UNOS DonateLife

May 30, 2003

UNOS Researchers Present Studies at Transplant Meetings

Washington, D.C. -- Researchers from the United Network for Organ Sharing (UNOS) authored several studies at the American Transplant Congress (ATC), a combined scientific session of the American Society of Transplant Surgeons and the American Society of Transplantation, May 30 - June 4 in Washington, D.C. UNOS staff researchers are authors in a total of 26 papers presented at the ATC. UNOS staff researchers are primary authors of the studies listed below. All UNOS researchers are indicated with an asterick.

Living Organ Donation: Mortality and Early Complications Among 16,395 Living Donors in the U.S.
Authors: Mary D. Ellison, Ph.D., M.S.H.A.*, Maureen A. McBride, Ph.D.*, Leah B. Edwards, Ph.D.*, Sarah E. Taranto*, Mark L. Barr, M.D., James E. Trotter, M.D., Francis L. Delmonico, M.D.

As the number of living donors continues to grow, exceeding the number of deceased organ donors each year, the transplant community is focusing more on the short- and long-term risks to living donors. In doing so, researchers examined demographics and follow-up information on 16,395 living organ donors reported to the Organ Procurement Transplantation Network (OPTN)/UNOS database between October 25, 1999 and June 30, 2002.

To date, living kidney donation appears to be relatively low risk for the donor. Living lung donation has resulted in only rare complications, but further analysis of a larger living donor cohort is needed. The National Institutes of Health is addressing adult-to-adult living liver donation safety by sponsoring a multi-center study. To address long-term living donor concerns, the OPTN is developing new approaches toward obtaining more complete living donor follow-up information in the national transplant database and last year created a living donor committee to advise its board of directors on issues affecting living donors.

Differences in Sensitization Levels Could Contribute to the Variation in Waiting Times and Survival Rates for Cadaveric Kidneys in Whites, Blacks, Hispanics, and Asians
Authors: Alan Ting, Ph.D.*, Wida S. Cherikh, Ph.D.*, Yulin Cheng, Christopher F. Bryan, Ph.D.

Wait times for a deceased donor kidney transplant vary by candidate ethnicity. It is known that Caucasians have shorter wait times compared to non-whites. As for graft survival, African Americans have the lowest graft survival rates and Asians the highest. This study measured whether panel reactive antibody (PRA) level is a significant factor in the variation of waiting times and graft outcome seen among different ethnicities. PRA measures a person’s level of  sensitivity to foreign antigens that are important in transplantation rejection.

Researchers found that sensitization levels are highest among African American transplant candidates, followed by Hispanics, whites, and Asians; which could be a contributing factor in long waiting times experienced by African Americans, but not by Asians. Sensitization levels could also correlate with graft outcome since Asians who have the best outcomes are the least sensitized, whereas African Americans have the worst relative outcome and are the most sensitized.

MELD Predicts Waiting List Mortality for Relisted Liver Transplant Patients 
Authors: Erick B. Edwards, Ph.D.*, Ann M. Harper*, Richard B. Freeman, M.D., Russell H. Wiesner, M.D.

The Model for End-Stage Liver Disease (MELD) was implemented in early 2002 to better identify urgent patients and reduce deaths among patients awaiting liver transplants. MELD is based on common, objective laboratory tests and categorizes patients on a continuous scale of urgency.

Previous studies have validated the ability of MELD to predict mortality for newly listed liver transplant candidates with chronic liver disease. However, there has been no analysis of the model s ability to predict mortality for relisted liver transplant patients not meeting the definition for Status 1, acute primary liver graft failure (The MELD system is not used for Status 1 candidates).

The study identified 182 patients with a prior liver transplant who were relisted as non-Status 1 between May 24, 2001 and November 6, 2002. All patients were followed until an event such as death, transplant, or removal from the waiting list occurred or for a minimum of 90 days following the date of relisting. Based on the MELD score at relisting, concordance with 90-day mortality was computed.

The researchers concluded the MELD score is a very good indicator of 90-day mortality for relisted patients. Based on these early research results, relisted patients appear to be well served by the current MELD system.

The Impact of MELD and Other Factors on Pre-Transplant Mortality 
Authors: Erick B. Edwards, Ph.D.*, Ann M. Harper*, Richard B. Freeman, M.D.

The impact of the Model for End-Stage Liver Disease (MELD) in its individual components, and other factors were studied to estimate the relative risk of pre-transplant mortality as a function of MELD while adjusting for candidate age, gender, ethnicity, diagnosis, previous liver transplant, dialysis, and special case exceptions.

The study concluded that increases in the MELD score and MELD components are associated with an increased mortality risk on the liver waiting list. High MELD scores, particularly those of 30 and above, confer a significantly elevated risk of mortality. The risk of mortality is also significantly higher for Status 1 transplant candidates, who are not categorized by MELD scores.

Hormonal Resuscitation Associated With More Transplanted Kidneys With No Sacrifice in Quality
Authors: John D. Rosendale, M.S.*, H. Myron Kauffman, M.D.*, Maureen A. McBride, Ph.D. *, Franki L. Chabalewski, R.N., M.S.*, Jonathan G. Zaroff, M.D., Edward R. Garrity, M.D., Francis L. Delmonico, M.D., Bruce R. Rosengard, M.D.

OPTN/UNOS data reveal a growing disparity between the number of patients awaiting a kidney transplant and the number of kidneys available for transplant. One way to increase the supply is to maximize the number of transplantable kidneys from existing donors. In a previous study, hormonal resuscitation (HR), consisting of steroids, vasopressin, and T3 or T4, was associated with an increase in the number of transplantable hearts with improved early function.

This study was performed to examine the effectiveness of hormonal resuscitation in maximizing the supply of transplantable kidneys and to compare the early results of those kidneys with non-HR kidneys. Results of a multivariate analysis suggest that hormonal resuscitation was associated with a higher probability of kidneys being transplanted with no sacrifice in the quality of the organ.

Are Diabetics Less Likely to Develop Malignancies Following Kidney and Kidney-Pancreas Transplantation 
Authors: Maureen A. McBride, Ph.D.*, Wida S. Cherikh, Ph.D.*, H. Myron Kauffman, M.D.*, Jude Maghirang, M.S.*, Sandy Feng, M.D., Ph.D., Douglas W. Hanto, M.D., Ph.D.

A study examined whether diabetic patients who received either deceased donor kidney transplants or simultaneous kidney-pancreas transplants are less likely to develop post-transplant malignancies (i.e., any cancer, post-transplant lymphoproliferative disorder (PTLD), skin cancer, or solid tumor) compared to non-diabetic patients.

The research included all adult deceased donor kidney and kidney/pancreas transplant recipients reported to UNOS/OPTN between January 1, 1997 and December 31, 2000 with at least seven days post-transplant follow-up. Three transplant groups considered in the study were: kidney transplant recipients without diabetes, kidney transplant recipients with diabetes, and diabetic kidney/pancreas transplant recipients.

The results of a multivariate analysis indicated that diabetic kidney transplant recipients are significantly less likely to develop any post-transplant malignancy, skin cancer, and solid cancers than non-diabetic kidney transplant recipients. Diabetic kidney/pancreas transplant patients are less likely to develop skin cancer and solid tumors than non-diabetic kidney recipients. There was no difference in the likelihood of developing PTLD for any transplant group and no significant differences in developing any cancer including PTLD, skin, and solid tumor between diabetic kidney and kidney/pancreas recipients.

Assessment of the Survival Benefit of Transplantation Within Status for Pediatric Heart Candidates
Authors: Leah B. Edwards, Ph.D.*, John D. Rosendale, M.S.*, Mark M. Boucek, M.D.

Researchers analyzed data to determine whether the current status system for pediatric heart candidates on the OPTN/UNOS waiting list reflects medical urgency of the candidates and whether transplantation is beneficial for all statuses.

There is a statistically significant survival benefit for pediatric Status 1A (most urgent) recipients during the first year following transplant. Though there was a benefit seen for transplants in both Status 1B and Status 2 (least urgent) pediatric recipients, it did not reach statistical significance for either status during the first year when compared to remaining on the waiting list in that status. These results provide additional support for medical urgency classifications currently in place.

Impact of Donor and Recipient CMV Status on Survival and Post-Transplant Infection in Lung Transplantation
Authors: Leah B. Edwards, Ph.D.*, H. Myron Kauffman, M.D.*, Dan M. Meyer, M.D.

Since 1995, over half of lung transplant donors have tested positive for cytomegaloviris (CMV), a common virus that may cause serious illness in those being treated with immunosuppressive drugs and therapy, especially after an organ transplant. Between 1995 and 2000, 300 to 500 lung patients have died annually while on the lung transplant waiting list. The study assessed the impact of donor and recipient CMV status on mortality and the development of infection post transplant. The use of anti-viral drugs was also examined to assess whether the impact of CMV was lessened with use.

The highest risk was found in organ transplants involving CMV-positive donors and CMV-negative recipients, while the lowest risk was found with CMV-negative donors used for CMV postive lung transplant recipients. However, these risks must be evaluated with the possible increase in waiting list mortality associated with waiting for a CMV-negative donor.

Is There an Effect of Induction Immunosuppression on PTLD and Graft/Patient Survival After Kidney Transplantation 
Embargo until Wednesday, June 4 at 11:30 a.m. Eastern
Authors: Wida S. Cherikh, Ph.D.*, H. Myron Kauffman, M.D.*, Maureen A. McBride, Ph.D.*, Jude Maghirang, M.S.*, Lode J. Swinnen, M.D., Douglas W. Hanto, M.D., Ph.D.

The types of induction immunosuppression regimens were evaluated to determine the incidence of post-transplant lymphoproliferative disease (PTLD) and graft and patient survival after primary deceased and living donor kidney transplants. The study included more than 38,000 primary kidney transplant recipients from January 1, 1997 through December 31, 2000 who had at least seven days of survival and patients who were reported to have been treated with monoclonal antilymphocyte, polyclonal antilymphocyte, IL-2 receptor antibody, or no induction immunosuppression therapies. 

Based on a multivariate analysis it was concluded that the IL-2 receptor antibody was associated with the smallest risk of PTLD and improved survival rate. The benefit of introducing various routine induction therapies for kidney transplant recipients should be weighed against the risk of developing PTLD.

Is Induction Immunosuppression Beneficial for Graft Survival in High Risk Kidney Transplant Recipients   
Authors: Wida Cherikh, Ph.D.*, Sandy Feng, M.D., Ph.D., A.J. Bleyer, M.D., H. Myron Kauffman, M.D.*

The researchers evaluated the benefit of various induction immunosuppression therapies on graft survival in kidney transplant recipients, especially in high-risk recipients. High-risk recipients  included patients with previous transplants, delayed graft function (DGF), panel reactive antibodies (PRA) of 60 percent or more, or of African American ethnicity.

The analysis concluded that interleukin-2 (IL-2) receptor antibody was associated with significantly improved graft survival compared to polyclonal antilymphocyte, monoclonal antilymphocyte, or no induction immunosuppression therapy in baseline recipients (i.e., non-African American recipients with primary transplant, and PRA less than 60 percent).  Interleukin-2 receptor antibody was also associated with improved survival in African American recipients and recipients with panel reactive antibody of 60 percent or more. However, induction therapies were not associated with improved survival in recipients with previous transplants or delayed graft function.

Re-examination of Glomerulosclerosis as the Primary Reason for Non-Use of Recovered Cadaveric Kidneys
Authors: Erick B. Edwards, Ph.D.*, H. Myron Kauffman, M.D.*, D.G. Maluf, M.D., Mark P. Posner, M.D.

Researchers re-examined the use of glomerulosclerosis (GS) levels as the primary reason for kidney discards in an attempt to determine if some kidneys are discarded unnecessarily. Glomerulosclerosis is the scarring of the kidney associated with hypertension and disease of the renal arterioles. Clinicians have concluded that it contributes to graft loss or other complications post-transplant.

Research concluded that a GS level of greater than 20 percent should not be the sole criteria for discarding deceased donor kidneys. Donor age, renal function, and biopsy findings should all be considered before rejecting a kidney as being unsatisfactory.  Kidneys with a donor creatinine clearance exceeding 80 ml/min should be considered for transplant even with a GS higher than 20 percent.