OPTN Database Research Articles

Excellent liver retransplantation outcomes in hepatitis C‐infected recipients

Survival outcomes for liver retransplantation (LRTx) after graft loss in HCV patients (HCV-LRTx) are generally considered inferior to those after non-HCV-LRTx. Between January 1, 2005 and June 30, 2011, our center performed 663 LTx, including 116 (17.5%) LRTx, 41 (35.3%) of which were more than 90 d after the LTx. Twenty-nine (70.7%) LRTx were performed in HCV antibody-positive individuals. We compared patient demographics, baseline characteristics and outcomes of our HCV-LRTx group with the HCV-LRTx patients from the most recent OPTN database covering the same time period. Our Kaplan-Meier HCV-LRTx one-, three-, and five-yr HCV-LRTx patient survival rates were 86.2%, 79.0%, and 72.4%, respectively compared with the OPTN one-, three-, and five-yr HCV-LRTx survival rates of 73.3%, 59.0%, and 51.3% respectively. Likewise, our graft survival rates were higher than OPTN rates at all time points studied. We performed a higher percentage of HCV-LRTx as simultaneous liver/kidney transplants (SLK) (37.9% vs. 21.8%) and recorded shorter warm (30 ± 4 vs. 45 ± 23 min) and cold ischemic times (5:44 ± 1:53 vs. 7:36 ± 3:12 h:min). In our experience, HCV-LRTx patient and graft survival rates are comparable to LTx survival rates and are higher than the rates described by OPTN.

Influence of Race/Ethnic Differences in Pre-Transplant Panel Reactive Antibody on Outcomes in Heart Transplant Recipients

Purpose Panel reactive antibody (PRA) is used to screen patients being evaluated for heart transplantation (HT). Whether there are significant racial or ethnic differences in PRA among adults awaiting HT is poorly characterized. Our purpose was to investigate wait list characteristics and graft survival as a function of race and PRA. Methods and Materials All White, Black or Hispanic subjects age ≥18 (N=26,090) listed for their first HT between 1986 and 2012 were identified in the OPTN database. A PRA value of >10 was used to define clinically meaningful sensitization. Results Compared to whites and Hispanics, blacks were younger at listing and there was a higher proportion of females. Blacks had a higher peak PRA, and were more likely to be sensitized. Blacks were more likely to have graft failure than Whites or Hispanics (68% vs. 60% vs. 56%, p figure 1 ] Conclusions Race and level of sensitization are important predictors of graft survival. White N=21477 Black N=3021 Hispanic N=1258 p Age, yrs 52±11 46±12 49±12 Male (%) 17,171 (80) 1942 (64) 956 (76) Days on Wait List 210±293 191±300 164±270 Most recent PRA 3.6±12.8 4.3±14.0 3.9±13.1 0.006 Peak PRA 6.2±17.3 7.4±18.7 5.9±16.1 0.001 PRA >10% 2910 (14) 496 (16) 175 (14)

491 Trends in Wait-List Mortality in Children Listed for Heart Transplantation in the United States: Does Race Still Influence Outcome?

Purpose: The improvement in wait-list mortality in children listed for a heart transplant (HT) in the US has not been well characterized. Even less is known about the racial gaps in wait-list mortality, in particular how differences have evolved over time. We sought to assess trends in overall and race-specific pediatric HT wait-list mortality in the US during the last 20 yrs. Methods and Materials: All children 18 yrs of age listed for a primary HT in the US during 1989-2009 were identified using the OPTN database. Risk-adjusted wait-list mortality was assessed in 4 successive cohorts (1989-94, 95-99, 00-04 and 05-09) using Cox models. Results: Of 8096 children analyzed, 62% were white, 19% were black, 13% were Hispanic and 6% Other. There was a progressive decline in overall wait-list mortality (26%, 23%, 18% and 13% in successive eras, P 0.001) which remained significant after adjusting for age, race, diagnosis, blood type, listing status, hemodynamic support and dialysis (hazard ratio [HR] 0.70 in successive cohorts, 95% CI 0.67, 0.74) with a 67% lower risk of wait-list death in the 05-09 cohort vs. the 89-94 cohort (HR 0.33, CI 0.28, 0.39). In models stratified by race, era effect was present in all racial groups: white (HR 0.69, CI 0.64, 0.74), black (HR 0.70, CI 0.63, 0.78), Hispanic (HR 0.82, CI 0.71, 0.95) and Other (HR 0.64, CI 0.52, 0.79). In models stratified by era, minority children were not at higher risk of wait-list death vs. white children in the most recent cohort.

H-Y Antigen Incompatibility Not Associated with Adverse Immunologic Graft Outcomes: Deceased Donor Pair Analysis of the OPTN Database

Background. H-Y antigen incompatibility adversely impacts bone marrow transplants however, the relevance of these antigens in kidney transplantation is uncertain. Three previous retrospective studies of kidney transplant databases have produced conflicting results. Methods. This study analyzed the Organ Procurement and Transplantation Network database between 1997 and 2009 using male deceased donor kidney transplant pairs in which the recipient genders were discordant. Death censored graft survival at six months, five, and ten years, treated acute rejection at six months and one year, and rates of graft failure by cause were the primary endpoints analyzed. Results. Death censored graft survival at six months was significantly worse for female recipients. Analysis of the causes of graft failure at six months revealed that the difference in death censored graft survival was due primarily to nonimmunologic graft failures. The adjusted and unadjusted death censored graft survivals at five and ten years were similar between the two genders as were the rates of immunologic graft failure. No difference in the rates of treated acute rejection at six months and one year was seen between the two genders. Conclusions. Male donor to female recipient discordance had no discernable effect on immunologically mediated kidney graft outcomes in the era of modern immunosuppression.

HLA mismatches influence lung transplant recipient survival, bronchiolitis obliterans and rejection: Implications for donor lung allocation

Human leukocyte antigen (HLA) histocompatibility is not considered when placing donor allografts for lung transplantation. We previously reported that fewer individual Class I (HLA-A and -B) and Class II (HLA-DR) antigen mismatches (MM) correlated with improved survival in lung transplant recipients. In this study we evaluated whether the effects of total HLA, Class I and Class II MM were more important determinants of: (1) recipient survival; (2) development of bronchiolitis obliterans (BO); and (3) freedom from acute rejection (AR). All adult primary cadaveric lung recipients transplanted between April 1, 1994, and June 30, 2004 entered in the OPTN database were included (n = 9,791). Groups were created based on the total number of HLA, Class I and Class II MM. Recipient survival, freedom from AR and freedom from BO were compared. Univariate data were computed using the Kaplan-Meier method and compared by log-rank test. Multivariate analysis was performed using the Cox proportional hazards method. Univariate analysis identified significantly improved survival in recipients with fewer total HLA (p < 0.001) and Class I MM (p = 0.005). The incidence of BO was significantly lower in patients with fewer total Class I MM (p = 0.036). AR was influenced only by Class II MM (p = 0.005). By multivariate analysis, total HLA, Class I and Class II MM impacted recipient survival. Total HLA and Class I MM correlated with development of BO. Class II MM correlated with development of AR. HLA MM are important determinants of lung transplant survival, BO and AR. These data suggest that donor-recipient HLA MM may warrant consideration when allocating organs for lung transplantation.

Retransplantation After BK Virus Nephropathy in Prior Kidney Transplant: An OPTN Database Analysis

BK virus (BKV) has emerged as a major complication of kidney transplantation. Since June 30, 2004, the OPTN in the USA collects BKV as a primary or secondary cause of graft loss and also if treatment for BK virus (TBKV) is administered. In this study, we determined characteristics of those recipients of repeat kidney transplants from the OPTN database, where either (a) a graft loss occurred between June 30, 2004 and December 31, 2008 and database recorded prior TBKV in that allograft or (b) a graft loss between June 30, 2004 and December 31, 2008 was attributed primarily or secondarily due to BKV. In the study time period, 823 graft losses have occurred where TBKV or graft failure attributable to BKV was reported in prior transplant; of these, 126 have received a retransplant as of June 5, 2009. Induction and maintenance immunosuppression usage mirrored current trends. As of June 5, 2009, 118/126 grafts are still functioning, one graft failure attributed to BKV. TBKV was reported in 17.5% of the retransplants. In the retransplants performed through December 31, 2007, 1-year acute rejection rate was 7%, 1-year and 3-year Kaplan-Meier graft survival rates and median GFR were 98.5%, 93.6%, 65.5 and 68.4 mL/min, respectively. Retransplantation after BKV appears to be associated with good results.

The relationship of donor source and age on short‐ and long‐term allograft survival in pediatric renal transplantation

Limited pediatric data on allograft survival from advanced aged kidney donors exist. To determine the influence of donor source and age on allograft survival in pediatric renal transplant recipients, we analyzed the OPTN database. Allograft survival for 7291 pediatric renal transplants was evaluated. Up to five yr post-transplantation, graft survival was higher for LD vs. DD recipients. At seven yr, allograft survival was 71% in 18-54 yr-old LD recipients, 59.1% in >or=55 yr-old LD, and 45.1% in >or=50 yr-old DD recipients. An approximate 35% improvement in allograft survival in 18-54 yr-old LD recipients was observed. Multivariate results showed that recipients of LD 35-49 (aRR 0.66, 95% CI 0.55-0.80) and LD 50-54 (aRR 0.65, 95% CI 0.45-0.94) have a graft survival advantage over the ideal DD. In LD >or=55 yr, no improvement in graft survival was observed when compared with the 18-34 yr-old DD. In summary, we observed in a pediatric population, <55 yr-old LD kidneys afford improved long-term allograft survival when compared with DD kidney recipients. Increasing awareness of the long-term graft survival advantage for children receiving an LD kidney, even from older donors, should be a priority.

A comparison of CF and non-CF school-age children undergoing lung transplantation

Cystic fibrosis (CF) is a genetic disorder resulting in a chloride channel (CFTR) defect characterized by multi-organ damage. The primary cause of morbidity and mortality is end-stage obstructive lung disease. Lung transplantation is a treatment option, but is complicated by the risks of acute rejection, Bronchiolitis Obliterans syndrome (BOS) (graft dysfunction), and serious infection. This study sought to assess survival free from three major complications, namely BOS, acute rejection, and serious infection and also to compare overall survival among school-age CF transplantation recipients to non-CF recipients. We limited consideration to school-age children because they comprise a unique cohort in terms of linear and graft growth, immunity, pharmacokinetics and infection exposure as compared with infants, adolescents and adults. The OPTN national database was searched for period between January 1997 and August 2006 for children between 6 and 10 years of age undergoing lung transplantation. Children with CF were compared with non-CF recipients with regard to occurrence of BOS, infection-related hospitalizations, and acute rejections. Kaplan-Meier analyses were used for statistical comparisons of the two cohorts. There were 50 CF patients and 37 non-CF patients available for analysis from the OPTN database. Up to 5 years post-transplant, there were no statistically significant differences between CF and non-CF patients in overall survival, and survival free from BOS, acute rejections, or serious infections defined as those requiring hospitalization. Despite having an underlying systemic disease based on defective CFTR, CF school-age children receiving a lung transplant do not demonstrate more major complications or lower survival than non-CF children.

Organ Procurement and Transplantation Network/United Network for Organ Sharing Histocompatibility Committee Collaborative Study to Evaluate Prediction of Crossmatch Results in Highly Sensitized Patients

The requirement for a prospective crossmatch limits some organ allocation to local areas. The delay necessitated by the crossmatch restricts the distance across which offers can be made without unduly increasing the ischemia time. A collaborative study involving 14 transplant centers was undertaken by the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) Histocompatibility Committee to evaluate the accuracy with which the detection of unacceptable human leukocyte antigen (HLA) antigens by most advanced solid phase immunoassays can predict crossmatch results. In addition, using actual patients' unacceptable HLA antigens, the number of compatible donors that would have been available from the OPTN deceased kidney donors during 2002 to 2004 were investigated. Panel reactive antibodies were performed by conventional or solid phase assays, and crossmatches were performed by cytotoxicity or flow cytometry. Analyses were stratified for T and B cell and by method of identifying unacceptable HLA antigens and crossmatch techniques. Combination of solid phase immunoassays and flow cytometry crossmatches resulted in a higher prediction rates of positive T cell (86.1%-93.5%) and B-cell crossmatches (91%-97.8%). Prediction of negative crossmatches based on different combination of panel reactive antibodies and crossmatch techniques varied from 14.3% to 57.1%. Furthermore, numerous potential compatible donors were identified for each patient, regardless of their ethnicity, in the OPTN database, when predicted incompatible ones were excluded. The above results showed that with the advent of solid phase immunoassays, HLA antibodies can now be accurately detected resulting in prediction of crossmatch outcome. This should facilitate organ allocation and prevents shipment of organs to distant incompatible recipients.

Waitlist Mortality Decreases with Increased Use of Extended Criteria Donor Liver Grafts at Adult Liver Transplant Centers

Extended criteria donor (ECD) liver allografts are often allocated to less severely ill liver transplant (LT) candidates who are at a relatively lower risk of pretransplant mortality, but it is not clear that the use of ECD allografts will decrease center waitlist mortality (WLM). Individual patient data from the UNOS OPTN database (2002-2005) were aggregated to obtain center-specific data. Deceased donor allografts with any of the following characteristics were defined as ECDs: from a donor with any of the criteria described by the New York State Department of Health Workgroup; or 12+ h of cold ischemia. Multivariate regression was used to examine the relationship between WLM and ECD, non-ECD and LDLT use after adjusting for candidate severity of illness. A total of 3555 ECD transplants, 11,660 standard criteria donor (SCD) transplants, and 717 LDLTs were performed at 100 centers during this period. The model demonstrated that SCD and ECD LTs were inversely correlated with a center's WLM (beta=-0.242 and -0.221, respectively; p <or= 0.003 for each). LDLTs did not significantly reduce WLM (beta=-0.048, p=0.55). In summary, increasing ECD liver allograft use significantly decreased WLM at US centers. Policies encouraging the increase used of ECDs would further reduce WLM.

Liver Transplantation for Hepatitis B in the United States

Aim To evaluate the impact of hepatitis B virus (HBV) on US health care system, we reviewed the Organ Procurement and Transplantation (OPTN, formerly UNOS) HBV database. Method We reviewed records of liver transplantations (LTx) performed in the United States listed for the diagnoses of HBV between 1993 and mid-October 2004. Both acute as well as chronic cases were included. Coinfection with hepatitis C virus was excluded from study. The specific states selected for review were chosen from those areas that are receiving large numbers of new immigrants from high HBV endemic areas (ie, Texas, Pennsylvania, California, New York, and Florida). One-, 3-, and 5-year patient survival rates for both cadaveric and living related donors were analyzed. Survival rates were obtained from OPTN database as Kaplan-Meyer survival test. Results Between 1993 and mid-October 2004, 53,312 LTx had been performed nationwide. Of these, 2314 (4.34%) were performed for the diagnosis of HBV; 1816 cases (78%) were due to chronic HBV infection (45 of them were living donor LTx) and 498 cases (22%) were due to HBV-induced acute liver failure (seven of them were living donor LTx). Three- and 5-year survival rates of chronic HBV-related LTx patients were better than acute HBV-related and overall LTx patients. Conclusion HBV is generally considered to have a minor health significance by many community gastroenterologists. With growing immigration from overseas, it may eventually have a higher impact on LTx. Therefore, it is crucial to further educate gastroenterologists and primary care physicians caring for this specific group of patients.