Mary K. Guidinger

Liver transplantation in the United States, 1999-2008.

Changes in organ allocation policy in 2002 reduced the number of adult patients on the liver transplant waiting list, changed the characteristics of transplant recipients and increased the number of patients receiving simultaneous liver–kidney transplantation (SLK). The number of liver transplants peaked in 2006 and declined marginally in 2007 and 2008. During this period, there was an increase in donor age, the Donor Risk Index, the number of candidates receiving MELD exception scores and the number of recipients with hepatocellular carcinoma. In contrast, there was a decrease in retransplantation rates, and the number of patients receiving grafts from either a living donor or from donation after cardiac death. The proportion of patients with severe obesity, diabetes and renal insufficiency increased during this period. Despite increases in donor and recipient risk factors, there was a trend towards better 1‐year graft and patient survival between 1998 and 2007. Of major concern, however, were considerable regional variations in waiting time and posttransplant survival. The current status of liver transplantation in the United States between 1999 and 2008 was analyzed using SRTR data. In addition to a general summary, we have included a more detailed analysis of liver transplantation for hepatitis C, retransplantation and SLK transplantation.

A comprehensive risk quantification score for deceased donor kidneys: the kidney donor risk index.

Background. We propose a continuous kidney donor risk index (KDRI) for deceased donor kidneys, combining donor and transplant variables to quantify graft failure risk. Methods. By using national data from 1995 to 2005, we analyzed 69,440 first-time, kidney-only, deceased donor adult transplants. Cox regression was used to model the risk of death or graft loss, based on donor and transplant factors, adjusting for recipient factors. The proposed KDRI includes 14 donor and transplant factors, each found to be independently associated with graft failure or death: donor age, race, history of hypertension, history of diabetes, serum creatinine, cerebrovascular cause of death, height, weight, donation after cardiac death, hepatitis C virus status, human leukocyte antigen-B and DR mismatch, cold ischemia time, and double or en bloc transplant. The KDRI reflects the rate of graft failure relative to that of a healthy 40-year-old donor. Results. Transplants of kidneys in the highest KDRI quintile (>1.45) had an adjusted 5-year graft survival of 63%, compared with 82% and 79% in the two lowest KDRI quintiles (<0.79 and 0.79–<0.96, respectively). There is a considerable overlap in the KDRI distribution by expanded and nonexpanded criteria donor classification. Conclusions. The graded impact of KDRI on graft outcome makes it a useful decision-making tool at the time of the deceased donor kidney offer.

Kidney and pancreas Transplantation in the United States, 1996-2005

Kidney and pancreas transplantation in 2005 improved in quantity and outcome quality, despite the increasing average age of kidney graft recipients, with 56% aged 50 or older. Geography and ABO blood type contribute to the discrepancy in waiting time among the deceased donor (DD) candidates. Allocation policy changes are decreasing the median times to transplant for pediatric recipients. Overall, 6% more DD kidney transplants were performed in 2005 with slight increases in standard criteria donors (SCD) and expanded criteria donors (ECD). The largest increase (39%) was in donation after cardiac death (DCD) from non‐ECD donors. These DCD, non‐ECD kidneys had equivalent outcomes to SCD kidneys. 1‐, 3‐ and 5‐year unadjusted graft survival was 91%, 80% and 70% for non‐ECD‐DD transplants, 82%, 68% and 53% for ECD‐DD grafts, and 95%, 88% and 80% for living donor kidney transplants. In 2005, 27% of patients were discharged without steroids compared to 3% in 1999. Acute rejection decreased to 11% in 2004. There was a slight increase in the number of simultaneous pancreas‐kidney transplants (895), with fewer pancreas after kidney transplants (343 from 419 in 2004), and a stable number of pancreas alone transplants (129). Pancreas underutilization appears to be an ongoing issue.

Pediatric Transplantation in the United States, 1995–2004

Solid organ transplantation is accepted as a standard lifesaving therapy for end‐stage organ failure in children. This article reviews trends in pediatric transplantation from 1996 to 2005 using OPTN data analyzed by the Scientific Registry of Transplant Recipients. Over this period, children have contributed significantly to the donor pool, and although the number of pediatric donors has fallen from 1062 to 900, this still accounts for 12% of all deceased donors. In 2005, 2% of 89 884 candidates listed for transplantation were less than 18 years old; in 2005, 1955 children, or 7% of 28 105 recipients, received a transplant. Improvement in waiting list mortality is documented for most organs, but pretransplant mortality, especially among the youngest children, remains a concern. Posttransplant survival for both patients and allografts similarly has shown improvement throughout the period; in most cases, survival is as good as or better than that seen in adults. Examination of immunosuppressive practices shows an increasing tendency across organs toward tacrolimus‐based regimens. In addition, use of induction immunotherapy in the form of anti‐lymphocyte antibody preparations, especially the interleukin‐2 receptor antagonists, has increased steadily. Despite documented advances in care and outcomes for children undergoing transplantation, several considerations remain that require attention as we attempt to optimize transplant management.

Survival Benefit‐Based Deceased‐Donor Liver Allocation

Currently, patients awaiting deceased‐donor liver transplantation are prioritized by medical urgency. Specifically, wait‐listed chronic liver failure patients are sequenced in decreasing order of Model for End‐stage Liver Disease (MELD) score. To maximize lifetime gained through liver transplantation, posttransplant survival should be considered in prioritizing liver waiting list candidates. We evaluate a survival benefit based system for allocating deceased‐donor livers to chronic liver failure patients. Under the proposed system, at the time of offer, the transplant survival benefit score would be computed for each patient active on the waiting list. The proposed score is based on the difference in 5‐year mean lifetime (with vs. without a liver transplant) and accounts for patient and donor characteristics. The rank correlation between benefit score and MELD score is 0.67. There is great overlap in the distribution of benefit scores across MELD categories, since waiting list mortality is significantly affected by several factors. Simulation results indicate that over 2000 life‐years would be saved per year if benefit‐based allocation was implemented. The shortage of donor livers increases the need to maximize the life‐saving capacity of procured livers. Allocation of deceased‐donor livers to chronic liver failure patients would be improved by prioritizing patients by transplant survival benefit.

Rates of solid-organ wait-listing, transplantation, and survival among residents of rural and urban areas

CONTEXT Disparities in access to organ transplantation exist for racial minorities, women, and patients with lower socioeconomic status or inadequate insurance. Rural residents represent another group that may have impaired access to transplant services. OBJECTIVE To assess the association of rural residence with waiting list registration for heart, liver, and kidney transplant and rates of transplantation among wait-listed candidates. DESIGN, SETTING, AND PATIENTS Five-year US cohort of 174,630 patients who were wait-listed and who underwent heart, liver, or kidney transplantation between 1999 and 2004. MAIN OUTCOME MEASURES Rates of new waiting list registrations and transplants per million population for residents of 3 residential classifications (rural/small town population, <10,000; micropolitan, 10,000-50,000; and metropolitan >50,000 or suburb of major city). RESULTS Compared with urban residents, waiting list registration rates for rural/small town residents were significantly lower for heart (covariate-adjusted rate ratio [RR] = 0.91; 95% confidence interval [CI], 0.86-0.96; P<.002), liver (RR = 0.86; 95% CI, 0.83-0.89; P<.001), and kidney transplants (RR = 0.92; 95% CI, 0.90-0.95; P<.001). Compared with residents in urban areas, rural/small town residents had lower relative transplant rates for heart (RR = 0.88; 95% CI, 0.81-0.94; P = .004), liver (RR = 0.80; 95% CI, 0.77-0.84; P<.001), and kidney transplantation (covariate-adjusted RR = 0.90; 95% CI, 0.88-0.93; P<.001). These disparities were consistent across national organ allocation regions. Significantly longer waiting times among rural patients wait-listed for heart transplantation were observed but not for liver and kidney transplantation. There were no significant differences in posttransplantation outcomes between groups. CONCLUSIONS Patients living in rural areas had a lower rate of wait-lisiting and transplant of solid organs, but did not experience significantly different outcomes following transplant. Differences in rates of wait-listing and transplant may be due to variations in the burden of disease between different patient groups or barriers to evaluation and waiting list entry for rural residents with organ failure.

Association of center volume with outcome after liver and kidney transplantation.

Outcomes for certain surgical procedures have been linked with volume: hospitals performing a high number of procedures demonstrate better outcomes than do low‐volume centers. This study examines the effect of volume on hepatic and renal transplant outcomes. Data from the Scientific Registry of Transplant Recipients were analyzed for transplants performed from 1996–2000. Transplant centers were assigned to volume quartiles (kidney) or terciles (liver). Logistic regression models, adjusted for clinical characteristics and transplant center clustering, demonstrate the effect of transplant center volume quantile on 1‐year post‐transplant patient mortality (liver) and graft loss (kidney). The unadjusted rate of renal graft loss within 1 year was significantly lower at high volume centers (8.6%) compared with very low (9.6%), low (9.9%) and medium (9.7%) volume centers (p = 0.0014). After adjustment, kidney transplant at very low [adjusted odds ratio (AOR) 1.22; p = 0.043) and low volume (AOR 1.22 p = 0.041) centers was associated with a higher incidence of graft loss when compared with high volume centers. Unadjusted 1‐year mortality rates for liver transplant were significantly different at high (15.9%) vs. low (16.9%) or medium (14.7%) volume centers. After adjustment, low volume centers were associated with a significantly higher risk of death (AOR 1.30; p = 0.0036). There is considerable variability in the range of failure between quantiles after kidney and liver transplant. Transplant outcomes are better at high volume centers; however, there is no clear minimal threshold volume.

Portal vein thrombosis and liver transplant survival benefit.

Portal vein thrombosis (PVT) complicates the liver transplant operation and potentially affects waiting list survival. The implications on calculations of survival benefit, which balance both waiting list and posttransplant survival effects of PVT, have not been determined. The objective of this study is to describe the effect of PVT on the survival benefit of liver transplantation. Using Scientific Registry of Transplant Recipients data on adult liver transplant candidates wait‐listed between September 2001 and December 2007, Cox proportional hazard models were fitted to estimate the covariate‐adjusted effect of PVT on transplant rate, waiting list survival, and posttransplant survival. We then used sequential stratification to estimate liver transplant survival benefit by cross‐classifications defined by Model for End‐Stage Liver Disease (MELD) score and PVT status. The prevalence of reported PVT among 22,291 liver transplant recipients was 4.02% (N = 897). PVT was not a predictor of waiting list mortality (hazard ratio = 0.90, P = 0.23) but was a predictor of posttransplant mortality (hazard ratio = 1.32, P = 0.02). Overall, transplant benefit was not significantly different for patients with PVT versus without PVT (P = 0.21), but there was a shift in the benefit curve. Specifically, the threshold for transplant benefit among patients without PVT was MELD score >11 compared to MELD score >13 for patients with PVT. PVT is associated with significantly higher posttransplant mortality but does not affect waiting list mortality. Among patients with low MELD score, PVT is associated with less transplant survival benefit. Clinicians should carefully consider the risks of liver transplantation in clinically stable patients who have PVT. Liver Transpl 16:999‐1005, 2010.

Organ donation and utilization in the USA.

The processes leading to donor identification, consent, organ procurement, and allocation continue to dominate debates and efforts in the field of transplantation. A considerable shortage of donors remains while the number of patients needing organ transplantation increases.

Organ Donation and Utilization, 1995–2004: Entering the Collaborative Era

Continued progress in organ donation will help enable transplantation to alleviate the increasing incidence of end‐stage organ disease. This article discusses the implementation and effect of the federally initiated Organ Donation Breakthrough Collaborative; it then reviews organ donation data, living and deceased, from 1995 to 2004. It is the first annual report of the Scientific Registry of Transplant Recipients to include national data following initiation of the collaborative in 2003. Prior to that, annual growth in deceased donation was 2%–4%; in 2004, after initiation of the collaborative, deceased donation increased 11%. Identification and dissemination of best practices for organ donation have emphasized new strategies for improved consent, including revised approaches to minority participation, timing of requests and team design. The number of organs recovered from donation after cardiac death (DCD) grew from 64 in 1995 to 391 in 2004. While efforts are ongoing to develop methodologies for identifying expanded criteria donors (ECD) for organs other than kidney, it is clear DCD and ECD raise questions regarding cost and recovery. The number of living donor organs increased from 3493 in 1995 to 7002 in 2004; data show trends toward more living unrelated donors and those providing non‐directed donations.