplantation than the state of sensitization. First cadaver donor patients without transfusions and without antibodies had a one-year graft survival of 57% whereas patients with more than 50% panel reactive antibodies had graft survival of 59 to 71%.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

1. Overall, positive FCXM reactions were associated with graft losses in regrafts but not in primary transplants. 2. In transplants involving older female or CVA donors, a positive FCXM appeared to be deleterious in both first transplants and regrafts. If the donor were a younger male and not a CVA victim, only FCXM positive regrafts had low graft survival rates. 3. We presented a 3-color technique allowing the differentiation of antibody reactions against T cells, B cells, and monocytes. Another method allows the simultaneous evaluation of both IgG and IgM reactions against T cells. Using these kinds of methods may make better identification of antibodies that may be harmful to a transplant allograft possible.

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.

1. The 3-month actual graft survival of 6-antigen matched transplants in the UNOS program was 96% compared to 85% in control kidneys which were not shipped (p = 0.004). Actuarial graft survival at 1 year was 89% for the 6-antigen matched kidneys and 78% for the controls (p = 0.02). 2. Several individual centers reported 1-year graft survival rates of 85-95% (in the first half of this volume). Various immunosuppressive protocols and attention to patient care resulted in high 10-year survival of 53% in 1 instance (Leuven). 3. The 1-year graft survival peaked at about 77% for transplants performed in 1985, 1986, and 1987. 4. Among transplants performed since 1984, HLA matching of cadaver donor transplants showed a 13% difference at 1 year between the best and worst A,B,DR matches, which expanded in 3 years to an 18% difference. 5. The center effect, which produces about a 13% difference in 1-year graft survival for cadaver donors, decreased to 0 in HLA-identical transplants. Thus, when the donor and recipient were histocompatible, all centers were able to achieve superior results. The results of the 6-antigen Match Study appear to validate this conclusion. 6. Preformed antibody is associated with a 9% decrease in graft survival for greater than 50% PRA in first grafts and 4% in second grafts. For peak antibodies, the difference was 7% for first grafts and 11% for second grafts. 7. Platelet flow cytometry in 23 patients with a positive flow cytometry crossmatch to T cells furnished a further refinement in grouping the patients. All 11 patients with a negative platelet crossmatch had functioning grafts at 1 month whereas only 5 of 12 patients with a positive platelet crossmatch had a functional graft at 1 month (p = 0.003). 8. The duration of first graft effect on the second graft has diminished considerably as immunosuppression improved. Patients whose first graft survived more than a year and who had a high 1-year graft survival of the second graft lost their second graft at an accelerated rate after the first year. At the end of 4 years, their survival was the same as that of the responder patients who had rejected their first grafts within 3 months. 9. False positive crossmatches, especially in "highly" sensitized patients were identified by the use of DTT. Transplants into 69 patients who were positive by the standard test but negative after DTT had a 94% 1-month function rate.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

1. Hyperacute rejections occurred in 0.6% of 19,415 first cadaver donor grafts and 1.9% of 4,326 regrafts. When grouped into those without preformed cytotoxins, 0.5% first grafts and 1.3% of regrafts had hyperacute rejection. Among patients with cytotoxins 1.3% of first grafts and 2.6% 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)

1. One-year patient survival rates improved markedly year by year for regrafted kidney patients reaching 93% in 1986, as compared with 96% in first grafts. 2. The graft survival rate of regrafts also showed steady improvement, but was not benefited by the introduction of CsA as much as in first grafts. One-year graft survival rate was 63% for regrafts in 1986. 3. The functional graft survival was higher with advancing recipient age in first grafts, but remained essentially constant regardless of age in regrafts. We interpret this to mean that older patients have depressed immunologic capability to reject first grafts, but those immunized patients by rejecting a first graft have undiminished reactivity. 4. A high graft survival rate of 68% at one-year was observed for patients who had been sensitized before their first transplant but lost their antibodies before the second transplant. One-year graft survival of those who were not sensitized before both first and second grafts was 60%. 5. The duration of first grafts significantly influences the outcome of second grafts (p less than 0.00001). The highest graft survival was obtained in recipients who had functioning first grafts for more than 2 years (69% at one year), followed by those for recipients whose grafts had functioned for one to 2 years, 6-12 months, and 3-6 months. Patients who lost their first grafts within 3 months had the lowest graft survival rate (44% at one year). 6. The time interval had an influence on the outcome of second grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Eight hundred and sixty kidney transplants were performed at the University of Pittsburgh over a 3.75-year period between January 1, 1986 and October 19, 1989. Recipient selection was by means of a computerized point system designed to allocate organs equitably. Ninety-three percent 1-year patient survival and 74% 1-year graft survival were obtained in the overall group; 80% 1-year graft survival was obtained in patients receiving immunosuppression with CsA, azathioprine, and prednisone. These data serve as a measure of what can be achieved with an equitably based allocation system and can serve as a basis of comparison with other allocation protocols or new immunosuppressive regimens.

1. In 9 yearly cohorts from 1978 to 1986, male and female recipients had the same one-year graft survival rates for first cadaver donor grafts. For regrafts, female recipients had superior survival in 2 out of the 9 years. 2. In contrast, in the same 9 yearly cohorts, female donor first cadaver grafts had a lower survival than male donors in 8 out of the 9 comparisons, although the difference was not statistically significant. For regrafts for the last 5 years, in 4 different years females had a statistically significant lower graft survival rate compared to males. 3. The lower survival rate of female donor kidneys was especially evident in the CsA-treated regrafted patients, although a similar tendency was noted also in non-CsA-treated regraft patients. 4. Grafts from females older than 30 years had the lower survival rate in the regrafted patients. 5. The depressed survival effect of female donor kidneys was not affected by the recipient's sex or original disease. 6. Female donors kidneys from either trauma or nontrauma donors yielded lower survival rates. Thus, the cause of death in the donor is probably not the principal explanation for the donor sex effect. Since males more often die from trauma, it was initially thought that the sex effect could be attributed to the difference in mode of death of the donor. 7. Regrafts from living-related female donors who differ by one HLA haplotype had a lower regraft survival rate than grafts from male donors. 8. It is unlikely that a sex-associated histocompatibility antigen exists in the clinical kidney transplant situation since females who received 2 grafts from male donors had a statistically significant superior survival to females who received 2 successive grafts from female donors. Thus, rejection of a male graft by a female does not sensitize the recipient to a second male graft, and second female grafts when the first was a female result in a lower graft survival. 9. Poor mismatches for HLA-A, B, or DR antigens were more deleterious with female donors than male donors. With CsA, the lower regraft survival with female donors was statistically significant in all categories of DR mismatches. 10. Transfusions did not influence the donor sex effect. The level of panel reactive antibody also did not affect the lower survival of female donor kidneys. 11. The donor sex effect was apparent in first grafts and regrafts even one month after transplantation.

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)

1. There was a "transfusion effect" for cadaver kidney transplant recipients and the improvement of 1-year graft survival with transfusions was 7.1% (p0.0002) in 1987. 2. Two or 3 pretransplant transfusions are sufficient to obtain the maximum transfusion effect. 3. In 1988, about a quarter of the patients received first cadaver kidney transplants without any pretransplant transfusions, whereas only 10% were nontransfused during the period between 1981 and 1984. 4. The transfusion effect diminished as patients aged. The increase in 1-year graft survival with transfusions was 17% in patients aged 16-25, 4% in patients aged 46-55, and 1% in patients over 55. 5. Both transfused and nontransfused patients had as high as 83% 1-year graft survival rates when they received 0 A, B, DR-mismatched kidneys. Transfusions improved graft survival by as much as 8% for recipients with mismatched grafts. 6. There was no transfusion effect in recipients of 0 DR-mismatched kidney transplants. Transfusions improved the 1-year graft survival rate by 8-10% for transplant recipients with 1 or 2 DR-mismatched kidneys. 7. The transfusion effect was greater in black (8%) than white (4%) recipients; however, the 77% 1-year graft survival rate for transfused black recipients of 0 DR-mismatched kidneys did not differ from that of transfused whites. 8. Considering the transfusion effect on graft failure rather than graft survival, the failure rate in nontransfused patients could have been reduced by 30% in transplants performed between 1976 and 1979, 17% in transplants from 1980 through 1983, and 21% in transplants since 1984 with blood transfusions.

1. Cyclosporine treatment did not increase nonfunction for one month, delayed function, or first-day nonfunction in comparison with noncyclosporine-treated patients. Despite almost equivalent initial poor function rates, cyclosporine-treated patients had a higher one-year graft survival rate than noncyclosporine-treated patients. Thus, unlike many other factors, cyclosporine did not have its main effect during first-month function. 2. In regrafts there was a higher incidence of one-month and one-day nonfunction. However, these poor-function categories were not significantly increased in cyclosporine-treated patients. 3. Warm ischemia longer than 10 minutes increased the rate of first-day nonfunction and delayed function. 4. Cold ischemia longer than 36 hours increased the rate of first-day nonfunction, delayed function, and one-month nonfunction. Cyclosporine-treated patients with 36 to 48 hours cold ischemia had a one-year graft survival rate of 76% compared with 68% for those with kidneys preserved longer than 48 hours. 5. One-year graft survival rates were similar for machine- and cold-preserved kidneys if cyclosporine was used, although machine preservation led to slightly less early poor function. 6. Cyclosporine had a beneficial effect for first grafts and regrafts preserved by cold storage. However, it had an adverse effect in machine-preserved kidneys for regrafts. 7. In cyclosporine-treated patients, kidneys with delayed function had a higher (3% at one year) survival rate than those with immediate function. This was reversed in noncyclosporine-treated patients where immediate-function kidneys had a 6% higher one-year graft survival rate than those with delayed function. The same relationships held for regrafts. 8. Cyclosporine improved the one-year graft survival of delayed-function grafts by 21% in first grafts and 12% in regrafts. For kidneys which immediately functioned, cyclosporine therapy increased the one-year graft survival rate by 11% for first grafts and 3% for regrafts. Thus, cyclosporine appears to have a greater influence on kidneys with delayed function than on those with immediate function. 9. The incidence of kidneys that did not function for one month was higher (15%) in regraft patients than in first graft patients (8%). The frequency of delayed function was approximately the same for regrafts and first grafts. Thus, the main difference between first and regrafted patients occurs in the higher incidence of kidneys that never functioned among regrafted patients.