May 22, 2005
UNOS Researchers Present Studies at Transplant Meetings
Seattle, Wash. -- Researchers from the United Network for Organ Sharing (UNOS) authored or will present several studies at the American Transplant Congress (ATC), a joint scientific session of the American Society of Transplant Surgeons and the American Society of Transplantation held at the Washington State Convention and Trade Center in Seattle, Wash. UNOS staff researchers are authors in a total of 24 papers being presented at ATC. Below is a listing of studies to be presented on Sunday, May 22 in which UNOS researchers are primary authors. UNOS staff researchers are indicated with an asterisk.
Justification for Status 1 Intestine Candidates: Early Data from the OPTN
Authors: Ann M. Harper*, Erick B. Edwards, Ph.D.*, Richard B. Freeman, M.D.
On June 30, 2004, the OPTN began accepting on-line submission of Status 1 justification (most urgent candidate) forms for candidates awaiting intestinal transplants. Fifty-seven percent of the Status 1 patients were pediatric, with the most common diagnosis of short gut syndrome (63 percent). To qualify for Status 1, patients must no longer have vascular access or have abnormal liver function documented by several laboratory tests. An analysis of 619 patients listed for an intestine between July 2002 and March 2005 showed 86 percent of patients listed at Status 1 at some point. Early data suggest the high proportion of Status 1 patients may indicate that medical urgency could be better differentiated. Thus it is important to monitor the reasons for upgrade to Status 1 and the outcomes of these patients.
Analysis of Early Deaths in Liver Transplantation
Authors: John D. Rosendale, M.S.*, Kim M. Olthoff, M.D.
The OPTN began collecting more precise data on the timing of transplant deaths in December 2003. Data collected is categorized as: post-anesthetic (PA), intra-operative (IO) and post-operative (PO) (first 3 days posttransplant).An analysis was conducted on the 22,240 transplants (all organs) performed between December 3, 2003 and December 31, 2005. The majority of deaths occurred in the 6,497 liver transplantsfor all three categories (PA=33, IO=36, PO=86). There was a higher percentage of early PO deaths in Status 1 (most urgent) recipients compared to non-Status 1 recipients. There was no significant difference in IO deaths based on ethnicity, but there was a higher rate of early PO deaths in African American liver recipients.
The early results of this new data collection demonstrate that the percent of all transplants that result in peri-operative death is relatively small, with the majority occurring in liver recipients, and occurring in a significant percentage of transplant centers. While Status 1, African American ethnicity, and age of the recipient are associated with a higher risk of post-operative death, with increased data collection, other variables may be identified and should continue to be closely monitored. This information may be helpful for informing patients of the overall peri-operative risk of transplantation.
Candidates With Low MELD Scores at Listing: Risk Factors for Early Mortality
Sunday, May 22 - 2:00 p.m. PST
Previous studies have shown the Model for End-stage Liver Disease (MELD) to be a good predictor of mortality on the liver waiting list; however MELD fails to discriminate between patients who will die and patients who will survive at a rate of about 15 percent. These data indicate that a significant portion of patients with lower MELD scores at listing die prematurely before receiving a liver transplant.
A cohort of patients with lower MELD scores at listing were analyzed to determine which factors in addition to MELD may be associated with early mortality. A total of 334 candidates in this cohort died within the first 90 days after listing. Of these, 177 (53 percent) died with a MELD score less than 20. MELD score at listing, age at listing, serum albumin and moderate ascites had a statistically significant impact on mortality. However, the addition of serum albumin and moderate ascites to the MELD score did not substantially improve the concordance with 90-day mortality in a more recent cohort of waiting list candidates. This demonstrates that MELD remains to be the most important predictor of pre-transplant mortality in candidates on the liver waiting list.
Association of Immunosuppression and Epstein Barr Virus (EBV) with Posttransplant Lymphoproliferative Disorder (PTLD) in Heart Recipients
Authors: Wida S. Cherikh, Ph.D.*, Lode J. Swinnen, M.D., H. Myron Kauffman, M.D.*
The incidence of Posttransplant Lymphoproliferative Disorder (PTLD) has been traditionally higher in heart recipients. However, in the last several years the number of PTLD cases in heart recipients reported to the OPTN/UNOS has been declining. Maintenance immunosuppression and EBV serostatus were examined in 4,052 heart recipients since both are major factors in determining post-transplant PTLD incidence. The incidence of PTLD was the highest with tacrolimus (TAC) with azathioprine (AZA) in EBV seronegative (18.52 percent) and seropositive patients (1.45 percent).
Results show that TAC+AZA is associated with a significantly increased risk of PTLD. EBV seronegativity with younger pediatric age was confirmed as independent significant positive risk factors for PTLD, while age greater than 55 is a newly identified risk factor.
Does the Choice of Immunosuppressive Agent Impact the Development of Renal Insufficiency Following Heart Transplantation
Authors: Leah B. Edwards, Ph.D.*, David O. Taylor, M.D.
Heart transplant recipients who developed renal insufficiency were evaluated to determine if the rate differed based on maintenance immunosuppression regimen. The study included all adult heart transplant recipients performed in the U.S. between October 25, 1999 and June 30, 2003. The study was limited to recipients on steroids, cyclosporine or tacrolimus (TAC), and azathioprine or mycophenolate mofetil at both discharge and one year. One of the strongest predictors for reducing the development of renal insufficiency from the multivariate analysis was TAC-based immunosuppression. Other predictors significant to the development of renal insufficiency included post-transplant rejection, dialysis prior to discharge, drug-treated hypertension at listing, diabetes at listing, pre-operative serum creatinine, pre-operative recipient weight and transplant center volume. In addition to the expected risk factors, the use of TAC-based immunosuppression of renal insufficiency appears to be independently associated with substantial reduction in risk of developing renal insufficiency in heart transplant recipients.
Association of Immunosuppression and Posttransplant Lymphoproliferative Disorder (PTLD) in Primary Kidney Transplant Recipients with Epstein-Barr Virus (EBV) Negative and Positive Serostatus
Authors: Wida S. Cherikh, Ph.D.*, H. Myron Kauffman, M.D.*, Douglas W. Hanto, M.D., Lode J. Swinnen, M.D.
Posttransplant Lymphoproliferative Disorder (PTLD) is a concern with transplant recipients as it is often associated with Epstein-Barr Virus (EBV). This study examined the association of induction and discharge immunosuppression and the incidence of PTLD with EBV seronegative and seropositive primary kidney transplant recipients. There were 19,540 primary kidney recipients included in the study from the OPTN/UNOS database during April 1999 to December 2002. Discharge maintenance immunosuppression included cyclosporine (CYA) or tacrolimus (TAC) with/without azathioprine (AZA) or mycophenolate mofetil (MMF).
Induction immunosuppression therapies were not associated with a statistically increased risk of PTLD in EBV seronegative patients, though there was a trend for an increased risk with anti-thymocyte globulin and a reduced risk with daclizumab. In EBV seronegative patients, TAC was associated with a significantly increased risk of PTLD, while MMF was associated with a reduced risk. In EBV seropositive patients, immunosuppression was not associated with an increased risk of PTLD. Immunosuppression appears to have a more profound association with PTLD development in EBV seronegative patients.
Excessive Mortality Rates in Older Kidney Recipients of Expanded Criteria Donor Kidneys
Authors: H. Myron Kauffman, M.D.*, Maureen A. McBride, Ph.D.*, Allan M. Roza, M.D., Francis L. Delmonico, M.D.
As the kidney waiting list continues to increase with more than 60,000 patients currently waiting resulting in increased waiting times and waiting list deaths, the transplant community attempts to make best use of the deceased donor kidney. This study examines one-year mortality in older recipients, with and without comorbidities (pre-existing secondary diagnoses), paying close attention to those who received an expanded criteria donor (ECD) kidney. Actual mortality for patients older than 60 years of age who received an ECD kidney was 14.4 percent. Mortality for those in the same age group who received a non-ECD kidney was 10.5 percent. Delayed graft function for those receiving ECD kidneys was 34.1 percent compared to non-ECD kidney recipients at 21.7 percent.
One-year mortality in older patients is extremely high, particularly when the recipients have additional comorbidities; mortality increased further with ECD kidneys. These data suggest that continued discussions are needed regarding appropriate criteria for waitlisting and suitable candidates for ECD kidney transplants.
A private, nonprofit organization, UNOS manages the nation's organ transplant system and oversees the world's most comprehensive database of clinical transplant information under contract with the federal government. UNOS operates the 24-hour computerized organ sharing system, matching donated organs to patients registered on the national organ transplant waiting list. UNOS seeks to increase organ donation through education and improve transplant success rates through outcomes-based research and policymaking. The strength of the transplant database relies on the conscientious reporting of 412 UNOS member institutions.
804-782-4730