Risk rate and long-term kidney transplant survival.

The findings from the UNOS Scientific Renal Transplant Registry are summarized in the following table. We've also provided our opinions on ways to influence the risk factors in the Discussion section. [table: see text]

Advances in kidney transplantation: 1985-1995.

Graphs and tables published 10 years ago in our Clinical Kidney Transplants 1985 book are compared to current analyses. Impressive progress is apparent over the past decade. During this period, the effects of factors such as transfusion and the duration of first grafts on second grafts have disappeared, while the effects of factors such as cold ischemia time, regrafts and original disease have diminished in magnitude. Other factors, including HLA matching, donor age and race, continue to exhibit significant influence. It should be emphasized that most of these comparisons apply to one-year graft survival. Thus, our attention must now turn to factors which influence 10-year graft survival. Though 10 years is considered long-term survival to transplant physicians, for patients, it is but a brief period of life.

Cytomegalovirus antibody status and kidney transplantation.

1. First cadaver-donor recipients had a 7% death rate if the kidney originated from a CMV+ donor compared with 5% if the kidney came from a CMV-donor. This 2% difference was highly significant (p < 0.001). Graft survival rates were correspondingly 2-3% lower as a result of deaths. 2. This same trend was noted in the 1991-1993 period as in the 1988-1990 period. 3. Increased incidence of deaths in D+/R+ transplants was most frequently statistically significant when patients were divided by early function. 4. Death rates in diabetics rose from 7% in D-/R- combinations to 13% in D+/R- patients (p < 0.001). Patients with other diseases did not show as marked an effect. 5. Among kidneys from living-related donors, there was no noticeable effect of donor CMV status. Thus, for these donors, no precautions need be taken regarding CMV status. Spousal-donor transplants had a higher graft survival if a D-/R- rather than other combinations were used. 6. The incidence of CMV positivity was slightly higher in Black patients compared with Caucasians, in females compared with males, and increased progressively with age. CMV positivity increased in patients with multiple grafts, presumably because transplanted patients increased in CMV positivity. Among patients who were on dialysis, the CMV positivity was higher than in donors of cadaver organs. There was a substantial difference in CMV positivity in different areas of the country, ranging from 36% in Ohio to 65% in Washington. 7. The HLA matching effect was greater than the CMV effect, justifying its use as the main prospective factor in kidney allocation. CMV prophylaxis is needed for patients receiving kidneys from CMV+ donors. The data indicate that, whenever possible, CMV+ donor kidneys should not be used for CMV- IDDM patients.

Thirty-year trends in clinical kidney transplantation.

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.

Long-term kidney graft survival.

1. More than 90% of long-term grafts were first transplants. 2. The percentage of long-term transplants from living-related donors decreased from 78% in the years prior to 1968 to 42% in the 1973-1977 period. 3. More than 60% of living-related long-term grafts were from sibling donors. 4. Among long-term survivors, there was no difference from the expected rates in the percentage of red blood cell groups. 5. HLA-A,B matching resulted in significant improvement in graft survival rates for both cadaver donor and related transplants.

[Surgical enucleation for renal cell carcinoma. A case report].

We present a case of bilateral synchronous renal cell carcinoma treated with surgical enucleation. Urological consultation was asked to evaluate masses of the kidneys, which were detected during a diagnostic imaging on a 58-year-old man with hepatic disorder. Excretory urograms showed definite bilateral upper pole renal masses. Bilateral selective renal angiograms disclosed neovascularity in the small masses. Surgical enucleation of the left renal tumor by a flank approach was performed. The surgical specimen being 3.5 by 2.5 by 2 cm (29 g) was pseudoencapsulated and was identified renal cell carcinoma of the clear cell type, grade 1. INF alpha, pathologically. Seven weeks after, a pseudoencapsulated tumor of 3 by 2.5 by 2 cm (16 g) in the right upper pole was removed by simple enucleation. The pathological diagnosis was renal cell carcinoma of clear cell type, grade 2, INF alpha. The patient is well without evidence of recurrent or any residual disease at 21 months after the second operation. Renal function remains with in normal limits (CCr 110 ml/min). Of our collected cases of bilateral synchronous renal carcinomas treated by bilateral conservative surgery, clinical data are available for 11. Including our case, a total of 12 cases are reviewed.

Sex and age effects in renal transplantation.

1. Since 1985, 1-year graft survival in first cadaver transplants has remained constant at 78-80%. One-year graft survival rates for recipients over age 50 improved with CsA from 58% in 1981-82 to 78% in 1985-86. Survival in recipients under age 10 was 70% from 1985 to 1988, but improved to 75% in transplants performed in 1989-90. 2. The percentage of immunologic failures decreased from 75% in recipients aged 1-10 to 54% in recipients aged over 50. Thirty percent of males aged 1-10 had rejection episodes during the transplant hospitalization compared with 15% of males over age 50. These findings support earlier studies suggesting young recipients have a stronger immune response. 3. The incidence of nonimmunological failures increased from 10% in recipients under age 30 to more than 30% in patients over age 50. 4. There were no significant differences in graft outcome associated with the recipient's sex. 5. Kidneys from donors aged 1-10 or over 50 yielded poorer results than those from adult donors aged 11-50. This donor age effect was most notable in broadly sensitized, retransplanted, or HLA-B,DR-mismatched recipients. 6. Discharge serum creatinine (SCr) levels over 2.5 mg/dl were reported for more than 40% of recipients given kidneys from donors under age 5 or over age 50. When the discharge SCr was less than 2.5 mg/dl, 1-year survival was 90%, regardless of the donor age. 7. Trauma deaths accounted for 90% of kidneys from male donors aged 15-30 and 70% of comparable aged female donors. Cerebrovascular accidents were the cause of donor death for 43% and 68% of kidneys from male and female donors over 30, respectively.

UCLA and UNOS Registries. Overview.

The subjects of this study were transplant recipients entered in the UCLA Registry file since 1984 and in the UNOS Registry since 1987. [table: see text] 5. Based on the data above, we conclude that the near 20% loss rate in the first year can be roughly allocated as follows: death 3%, technical 3%, agonal kidney damage 6%, and histocompatibility differences 7%. 6. The quality of HLA typing was assessed by examining the frequencies of the various specificities reported for cadaver donors in 8 yearly periods from 1984 to 1991. The A and B loci specificities were remarkably constant. The DR specificities were still undergoing stabilization. 7. No urine output on the first day, which occurred in approximately 10% of the first cadaver-donor transplants, resulted in about a 20 percentage point lower graft survival rate at 1 year. 8. Anuria on the first day increased with cold ischemia time, donor age, cerebral vascular accident donors, and retransplant recipients. 9. Graft survival with anuria on the first day and: [table: see text] 10. When dialysis was required during the first week, there was an approximate 15 percentage point decrease in 1-year graft survival in 25% of the patients. 11. One rejection in the first hospitalization period resulted in 67% 1-year graft survival. More than 1 rejection led to 57% 1-year graft survival. 12. Serum creatinine at discharge was an accurate indicator of subsequent graft survival. Approximately a 7 percentage point drop in 1-year graft survival was noted with each unit of serum creatinine above 2.0 mg/dl.

Pediatric recipients and donors.

1. Pediatric recipients comprised 6% of first cadaver transplants, 9% of cadaver retransplants, and 4% of parent donor transplants reported to the UCLA Transplant Registry between January 1984 and December 1989. 2. Very young pediatric patients (aged 1-5) had consistently poorer 1-year graft survival than older pediatric or adult recipients. Graft survival was 65%, 46%, and 86% at 1 year for first cadaver, cadaver regrafts, and first parent donor transplants, respectively. The comparable ranges for recipients over 5 years old were 73-77%, 65%, and 88%. 3. The poor outcomes for very young pediatric recipients of first cadaver transplants were mitigated by using adult male donor kidneys (75% 1-year survival) and HLA-B,DR matching (75% 1-year graft survival with 0-1 B,DR mismatch). 4. One-year graft survival improved from 66-78% with pretransplant transfusions in 11 to 18-year-old first cadaver transplant recipients (p less than 0.05), whereas transfusions improved 1-year graft survival in adult recipients by only 3%. 5. Cadaver kidneys from donors aged 1-5 yielded the lowest 1-year graft survival rate in first transplants (68%) and in regrafts (46%), whereas those from donors aged 16-18 yielded the best results (81% in first transplants and 66% in regrafts). 6. The poorest graft survival rates for each recipient age group resulted with kidneys from very young donors (aged 1-5). The lowest survival rate (51%) resulted when kidneys from donors aged 1-5 were used for recipients aged 1-5. 7. Prolonged CITs in excess of 30 hours had an extremely adverse effect on kidneys from donors aged 1-5. Kidneys from donors aged 1-5 with less than 18 hours CIT yielded 75% 1-year first transplant survival, whereas only 57% of those with more than 30 hours CIT survived. 8. The overall poorer outcome for very young pediatric recipients was apparently due to the use of age-matched donors for this group. Over 40% of first transplant recipients aged 1-5 received cadaver kidneys from donors aged 1-5.

An association between acute retinal necrosis syndrome and HLA-DQw7 and phenotype Bw62, DR4.

Human leukocyte antigen (HLA) typing was performed on 27 white patients with acute retinal necrosis syndrome. Antigens for the HLA-A, -B, -C, -DR and -DQ loci were determined, and frequencies were compared with racially matched controls. There was a statistically significant increase in the frequency of HLA-DQw7 (11 of 20 [55%] of patients vs 294 of 1546 [19%] of controls, P = .0004, relative risk 5.20) that remained significant at the P = .05 level when the P value was multiplied by the number of antigens tested. The HLA phenotype Bw62, DR4 is also more frequent than in normal control populations (4 of 25 [16%] of patients vs 26 of 1023 [2.6%] of controls, relative risk 7.49). These results support an association between the acute retinal necrosis syndrome and certain HLA specificities and suggest a possible immunogenetic predisposition to the syndrome in some patients.

Long-term survival of kidney grafts.

1. In the long-term period, the half-life effectively measured loss rate. For HLA-identical sib donors the half-life was 25 years; for parental donors, 13 years; and for cadaver donors, 8 years (now possibly 11 years). 2. HLA-A,B,DR matching exerted the greatest effect on half-life, for a half-life of 17 years was achieved for cadaver donors. This rate was not quite as high as that for A,B,DR matched siblings but was higher than the one haplotype mismatched parental donor transplants. 3. Caucasian recipients had a half-life of 8 years compared to 5 years for black recipients. 4. Excellent centers had a 10-year half-life compared to 5 years for fair centers. 5. Cold ischemia time over 24 hours, recipient age over 55, and donor age of 50-60 had a small effect on the half-life in the order of 1 to 3 years. 6. Among the short-term factors that affect the 1-year graft survival, there was a 12% difference between excellent and fair centers. An 11% difference between A,B,DR matched transplants and 6 A,B,DR mismatched grafts was noted. First-cadaver donor grafts had a 10% higher graft survival at 1-year than second grafts. Other factors together with the difference in 1-year graft survival between the extremes were as follows: sensitization 9%, race 8%, transfusion 6%, donor age 6%, diabetic 3%, recipient age 3% and cold ischemia 1%. Thus more factors affect short-term survival than long-term survival.

The race effect.

1. One-year graft survival rates were 93% for recipients of HLA-identical sibling transplants in Blacks and Caucasians. One-year graft survival rates were lower in Blacks than Caucasians by 6% for parent donor, 8% for first cadaver, and 4% for cadaver donor retransplants between 1984 and 1989. 2. Although 1-year graft survival was consistently lower in Black recipients, there was no significant race difference when the recipient was over age 45 years. In transplants performed after 1986, there was no significant race difference when the recipient was over age 30 years. 3. Black recipients aged 15-30 years had the poorest 1-year graft survival at 64% each year between 1984 and 1988. One-year graft survival in comparable Caucasian recipients improved from 73-82% during this interval. The difference was greatest (18%) when comparing young Black and Caucasian males. 4. Caucasians had better early function than Blacks as judged from serum creatinine levels in the first 60 days. Fifty-two percent of Caucasians had excellent function (SCr less than 1.5 mg/dl) vs 37% of Blacks. Conversely, 22% of Blacks had SCr levels that never fell below 2.5 mg/dl vs 16% of Caucasians. There was no racial difference in early graft survival when transplants were stratified by function. The race effect became apparent after 6-12 months. 5. Long-term graft survival continues to differ dramatically between Black and Caucasian recipients. Transplant half-lives were consistently 4 years among Black and 7.5 years among Caucasian recipients of first cadaver transplants. Even comparing HLA-identical sibling transplants, the late loss rate in Blacks was double that in Caucasians. 6. The transplant center was an important factor in the race effect. Blacks transplanted at centers with overall high success rates had 79% 1-year graft survival, not significantly lower than that of Caucasian recipients. As the overall success rates declined at good and fair centers, the difference in 1-year graft survival between Black and Caucasian recipients increased from 8% to 12%. 7. The transplant center did not influence long-term graft survival in Black recipients. Transplant half-lives ranged from 4.9-3.9 years at excellent and fair centers, respectively. 8. The difference in graft survival between Caucasian and Black donors was primarily a center effect. In transplants to Caucasian recipients, there was no difference between Caucasian and Black donors at excellent and good centers, and a 16% difference at fair centers.

Overview and epitope matching.

1. Kidney graft survival rates have stabilized over the past 4 years, suggesting that gains achieved with CsA have plateaued. The overall 1-year graft survival is 77% for first cadaver donor transplants, 90% for parental donors, and 93% for HLA-identical sibling donors. Patient survival for all categories is now over 95%. 2. The UNOS 6-antigen match program has resulted in outstanding graft survivals. Of 88 kidneys which were transplanted into first graft recipients, the 6-antigen match kidney had a 1-year graft survival of 91% compared to 74% for the contralateral kidney transplanted locally (p less than 0.008). 3. In highly sensitized patients with more than 80% PRA the shipped 6-antigen matched kidney had a 91% 1-year graft survival rate compared to 72% survival in comparable control patients from the registry (p less than 0.005). In patients with less than 80% PRA, 6-antigen matched kidneys had 90% 1-year graft survival compared to 80% in controls (p less than 0.00001). 4. The spread of 1-year graft survival rates at 68 centers that performed more than 100 transplants was 63-94%. The cumulative graft survival of 6-antigen matches performed at 129 different centers was 90%. Thus, the strong center effect was neutralized by the use of matched transplants. 5. In contrast to the 1% of patients who would receive O-B,DR mismatched transplants on a random basis, if kidneys were shared in the national pool, 74% could receive such a transplant. We therefore propose that a keep one-share one policy be adopted for all kidneys harvested in the United States. If no 0-B,DR mismatched patient is available, both kidneys will be kept by the harvesting center. Since 63% of kidneys are currently being shared with other centers for various reasons, the 75% sharing suggested by the new system should not impose a hardship on transplant centers. The UNOS payback agreement will be replaced by this agreement by which shipping will be done only to achieve excellent matches. 6. In order to achieve a better method of excluding the worst mismatches, an attempt was made to develop a new method of mismatching using amino acid sequences of the HLA specificities. Donor and recipient types can be converted to amino acid sequences and the mismatching done on the basis of amino acids of mismatch at each residue or position. For each residue, specific combinations of amino acid substitutions were examined individually to determine their effect on graft survival. From these studies, a list of "immunogenic" amino acids was prepared, and graft survival was then computed for increasing numbers of amino acids of mismatch.(ABSTRACT TRUNCATED AT 400 WORDS)

Recipient and donor sex.

1. During the past 7 years, recipient sex had no apparent effect on transplant survival. 2. Recipients of female cadaver donor regrafts had an 8-12% lower graft survival rates at 1 year than recipients of male donor kidneys. Graft survival was poorer in both first and second transplants when the female donor was aged 31-50. 3. When graft function was delayed, 1-year graft survival was 6% lower for recipients of first transplants when the donor was female and 12% lower for retransplanted recipients of female donor grafts. 4. The striking effect of donor sex on regraft survival may be a transitory product of the "learning curve" for CsA. The difference between 1-year graft survival of male and female donor retransplants was 14% in 1984, 7% in 1985, and 5% in 1986.

Clinical transplants 1988. Overview.

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)

Kidney transplantation and donor-recipient ages.

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

[Comparative study on intravenous drip infusion of dibekacin once daily and twice daily in treatment of complicated urinary tract infections].

Dibekacin (DKB) was administered to patients with complicated urinary tract infections without any indwelling catheter to evaluate objectively and comparatively the efficacy, safety and usefulness of intravenous drip infusion once daily and twice daily in a well-controlled study. A 50 mg dose of DKB was administered twice a day to group A, and a 100 mg dose was given once a day to group B. In both groups the drug was given by 1-hr i.v. infusion for 5 consecutive days. Drug efficacy was evaluated in 72 (group A: 36, group B: 36) of the 83 patients treated, and the safety was evaluated on 81 patients (group A: 41, group B: 40). There were no significant differences in the background characteristics between the two groups. The overall clinical efficacy judged by the Committee for Evaluation of Clinical Efficacy was "excellent" in 14% and "moderate" in 50% of group A, and "excellent" in 17% and "moderate" in 64% of group B, the efficacy being higher for group B than group A, but the difference was not statistically significant. The overall drug efficacy rate for each type of infection excluding group 2, was slightly higher in group B, but this difference was not significant either. The overall clinical efficacy for each site of infection, was higher for group B but the differences were not significant. The overall clinical efficacy as judged by the attending physicians was "excellent" in 17% and "moderate" in 58% of group A, and "excellent" in 25% and "moderate" in 61% of group B. The intergroup difference was thus smaller than that judged by the Committee. The elimination rates against bacteriuria were 58% for both groups A and B, and the decrease rates including "cleared" were 42% against pyuria for both groups A and B. Bacteriological evaluation, showed that there was no significant difference in the eradication rates, between group A (65%) and group B (70%). But the eradication rate for gram-positive bacteria was 40% in group A and 81% in group B, there being a significant difference (P less than 0.05) between them. The evaluation of usefulness gave 44% and 53% "satisfactory" rates, respectively, for groups A and B. The results for the "average score" were also the same in both groups. There were no side effects in any of the 81 patients examined. Abnormal laboratory test values attributed to the drug were seen only in 3 and 2 patients in groups A and B, respectively, there being no difference between the groups.(ABSTRACT TRUNCATED AT 400 WORDS)

[Double-blind comparative clinical study of cefpiramide (SM-1652) and cefsulodin on complicated urinary tract infections due to P. aeruginosa].

The therapeutic efficacy and safety of Cefpiramide (CPM, SM-1652) at a 2 g/day dose were objectively compared with those of Cefsulodin (CFS) at a 2 g/day dose in patients with chronic complicated urinary tract infections (UTI) by P. aeruginosa in a double-blind study at 46 institutions in Japan. The results are as follows: The therapeutic efficacy was analyzed in 254 patients (136 cases administered CPM and 118 cases administered CFS) after excluding 20 cases as drop-out. Among 254 cases, the number of patients with infection of P. aeruginosa was 190 cases (100 cases administered CPM and 90 cases administered CFS), while that with infection of organisms other than P. aeruginosa was 64 cases (36 cases administered CPM and 28 cases administered CFS). By the administration of a 2 g/day dose for 5 days, the overall clinical effective rate of CPM was significantly higher than that of CFS in total patients. When the patients were classified into 2 groups with respect to causative organisms (P. aeruginosa and others), the clinical effective rate of CPM in patients with infections of P. aeruginosa was significantly higher than that of CFS, while the clinical effective rate of CPM in patients with infection of other organisms than P. aeruginosa was the same as that of CFS. As to the bacteriological effect on bacteriuria, the eradication rate of CPM was significantly higher than that of CFS not only against all causative organisms but also against P. aeruginosa. The rate of replacement by S. faecalis was significantly higher in the CFS-treated group than in the CPM-treated group. The same result was obtained on the rate of replacement by other organisms. The MIC values of CPM for isolated organisms before drug administration were lower than those of CFS. The incidence rates of side effects and the abnormal findings of clinical laboratory tests were the same for the CPM- and CFS-treated groups. From the results, it was concluded that CPM is a useful drug for the treatment of patients with chronic complicated urinary tract infections caused by P. aeruginosa.