Allograft and overall survival of patients with posttransplant skin cancer.

BACKGROUND: Little is known about the possible association between nonmelanoma skin cancer (NMSC) and allograft survival and overall patient survival. OBJECTIVE: To determine the association between posttransplant NMSC and early to mid-term allograft survival and overall patient survival after kidney, liver, or heart transplantation. METHODS AND MATERIALS: We retrospectively reviewed patients identified from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. The study included adult recipients of kidney (n=46,216), liver (n=8,049), and heart (n=8,519) transplants from 1996 to 2001. RESULTS: Multivariate analysis showed that kidney recipients with NMSC had a significantly lower risk of allograft loss (relative risk (RR)=0.55, p<.001) and death (RR=0.55; p<.001) within 5 years of transplantation than recipients without NMSC. Significantly lower risk of death was also observed for liver recipients (RR=0.28, p<.001) and heart recipients (RR=0.25; p<.001) with NMSC. CONCLUSIONS: Longer early to mid-term allograft and overall survival was seen in patients with NMSC, but long-term survival rates must be examined to determine whether mortality rates increase later for patients with NMSC, as noted in previous studies.

Impact of the donor risk index on the outcome of hepatitis C virus-positive liver transplant recipients.

We have investigated the impact of the donor risk index (DRI) on the outcome of hepatitis C virus (HCV)-infected patients undergoing liver transplantation (LTx). Retrospective analysis was performed from the Organ Procurement and Transplantation Network database (January 1, 2000 to June, 2006). The DRI was calculated as described by Feng et al. (Am J Transplant 2006;6:783-790). Model for End-Stage Liver Disease (MELD) exceptions were excluded from the analysis. Relative risk (RR) estimates of patient and graft loss were derived from Cox regression models. The Wald test was used to test the effect of the MELD score at transplant on the HCV-DRI interaction. Of the LTx recipients (16,678), 76.1% were Caucasian, and 66.7% were male; the median age was 52 (range, 18-80 years), and the mean follow-up time was 1148 days (range, 0-2959 days). Forty-six percent (n = 7675) of LTx recipients were HCV(+). The median DRI was 1.3 (range, 0.77-4.27). Increasing DRI was associated with a statistically significant increase in the RR of graft failure and patient death for both HCV(+) and HCV(-) recipients. However, HCV(+) recipients demonstrated a significantly higher increase in the RR of patient and graft loss as a function of the DRI than HCV(-) subjects, even after adjustments for several recipient factors, including MELD. In conclusion, a synergistic interaction between donor DRI and recipient HCV status exists, such that an allograft from a high-DRI donor more adversely affects the outcome of an HCV(+) recipient than that of an HCV(-) recipient.

Deceased donors with a past history of malignancy: an organ procurement and transplantation network/united network for organ sharing update.

Approximately 2% of deceased donor organ transplants result from donors with a past history of cancer. An analysis of Organ Procurement and Transplantation Network/United Network for Organ Sharing data on 39,455 deceased donors from 2000 to 2005 showed 1069 donors had a PHC, resulting in 2508 transplants, including 1236 kidneys, 891 livers, 199 hearts, 100 lungs, and 82 miscellaneous organs. The most common type of previous cancer in the donor was nonmelanoma skin cancer (n=776) followed by central nervous system malignancies (n=642) and carcinoma of the uterine cervix (n=336). One donor with a glioblastoma multiforme transmitted fatal tumors to three recipients. One donor with a history of melanoma 32 years earlier transmitted a fatal melanoma to a single recipient and, therefore, donors with a history of melanoma should not be used. Donors with a past history of cancer who have a nontraumatic cerebral hemorrhage cause concern because this hemorrhage may be the result of an unrecognized metastatic tumor.

Early mortality rates in older kidney recipients with comorbid risk factors.

BACKGROUND: There are over 60,000 candidates on the deceased donor kidney wait-list and the percentage of candidates over age 50 years continues to grow each year. National data have not previously been used to evaluate the association of comorbidities with mortality in older patients. METHODS: A multivariate analysis of 30,262 deceased donor primary kidney recipients aged 18-59 years and 8,895 aged >or=60 years evaluated the association of six recipient comorbidities on 90- and 365-day patient mortality rates. The additional effects of expanded criteria donors (ECD) and development of delayed graft function (DGF) were also evaluated. RESULTS: The 365-day mortality rate for recipients aged >or=60 years (10.5%) was more than twice that of recipients aged 18-59 years (4.4%) and comorbidities significantly increased mortality rates even higher (10.6-21.4%). The 365-day mortality rate for recipients aged >or=60 years who received an ECD kidney was 14.4% and who developed DGF was 15.9% while recipients with comorbidities but no DGF and no ECD ranged from 16.0 to 42.3%. The 365-day transplant mortality rate of recipients aged >or=60 years with comorbidities is higher than the 365-day wait-list mortality for patients with the same comorbidities, suggesting a lack of survival benefit from transplantation. CONCLUSIONS: Mortality rates for patients aged >or=60 years with comorbidities are higher than for those without comorbidities, significantly higher than for younger patients, and higher than for wait-listed patients. Thus, utility may be poorly served by allocating kidneys to older patients with comorbidities, and perhaps discussion of exclusionary listing criteria is warranted.

Hormonal therapy of the brain-dead organ donor: experimental and clinical studies.

Experiments in Cape Town in the 1980s demonstrated that acute brain death is followed by massive catecholamine release resulting in systemic hypertension, acute left ventricular failure, and multiple cardiac arrhythmias along with substantial decreases in cortisol, insulin, thyroid, and antidiuretic hormone levels, a change from aerobic to anaerobic metabolism, and increases in inflammatory cytokines. Hormonal replacement results in rapid recovery of cardiac function in both experimental animals and humans and enables significantly more organs to be transplanted. Organ Procurement and Transplantation Network/United Network for Organ Sharing multivariate studies on hormonal treatment of brain-dead donors revealed significant increases in organs transplanted and in one-year survival of kidneys and hearts.

Post-transplant de novo malignancies in renal transplant recipients: the past and present.

Post-transplant de novo malignancies are reviewed in three time periods: (i) the azathioprine (AZA) era from 1962 to 1980-1981, (ii) the cyclosporine (CYA) era (1980 to present) in which the calcineurin inhibitors, CYA and tacrolimus (TAC), were the mainstay of recipient immunosuppression, and (iii) the TOR inhibitor era starting in the year 2000. Both transplant registry and transplant center reports on malignancies occurring in the AZA era are reviewed. Reports from transplant centers and from the Cincinnati Transplant Tumor Registry (CTTR) in both the early CYA era (1980s) and the 1900-2000 CYA era are reported. Cancer incidence associated with AZA versus CYA, CYA versus TAC, and AZA versus mycophenolate mofetil (MMF) is compared in both transplant center and registry reports including new, unreported Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data from 1998 to 2003. The malignancy incidence associated with lymphocyte-depleting antibody and corticosteroid immunosuppression is discussed. Reduced malignancy incidence recently reported with TOR inhibitors is compared with that of conventional immunosuppression. Important nondrug factors influencing the incidence of post-transplant malignancies from seven single and three registry reports are detailed. The substantial role that de novo malignancies play in post-transplant mortality is discussed. Finally, management recommendations for recipients who develop de novo post-transplant malignancies are briefly presented.

Utilization of extended donor criteria liver allograft: Is the elevated risk of failure independent of the model for end-stage liver disease score of the recipient?

BACKGROUND: The goal of this analysis was to determine if outcomes from the use of extended criteria donor (ECD) livers were dependent upon the Model for End-Stage Liver Disease (MELD) score of the recipient. METHODS: The Organ Procurement and Transplantation Network (OPTN) database as of March 4, 2006 was used for the analysis. Data from 12,056 adult liver transplant (LTx) recipients between June 1, 2002 and June 30, 2005 was analyzed. The donor risk index (DRI) was calculated as previously reported. A DRI of > or =1.7 was classified as ECD. Relative risk (RR) estimates were derived from Cox regression models adjusted for DRI, recipient MELD, age, sex, ethnicity, diagnosis, and year of transplant. RESULTS: Data from 2,873 grafts falling in the ECD category (23.8%) and their recipients were analyzed. Recipients with low MELD scores (<15) received the highest proportion of ECD livers (33%). ECD livers were associated with a significant increase in the RR of graft failure within each MELD category. However, this effect held within each of the three MELD categories. CONCLUSION: The use of ECD grafts expands the organ pool at expense of increased RR of liver failure. Our analysis showed no significant interaction between DRI and MELD score of the recipient. The fact that there is no additional impact of ECD livers in recipients with high MELD scores suggests that this group of patients may benefit from this pool of grafts.

Maintenance immunosuppression with target-of-rapamycin inhibitors is associated with a reduced incidence of de novo malignancies.

BACKGROUND: Immunosuppressive drug therapy has been identified as one etiological factor in the increased incidence of and deaths from malignancies in renal transplant recipients. In animal models, calcineurin inhibitors have a positive growth effect, whereas target-of-rapamycin (TOR) inhibitors have a negative growth effect on malignant cells. METHODS: A multivariate analysis of posttransplant malignancies in 33,249 deceased donor primary solitary renal recipients reported by 264 kidney transplant programs to the Organ Procurement and Transplantation Network database from July 1, 1996 to December 31, 2001 was performed. Data were censored at 963 days to allow comparable follow-up time among drug treatment groups. The incidence and relative risks of any de novo malignancy (skin and solid) and for non-skin solid malignancies in patients receiving TOR inhibitors compared to patients receiving calcineurin inhibitors were the primary endpoints. RESULTS: The incidence rates of patients with any de novo posttransplant malignancy were 0.60% with sirolimus/everolimus alone, 0.60% with sirolimus/everolimus + cyclosporine/tacrolimus, and 1.81% with cyclosporine/tacrolimus (P<0.0001); the rates with a de novo solid tumor were 0%, 0.47%, and 1.00%, respectively. In the Cox regression model the relative risk associated with sirolimus/everolimus immunosuppression for any de novo cancer was 0.39 (95% CI: 0.24-0.64; P=0.0002) and for de novo solid cancer was 0.44 (0.24-0.82; P=0.0092). Other significant risk factors were male sex, adult age group, white race, and history of a malignancy. CONCLUSIONS: Maintenance immunosuppression with the TOR inhibitor drugs, sirolimus and everolimus, is associated with a significantly reduced risk of developing any posttransplant de novo malignancy and non-skin solid malignancy.

Skin cancer in organ transplant recipients: effect of pretransplant end-organ disease.

BACKGROUND: Solid organ transplant recipients are at increased risk for posttransplant neoplasms. OBJECTIVE: Our purpose was to determine whether various diseases causing end-organ failure are associated with different degrees of risk of skin cancer development after transplantation. METHODS: The Organ Procurement and Transplantation Network/United Network for Organ Sharing Transplant Tumor Registry was searched for the incidence of skin cancer among kidney, liver, and heart transplant recipients in the United States between 1996 and 2001. Multivariate analysis was used to determine the association between disease diagnosis and posttransplant skin cancer. RESULTS: Transplant recipients with specific pretransplant diseases, such as polycystic kidney disease and cholestatic liver disease, were at increased risk for skin cancer. Patients with diabetes mellitus had a lower incidence of skin cancer after kidney transplantation. LIMITATIONS: The study had only a brief follow-up period, indirect assessment of photodamage, and possible underreporting. CONCLUSION: Transplant recipients with a history of certain diseases warrant intensive skin cancer surveillance and strict sun-protective practices.

Reasons for non-use of recovered kidneys: the effect of donor glomerulosclerosis and creatinine clearance on graft survival.

BACKGROUND: In 2000, the United Network for Organ Sharing/Organ Procurement and Transplantation Network Registry reported 540 recovered kidneys were discarded because of biopsy results, and 210 were discarded because of poor organ function. We compared the percentage of glomerulosclerosis (GS) and creatinine clearance (CrCl) of both discarded and transplanted cadaveric kidneys and examined their effect on graft survival and function. METHODS: The cohort consisted of all cadaveric kidneys (n= 3,444) with reported biopsy results between October 25, 1999 and December 31, 2001. Graft survival was calculated by univariate and multivariate models. RESULTS: Fifty-one percent of discarded kidneys had GS of less than 20%, 27% had a CrCl greater than 80 mL/min, and 15% (129 kidneys) had both GS less than 20% and a CrCl of greater than 80 mL/min. Univariate analyses of kidneys with less than or equal to 20% GS revealed no difference in 1-year graft survival when the CrCl was greater than or less than or equal to 80 mL/min. When GS was greater than 20%, 1-year graft survival of kidneys with a CrCl of greater than 80 mL/min was significantly greater than that of kidneys with a CrCl of less than or equal to 80 mL/min. Multivariate results showed no significant difference in relative risk of graft loss with GS greater than 20% versus less than or equal to 20% when the CrCl was either 50 or 80 mL/min. With both GS less than or equal to 20% and greater than 20%, serum creatinine at 1 year was significantly lower in kidneys with CrCl greater 80 mL/min. CONCLUSIONS: Calculated donor CrCl does, and percentage GS on donor kidney biopsies does not, correlate well with 1-year graft survival and function, and percentage GS should not be used as the sole criterion for discarding recovered cadaveric kidneys.

The organ center of the United Network for Organ Sharing and twenty years of organ sharing in the United States.

The increasing size of the transplant waiting list and the increasing use of expanded criteria donors places a premium on efficient use of recovered organs. Maximal organ utilization often necessitates organ sharing between transplant organizations. Optimal organ sharing requires rapid, integrated communication of donor information combined with expedited organ transportation. For more than 20 years, the United Network for Organ Sharing's Organ Center has fulfilled this task for the United States transplant community. This overview details a brief history of United States organ sharing and the role played by the Organ Center. The current scope and modes of Organ Center operations are detailed.

Hormonal resuscitation yields more transplanted hearts, with improved early function.

BACKGROUND: Brain death results in cardiovascular instability and poor organ perfusion in many brain-dead donors. Hormonal resuscitation stabilizes certain brain-dead donors and is associated with significant increases in the numbers of organs transplanted per donor. The goal of this study was to examine the quality of hearts recovered from donors treated with hormonal resuscitation. METHODS: A retrospective analysis of 4,543 recipients of hearts recovered from brain-dead donors, reported to the United Network for Organ Sharing/Organ Procurement and Transplantation Network database between November 1, 1999, and December 31, 2001, was conducted. Hormonal resuscitation consisted of a methylprednisolone bolus and infusions of vasopressin and either triiodothyronine or l-thyroxine. Univariate and multivariate analyses were used to evaluate the quality of hearts from donors who received three-drug hormonal resuscitation (3HR) treatment versus donors who did not receive all three drugs (non-3HR). Death within 30 days and early graft dysfunction were used as endpoints. RESULTS: Hearts from 3HR donors demonstrated a 1-month survival rate of 96.2%, compared with a 92.1% survival rate for non-3HR donor hearts (P<0.01). Early graft dysfunction occurred in 5.6% of 3HR donor hearts and 11.6% of non-3HR donor hearts (P<0.01). Multivariate results demonstrated a 46% reduced odds of death within 30 days and a 48% reduced odds of early graft dysfunction. Steroids alone and steroids plus triiodothyronine/l-thyroxine also significantly reduced prolonged graft dysfunction. CONCLUSIONS: This study suggests that 3HR treatment of brain-dead donors results in increased numbers of transplanted hearts, with improved short-term graft function.

Aggressive pharmacologic donor management results in more transplanted organs.

BACKGROUND: Brain death results in adverse pathophysiologic effects in many cadaveric donors, resulting in cardiovascular instability and poor organ perfusion. Hormonal resuscitation (HR) has been reported to stabilize and improve cardiac function in brain-dead donors. The goal of this study was to examine the effect of HR on the brain-dead donor on the number of organs transplanted per donor. METHODS: A retrospective analysis of all brain-dead donors recovered in the United States from January 1, 2000, to September 30, 2001, was conducted. HR consisted of a methylprednisolone bolus and infusions of vasopressin and either triiodothyronine or L-thyroxine. Univariate analyses and multivariate logistic regression analyses were used to detect differences between the HR group and those donors who did not receive HR. RESULTS: Of 10,292 consecutive brain-dead donors analyzed, 701 received three-drug HR. Univariate analysis showed the mean number of organs from HR donors (3.8) was 22.5% greater than that from nonhormonal resuscitation donors (3.1) (P <0.001). Multivariate analyses showed that HR was associated with the following statistically significant increased probabilities of an organ being transplanted from a donor: kidney 7.3%, heart 4.7%, liver 4.9%, lung 2.8%, and pancreas 6.0%. Extrapolation of these probabilities to the 5,921 brain-dead donors recovered in 2001 was calculated to yield a total increase of 2,053 organs. CONCLUSION: HR stabilizes certain brain-dead donors and is associated with significant increases in organs transplanted per donor.

Living kidney donors in need of kidney transplants: a report from the organ procurement and transplantation network.

BACKGROUND: Our aim was to use the Organ Procurement and Transplantation Network (OPTN) database to determine the number of renal waitlist candidates who previously had been living donors. METHODS: All living renal donors in the OPTN database were cross-checked against the renal waitlist history files. Additionally, renal transplant programs were contacted that had listed candidates as qualified for four additional allocation points available to patients who previously had donated an organ. Confirmatory phone calls to transplant programs yielded additional cases previously unreported to the United Network for Organ Sharing. RESULTS: A total of 56 previous living donors were identified as having been subsequently listed for cadaveric kidney transplantation. Forty-three have received transplants; 36 currently have functioning grafts. One died after transplantation. Two candidates died while waiting. CONCLUSIONS: Living renal donation has long-term risks that may not be apparent in the short term. The numbers here reported underestimate the actual number of living donors with renal failure, because they include only patients listed for a kidney transplant. To determine risk factors for postdonation renal failure, long-term living-donor follow-up data are needed.