Faculty Bibliography

BACKGROUND:The 2004 International Society for Heart and Lung Transplantation consensus report specified an entity of histopathologic antibody-mediated rejection (hAMR) but did not define specific histologic criteria. Therefore, there is no gold standard for hAMR diagnosis. METHODS:In May 2009 we performed a survey of pathologists from cardiac transplant centers in the United States and Canada assessing practices regarding hAMR investigation. RESULTS:Of 94 centers who responded to our survey (77% response rate), 90% reported investigating for hAMR, and 80% of those reported having a defined protocol. Of centers with a defined protocol, 23% investigated all biopsies for hAMR. Of those who investigated for hAMR selectively, the most common triggers were clinical suspicion (61%) or suggestive histologic findings (36%). Sixteen different stains were used for hAMR investigation, the most common being C4d by immunofluorescence (38%), immunohistochemistry (38%) or both (21%). CONCLUSIONS:We found wide variation in pathologists' practices regarding hAMR diagnosis. A consensus document regarding hAMR is needed to better align our collective protocols, understand this disease process and to optimize patient care.

BACKGROUND:The acceptance and implementation of the International Society for Heart and Lung Transplantation's most recently adopted grading system (ISHLT-2004), which supplanted the ISHLT-1990 system for diagnosing cardiac allograft rejection, are unknown. METHODS:We performed an online survey of pathologists at cardiac transplant centers in the United States and Canada to determine how cardiac transplant rejection is reported. The survey consisted of a series of questions related to biopsy volume, the rejection grading system used, and reasons why that grading system was used. RESULTS:Survey responses were obtained from 96 of 122 centers in the United States and Canada. Eighty-seven percent of respondents reported adopting the ISHLT-2004 grading system, either exclusively or in combination with other grading systems. Overall, 45% of respondents use only the ISHLT-2004 grading system, 40% issue reports containing both the ISHLT-2004 and the ISHLT-1990 grading systems, 12% use only the ISHLT-1990 system, and 3% use either the ISHLT-2004 or the ISHLT-1990 system in combination with an older scoring system. The primary reasons for not using the ISHLT-2004 grading system exclusively were (1) the perceived preference of cardiologists and cardiac surgeons at that particular center (77%) and (2) a belief that the ISHLT-2004 grading system is not as informative as the ISHLT-1990 grading system (62%). CONCLUSIONS:There is appreciable variability in the system(s) used for reporting rejection among North American cardiac transplant centers. Understanding the reasons behind this variability will be crucial for the optimization of future grading systems for cardiac allograft rejection.

Accurate assessment of the impact of donor quality on liver transplant (LT) costs has been limited by the lack of a large, multicenter study of detailed clinical and economic data. A novel, retrospective database linking information from the University HealthSystem Consortium and the Organ Procurement and Transplantation Network registry was analyzed using multivariate regression to determine the relationship between donor quality (assessed through the Donor Risk Index [DRI]), recipient illness severity, and total inpatient costs (transplant and all readmissions) for 1 year following LT. Cost data were available for 9059 LT recipients. Increasing MELD score, higher DRI, simultaneous liver-kidney transplant, female sex, and prior liver transplant were associated with increasing cost of LT (P < 0.05). MELD and DRI interact to synergistically increase the cost of LT (P < 0.05). Donors in the highest DRI quartile added close to $12,000 to the cost of transplantation and nearly $22,000 to posttransplant costs in comparison to the lowest risk donors. Among the individual components of the DRI, donation after cardiac death (increased costs by $20,769 versus brain dead donors) had the greatest impact on transplant costs. Overall, 1-year costs were increased in older donors, minority donors, nationally shared organs, and those with cold ischemic times of 7-13 hours (P < 0.05 for all). In conclusion, donor quality, as measured by the DRI, is an independent predictor of LT costs in the perioperative and postoperative periods. Centers in highly competitive regions that perform transplantation on higher MELD patients with high DRI livers may be particularly affected by the synergistic impact of these factors.

PURPOSE OF REVIEW/OBJECTIVE:High infectious risk donors (HRDs) fall into a behavioral category thought to increase risk of infectious transmission through transplantation; despite controversy surrounding their use, they comprise almost 9% of donors in which at least one organ is recovered. This review seeks to describe national patterns in utilization, attitudes toward HRDs, and strategies to minimize and quantify infectious risks. RECENT FINDINGS/RESULTS:HRD organs are discarded at a higher rate than non-HRDs, and many surgeons have decreased the use of HRDs in response to a recent widely publicized case of HIV and hepatitis C virus (HCV) transmission. Special informed consent use can mitigate legal risk and might increase provider comfort with HRD utilization. Nucleic acid testing (NAT) mitigates infectious risk by decreasing the window period, particularly for HCV in which the risk of undetected window period infection decreases by an order of magnitude. Estimated risk of undetected window period HIV infection varies by HRD behavior category (range 0.035-4.9 per 10,000 donors when NAT is used), HCV risk is higher (range 0.027-32.4 per 10.000). SUMMARY/CONCLUSIONS:Given long waiting times and high waitlist mortality, organs from HRDs can be used to expand the organ supply. Estimates of HRD infectious risk can be used to guide patient and provider decision making.

With an increasing number of individuals with end-stage organ disease and the increasing success of organ transplantation, the demand for transplants has steadily increased. This growth has led to a greater need to utilize organs from as many donors as possible. As selection criteria have become less stringent to accommodate increasing demand, transplant outcomes are more strongly influenced by recipient and donor factors; thus, finding the right organ for the right recipient is more important than ever. The Ninth Annual American Society of Transplant Surgeons (ASTS) State-of-the-Art Winter Symposium, entitled "The Right Organ for the Right Recipient," addressed the matching of donor organs to appropriate recipients. Representative dilemmas in the matching of donor organs with recipients were discussed. These included the following: matching by donor and recipient risk characteristics; use of organs with risk for disease transmission; biologic incompatibility; use of organs from donors after cardiac death; the justification for combined organ transplants like liver-kidney and kidney-pancreas; and the role of allocation in facilitating the matching of donors and recipients. Regardless of the particular issue, decisions about donor-recipient matching should be evidence-based, practical, and made with the goal of maximizing organ utilization while still protecting individual patient interests.

In light of continued uncertainty regarding postkidney donation medical, psychosocial and socioeconomic outcomes for traditional living donors and especially for donors meeting more relaxed acceptance criteria, a meeting was held in September 2010 to (1) review limitations of existing data on outcomes of living kidney donors; (2) assess and define the need for long-term follow-up of living kidney donors; (3) identify the potential system requirements, infrastructure and costs of long-term follow-up for living kidney donor outcomes in the United States and (4) explore practical options for future development and funding of United States living kidney donor data collection, metrics and endpoints. Conference participants included prior kidney donors, physicians, surgeons, medical ethicists, social scientists, donor coordinators, social workers, independent donor advocates and representatives of payer organizations and the federal government. The findings and recommendations generated at this meeting are presented.

Living donor kidney exchange, also referred to as kidney paired donation (KPD), is a relatively new transplant modality that is growing by leaps and bounds in the U.S. From its first realization as an exchange of kidneys between two incompatible donor/recipient pairs, KPD has expanded to include compatible pairs, nondirected donors, three-way and larger exchanges, and living/deceased donor exchanges. Innovations both clinical (transporting organs instead of donors, and improved HLA screening) and mathematical (simulation to test policies, optimization to find better and more matches) have made this modality even more useful and accessible. There are several independent multi-center paired donation registries and many more single-center registries operating in the U.S., but incompatible pairs are most likely to match when they participate in the largest possible paired exchange pool; a single, unified KPD program in the United States would likely best serve patients in search of matches.