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1. LifeLink Foundation, a not-for-profit organization, has been the driving force and absolutely essential entity for kidney and liver transplantation in Tampa providing all the components (patient, organs and clinicians) save for inpatient hospitalization. It also plays a big role in the heart transplant program. LifeLink has increased the kidney transplant rate from the first 1,000 done in 17 years to the second 1,000 in 7 years and is on a pace for the third 1,000 in 5 1/2 years. 2. Because of its innovative programs, cadaver donor procurement by the Tampa LifeLink OPO has been roughly double the national average for the past 10 years. Because of cadaver kidney availability the median wait time from activation on the wait list to transplantation over the past 5 years was 159 days. The recent transplant rate is 14.7-22.7% higher than the national average, dependent upon the parameter measured. Similar results are seen for Tampa patients awaiting heart and liver transplantation. 3. The overall outcome of 1,184 cadaver kidney transplants performed in the decade 1989-98 was similar to that reported from the UNOS database in this series of publications. a) One- and 2-year graft survival increased 2% per year over the decade with a recent one-year graft survival rate of 96%. The overall T1/2 was 10 years. b) Our disastrous 1994 results were quickly reversed by a more intense pretransplant medical evaluation, the introduction of mycophenolate mofetil, more aggressive and earlier treatment of rejection episodes, and mandatory T- and B-cell flow cytometry crossmatching for all transplants. The incidence of rejection episodes decreased from 40 to 20%, and the first year immunological graft loss decreased from 5%, to 1.9%, to 0.8%, to 1.4% and 0% over the succeeding 4 years. 4. Individual factors affecting allograft survival were strikingly similar to national data, although all did not react statistical significance probably due to the smaller numbers. a) Primary and second grafts had similar survival rates (p = 0.97) whereas the third or subsequent graft survival was 7-32% poorer (p = 0.02). b) Black recipients had survival rates 10-13% lower than Caucasians and other races (p = 0.003). c) Patients with a peak PRA > 50 had survival values 4-13% poorer than those with < 50 PRA (p = 0.14). d) Patients with 2-4 HLA mismatches had graft survival rates 4-10% poorer than those with 0-1 mismatch (p = 0.12), whereas those with 5-6 mismatches had rates 6-17% poorer (p = 0.04). e) Although 22% of our transplants were to patients > 60 years of age, there was no difference (p = 0.81 to 0.90) in graft survival for the age groups 0-40, 41-60 and > 61. However, the proportion of grafts lost due to patient death compared with all allografts lost, was very different at 21% in the youngest group, 43% in those 41-60 years of age, and 63% in recipients > 61 years. 5. The rate of delayed graft function with imported kidneys was higher (27 vs. 16%, p = 0.006) but essentially the same as local kidneys with the same ischemia times. However, 41% of local kidneys were transplanted within 12 hours of procurement. Totally, 78% of local kidneys were transplanted within 18 hours (11% DGF rate) versus 79% of imports being transplanted at > 18 hours (32% DGF rate). Ischemia time, not the kidney source is the key issue since: a) There was no difference in overall graft survival of imported versus local kidneys (p = 0.95) nor in comparing local versus import kidneys with (p = 0.66) or without (p = 0.69) DGF. b) There was, however, a 11-17% overall poorer graft survival over 3 years in kidneys with DGF (p < 0.001) seen with both local (9-18% poorer, p = 0.0002) and imported (12-19% poorer, p = 0.008) kidneys. c) Kidneys displaying DGF came from older donors (40 vs. 34 years, p = 0.023) and had longer ischemia times (21 vs. 15 hours, p < 0.0005). 6. Dual kidney transplants were started in late 1996 with older or marginal donors to provide a better chance of success fo
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PMID:The LifeLink Foundation and cadaver kidney transplantation in Tampa. 1103 33

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.
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PMID:The influence of donor age on kidney graft survival in the 1990s. 1103 52

Given the constant flux in caseload and the number of personnel available in the OR, waiting for a final XM often prolongs organ preservation time (a room available at the time a XM is started is not available when the XM is completed). Longer preservation is associated with increased DGF and decreased graft survival. We have shown in a retrospective analysis that final XMs on 0% PRA recipients were always negative (Transplantation, 1999). We now describe a policy of: a) not doing screening XM and b) proceeding to the OR without a XM, in situations where the recipients's PRA has been documented to be 0% and when there have not been any interim transfusions (and the OR is ready before XM completion). Final XM is completed after the transplant. All patients send sera every 6 weeks for PRA (antiglobulin technique). If > o r=3 consecutive PRAs are 0%, no donor-specific screening XM is done prior to calling the patient in for tx (UNOS allocation algorithm used). If there have not been any interim transfusions, we have proceeded to tx prior to completion of the final XM. Between 1/1/98-12/31/99, we did 109 CAD kidney (K) and 79 simultaneous kidney pancreas (SPK) tx; 67 (61%) K and 56 (71%) SPK had 0% PRA. Of the 0% PRA, 25/67 (37%) K and 28/56 (50%) SPK had no pre-tx XM. For K with no XM, cold ischemia was shorter (13.2+/-0.2 vs. 18+/-0.9 hrs, p=0.01) and DGF less (12% vs. 24%, p=0.3); for SPK with no XM, cold ischemia was shorter (15.2+/-2 vs. 18+/-0.9 hrs, p=0.1); no diff in DGF. All post-XM were negative and there were no hyperacute rejections; there was no diff in acute rejection episodes. Actuarial 1 yr graft survival: no XM-K=87.5%, SKP=82%; Yes XM-K=88%, SKP=86% (NS). Our data suggests it is safe, in select circumstances, to proceed to the OR without a XM. Elimination of the screening XM for 0% PRA candidates saves money. Proceeding of the OR (if available) without a final XM shortens cold ischemia time.
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PMID:Kidney and pancreas transplantation without a crossmatch in select circumstances--it can be done. 1168 16

1. Although the number of cadaver donor transplants did not increase substantially over the past 10 years, unrelated living donor grafts increased from 153 in 1991 to 1,661 through 2000. Use of spousal and other unrelated donor organs contributed to this increase. There was a modest increase in living-related donor transplants from 2,328 in 1991 to 3,451 in 2000. 2. Cadaver donor graft survival at one year improved from 84% in 1991 to 90% in 2000. In contrast, one-year graft survival of living donor transplants only improved from 93% in 1991 to 95% in 2000. 3. Throughout the 10-year period, approximately 13% of transplants were repeat transplants from cadaver donors and roughly 8% were regrafts from live donors. 4. Cadaver donor transplants into White recipients declined from 68% in 1991 to 60% in 2000. For living donors, the percentage of White patients remained constant at about 70%. 5. Graft survival in patients of all races was about equal at one year but diverged at 3 years, with Asians having the highest and Blacks having the lowest 3-year graft survival rates. 6. Average donor age increased from 31.7 in 1991 to 36 in 2000 for cadaveric donor transplants and 37.9 in 1991 to 40.4 in 2000 for living donor transplants. Cadaveric kidneys from donors older than 50 years of age yielded significantly lower 3-year graft survival. 7. Average recipient age for cadaveric donor transplants increased from 42.1 in 1991 to 46.8 in 2000. The average recipient age for living donor transplants also increased steadily from 33.7 in 1991 to 42.9 in 2000. There was relatively little effect on graft survival rates for advanced age recipients. 8. The percentage of sensitized recipients receiving cadaver donor grafts declined from 27% in 1991 to 21% in 2000. Similarly, sensitized recipients receiving living donor grafts decreased from 17% in 1991 to 13% in 2000. Graft survival in patients with more than 50% PRA was lower at 3 years for patients receiving cadaveric donor grafts. Highly sensitized patients receiving living donor grafts had graft survival rates similar to those who were not sensitized. 9. Cold ischemia times decreased from an average of 24.2 hours in 1991 to 18.9 hours in 2000. Improved graft survival rates over those 10 years were noted in all groups, and even cold ischemia times more than 36 hours yielded 3-year graft survivals comparable to those with lower cold ischemia times in 1998. 10. The need for dialysis has remained constant at about 23% over the last 10 years for patients receiving kidneys from cadaveric donors. The rate of dialysis for patients receiving kidneys from living donors was about 5% for each of the 10 years examined. First day anuria increased from 11% in 1991 to 16% in 2000 for cadaver donor transplants and 3% in 1999 to 5% in 2000 for living donor grafts. 11. Cadaveric donor patients requiring dialysis had a 3-year graft survival rate of 63% if there was no first day anuria and 56% if they had first day anuria. This is in contrast to 80% 3-year graft survival for those with immediate diuresis and no need for dialysis. The 3-year graft survival rate for those receiving living donor grafts and needing dialysis was 58% if they had first day diuresis and 41% if they ware anuric on the first day. Conversely, those who had first day function and did not require dialysis had 89% 3-year graft survival. 12. Among the patients receiving cadaveric grafts with first day diuresis there was a marked reduction in those with rejection, from 21% in 1991 to 5% in 2000. Similarly, for this type of patient receiving living donor grafts, the reduction was 17% in 1991 to 5% in 2000. However, graft survival among these patients did not change significantly. The greatest improvement was noted in those with first day anuria and no rejection. 13. Patients who did not require dialysis, and had rejection prior to discharge decreased markedly from 17% in 1991 to 3% in 2000 in those receiving cadaveric grafts and 15% in 1991 to 3.9% in 2000 for those receiving living donors. Graft survival of cadaveric transplants in those needing dialysis, with and without rejection, improved the most in the 10 year period. 14. Hospitalization days for cadaveric transplant recipients were reduced from 19 days in 1991 to 10 days in 2000 and 16 days in 1991 to 8 days in 2000 for recipients of living donor grafts. There was an increase in discharge serum creatinine values from 2.3 mg/dl in 1991 to 3.3 mg/dl in 2000 for cadaver donor grafts. 15. Double therapy was utilized for about 15% of cadaveric and living donors. There was a sharp increase in induction therapy, peaking at 51% in 1994 and decreasing to 5% by 2000 for cadaveric donor transplants. Induction did not improve graft survival for either cadaver or living donor transplant recipients. 16. Triple therapy improved graft survival of White and Black patients, but did not affect the half-lives in either race. 17. The lower graft survival from older donors was not affected by triple therapy for cadaver donor transplants. Triple therapy removed the donor age effect for recipients of living donor grafts. 18. Triple therapy practically eliminated the effect of sensitization for cadaveric donor grafts. Both double and triple therapy virtually eliminated the sensitization effect for living donors. 19. Triple therapy significantly improved the survival of kidneys with more than 36 hours cold ischemia time so that 3-year graft survival was 76% at 3 years compared with 81% for kidneys stored 1-12 hours. 20. Triple therapy improved the 3-year graft survival of kidneys with first day anuria from 50% for double therapy to 69% for triple therapy in cadaver donor transplants. For living donor transplants, there was a similar improvement from 57% with double therapy to 72% with triple therapy. 21. Triple therapy improved the 3-year cadaveric graft survival rate of kidneys requiring dialysis from 51% with double therapy to 67% for triple therapy. There was a similar improvement for living donors needing dialysis from 37% to 61% at 3 years.
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PMID:Annual trends and triple therapy--1991-2000. 1221 88

Seronegative transplant recipients are at a high risk of developing primary cytomegalovirus (CMV) infection. The D+/R--constellation produces a 60%-80% probability of CMV disease. In such cases CMV prophylaxis is justified. Presentation of a 12-year old boy who developed a primary CMV infection following A combined liver-kidney transplantation; evaluation of prophylactic options and review of some difficulties in the diagnosis of CMV infection. A cadaveric liver-kidney transplantation (Tx) was done in a 12-year old boy with ESRD due to type I primary hyperoxaluria. CMV status: D+, R-; number of mismatches: 5. PRA 0; kidney cold ischemia time (CIT): 13.54 h; liver CIT: 10.10 h; immediate diuresis; Immunosuppression protocol: anti IL-2 receptor antibodies, steroids, mycophenolate mofetil (MMF); cyclosporine introduced on day 6. Over the first week, daily hemodialyses were done in order to remove oxalate deposits. Kidney and liver biopsies: no ACR, no oxalate deposits. CMV prophylaxis with ganciclovir started on day 0. Routine serology and PCR for CMV follow-up showed: pp 65, IgM and IgG, CMV. DNA (Murex CMV. DNA Hybrid Capture test 2.0): negative over the first 3 months. Day 98: CMV pp 65 positive, IgM neg, DNA neg. Day 108: pp 65 neg, IgM positive, IgG neg. CMV. DNA positive (15 x 105 copies/ml). Clinical status: except for mild Cushing, liver tests and kidney function were normal. Ganciclovir was administered intravenously (i.v.) and after 14 days continued perorally. A few days later, leukopenia with severe neutropenia (neutrophil count: 400) and right otitis media developed. MMF and ganciclovir were withdrawn for a few days and reintroduced after WBC count reconstitution. We had no possibility to monitor MMF. Day 150 pp 65 neg, IgM still positive, IgG neg. No clinical signs of infection. Liver and kidney functions normal. After liver-kidney transplantation in a CMV high-risk pediatric patient (D+/R-), asymptomatic CMV primary infection developed. Although ganciclovir prophylaxis could not prevent the infection, it was mild and delayed. Due to bone marrow suppression, discontinuation of MMF and ganciclovir was necessary. Antigenemia assay pp 65 did not correlate very well with CMV viremia so it could not be recommended as a routine test. It should be used in combination with other CMV tests.
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PMID:[Primary cytomegalovirus infection after combined cadaveric transplantation of the liver and kidney]. 1287 72

1. GENERAL: We updated prior analyses of renal retransplants reported to the UNOS Registry by estimating the compound effects of 22 covariates on regraft survival within 2 consecutive posttransplant risk periods. During an early risk period, 9,126 kidney-only regraft recipients were followed through one year, and, in a second risk period, 7,798 recipients whose regrafts survived beyond one year were followed for 5 years posttransplant. The study sample represented a unique set of patients whose first renal transplants were also recorded by the registry. 2. RELATIVE INFLUENCE OF TRANSPLANT FACTORS AND CENTER: From a multivariate log-linear analysis, the top 5 factors influencing one-year regraft survival rates were ranked as follows: 1) transplant center (accounted for 24% of the variation in short-term outcomes); 2) duration of first graft (19%); 3) donor age (15%); 4) recipient's body mass index (7%); and 5) year of transplant (6%). Ranking long-term outcomes demonstrated that donor age was the dominant factor governing the 5-year survival rates among regrafts, accounting for 30% of long-term variation. Transplant center, recipient age and race, and donor relationship accounted for another 16%, 14%, 10% and 8% of changes in long-term regraft survival, respectively. Despite center effects, a center's volume did not appear to be associated with outcome, and a center's short-term effect did not predict its long-term results, as the correlation between one- and 5-year center-specific rates was small (R = 0.11) and statistically insignificant (P = 0.15). 3. RECIPIENT FACTORS RELATED TO FIRST TRANSPLANT: Among 4 recipient factors related to a first transplant, only the first graft's survival duration significantly influenced both short- and long-term outcomes of regrafts. If the first graft survived for more than 2 years, a regraft had an approximate 90% chance of surviving to one year as compared with an 80% chance if the first graft failed within 2 years. Regrafts among recipients whose first graft lasted more than 4 3/4 years exhibited better 5-year survival rates (82.2%) versus the less-than-average rates for the other groups. 4. RECIPIENT FACTORS: Six of the 7 recipient factors selected for analysis significantly influenced short- or long-term regraft outcomes: 1) female recipients had significantly higher long-term regraft survival rates; 2) Black recipients of regrafts had poor long-term results; 3) children (0-12 yr) exhibited markedly diminished one-year regraft survival rates, and teenage recipients exhibited poor long-term regraft function; 4) obese recipients (body mass index > 30 kg/m2) had poor one-year and 5-year regraft survival rates; 5) impaired functional status immediately pre-retransplant significantly reduced both short- and long-term rates; and 6) regraft recipients whose PRA was above 0% exhibited diminished one-year and 5-year regraft survival rates. 5. DONOR FACTORS: Regraft recipients receiving a living donor's kidney had 87% one-year graft survival, outperforming cadaveric regrafts by 8 percentage points during the initial period. At 5 years, survival rates for patients receiving living related (except parents) or unrelated donor regrafts enjoyed above average 5-year survival rates, but parental and cadaver types of donors demonstrated poor long-term values. The strong short-term effect of donor age emanated from poorer regraft functions from both younger and older donors, whereas the long-term effect arose primarily as a result of the poor regraft functions from older donors. After 24 hours of cold ischemia time, early cadaveric regraft survival rates were significantly impaired. 6. TRANSPLANT FACTORS: This study clarified the effects of HLA mismatches and re-exposure to mismatched antigens on regraft survival rates. Generally, receiving a zero mismatched regraft was beneficial. Specifically, class I incompatible regrafts with repeat AB mismatches demonstrated superior long-term rates, even surpassing the 5-year results for 0 AB mismatches. Incompatible class II regrafts with re-exposure to DR antigens had marginal reductions in short- and long-term outcomes. Increasing numbers of HLA-AB mismatches did not seriously impact regraft survival, but any DR mismatch seriously reduced the one-year regraft survival rate.
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PMID:A multi-factor analysis of kidney regraft outcomes. 1297 60

Kidney transplantation has become therapy of choice for patients with end-stage renal failure. However, many factors may cause graft rejection or delayed graft function, both of which decrease the prognosis for graft survival. For transplantologists the most important endeavor is to eliminate factors responsible for shortening graft function and to find those predictive of immediate graft function. The aim of the study was to investigate which factors influence early graft function. We retrospectively reviewed 442 renal transplant patients performed between 1990 and 1995 in two Szezecin units. All patients received an identical immunosuppressive drug schedule. Three hundred twelve patients who displayed immediate graft function were included in the study group to analyze donor and recipient age and sex, etiology of ESRD, HLA compatibility AB0 and Rh compatibility cold ischemia time, warm ischemia time, antileukocytes antibodies (PRA), and period of dialysis therapy before transplantation. We observed statistical significance for HLA and AB0 compatibility, younger donor age, and shorter cold ischemia time as the most important factors predictive of early graft function and an improved prognosis for graft survival.
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PMID:Factors that impact on immediate graft function in patients after renal transplantation. 1452 72

Transplantation is the best treatment for end-stage renal diseases. For transplantologists, it is most important to know the factors that worsen graft survival prognosis. The aim of the study was to investigate factors predictive of graft loss and shortened graft survival. We retrospectively reviewed 442 renal transplant patients between 1990 and 1995 in two Szczecin units, all of whom received a triple-drug immunosuppressive regimen. One hundred thirty patients showed graft disorders such as delayed graft function or primary nonfunction. The occurrence of these disorders was examined as a function of donor and recipient age and sex, cause of ESRD, HLA compatibility, ABO and Rh compatibility, cold ischemia time, warm ischemia time, antileukocyte antibody level (PRA), and period of dialysis therapy before transplantation. The study showed that a high maximal PRA level, incompatibility for ABO group, and a longer warm ischemia time increase the probability of early graft function disorders.
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PMID:Impact of selected factors on early graft function in patients after renal transplantation. 1452 77

We carried out a prospective study of the safety and efficacy of daclizumab combined with triple immunosuppression in adult recipients of at least one HLA-mismatched cadaveric renal allograft. All studied patients received the same immunosuppression: a daclizumab infusion of 1 mg/kg immediately before transplantation, and at 2, 4, 6, and 8 weeks following the transplantation. Infusion of cyclosporine (CsA) (0.08 mg/kg/h) was started at the time of the operation and continued by CsA microemulsion (CsA-Neoral), 3 mg/kg twice daily on day 2, methylprednisolone, 0.4 mg/kg intravenously at operation, and mycophenolate mofetil started on day 1. The dose of CsA-Neoral was adjusted to maintain target blood trough levels. Oral methylprednisolone was tapered by 4 mg per week to achieve a maintenance dose of 0.08 mg/kg/day. Fifty-five patients, with a mean age of 48 +/- 11 years, were studied. Six of them received a second renal allograft. The mean donor age was 38 +/- 14 years. Mean cold ischemia time was 19.5 +/- 6.5 h, mean value of HLA-antigen mismatches was 2.7 +/- 0.9, mean latest PRA value was 3 +/- 7%. Fifteen patients experienced delayed graft function. During a follow-up period of 3 months three acute rejection episodes occurred. One patient died because of systemic aspergillosis. After 3 months mean serum creatinine was 104 +/- 38 micromol/L. Five renal allografts failed, one of them due to rejection. Patient and graft survival was 98.2% and 90.9%, respectively. Daclizumab with this triple therapy represents safe and efficient immunosuppression strategy, demonstrated with low incidence of early acute rejection episodes and an acceptable adverse event profile in cadaveric renal allograft recipients.
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PMID:Prevention of early acute rejection with daclizumab and triple immunosuppression in cadaveric renal allograft recipients. 1596 3

Persistent shortage of kidneys for transplantation has forced most transplant centers to include procurement and use of kidneys from older donors. It is not clear whether the optimal use of these kidneys involve age-matching to the recipient. The aim of this study was to evaluate the clinical outcome of older cadaveric kidneys (>60 years), transplanted to young recipients (<50 years) and older recipients (>60 years). From 1989 through 2002, 252 first kidney grafts were procured from donors above the age of 60; 149 of the recipients to these grafts were above 60 years and 45 recipients were below 50. Minimum follow-up time was 12 months. Variables for waiting time to transplantation, DR mismatches, PRA, dialysis prior to transplantation, episodes of acute rejection, number of steroid-resistant rejections, creatinine levels, cold ischemia time, and causes of graft loss did not differ between the two groups. There was no significant difference in graft survival for young and older recipients receiving kidney from donors above 60 years of age. Graft survival at 1 year for young recipients was 90% and for older recipients 93% (NS). Five-year graft survival was 72% and 79%, respectively (NS). However, there was a significant positive effect on long-term graft survival if the donor kidney was less than 50 years. From our data, there is no evidence that age-matching of older donors has any beneficial effect on graft survival in kidney transplantation.
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PMID:Should kidneys from older cadaveric donors be age-matched to the recipient? 1629 72


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