Establishing long-term allograft acceptance without the requirement for continuous immunosuppression, a condition known as allograft tolerance, is a highly desirable therapeutic goal in solid organ transplantation. Determining which recipients would benefit from withdrawal or minimization of immunosuppression would be greatly facilitated by biomarkers predictive of tolerance. In this study, we identified the largest reported cohort to our knowledge of tolerant renal transplant recipients, as defined by stable graft function and receiving no immunosuppression for more than 1 year, and compared their gene expression profiles and peripheral blood lymphocyte subsets with those of subjects with stable graft function who are receiving immunosuppressive drugs as well as healthy controls. In addition to being associated with clinical and phenotypic parameters, renal allograft tolerance was strongly associated with a B cell signature using several assays. Tolerant subjects showed increased expression of multiple B cell differentiation genes, and a set of just 3 of these genes distinguished tolerant from nontolerant recipients in a unique test set of samples. This B cell signature was associated with upregulation of CD20 mRNA in urine sediment cells and elevated numbers of peripheral blood naive and transitional B cells in tolerant participants compared with those receiving immunosuppression. These results point to a critical role for B cells in regulating alloimmunity and provide a candidate set of genes for wider-scale screening of renal transplant recipients.

A national conference on organ donation after cardiac death (DCD) was convened to expand the practice of DCD in the continuum of quality end-of-life care.This national conference affirmed the ethical propriety of DCD as not violating the dead donor rule. Further, by new developments not previously reported, the conference resolved controversy regarding the period of circulatory cessation that determines death and allows administration of pre-recovery pharmacologic agents, it established conditions of DCD eligibility, it presented current data regarding the successful transplantation of organs from DCD, it proposed a new framework of data reporting regarding ischemic events, it made specific recommendations to agencies and organizations to remove barriers to DCD, it brought guidance regarding organ allocation and the process of informed consent and it set an action plan to address media issues. When a consensual decision is made to withdraw life support by the attending physician and patient or by the attending physician and a family member or surrogate (particularly in an intensive care unit), a routine opportunity for DCD should be available to honor the deceased donor's wishes in every donor service area (DSA) of the United States. Key words: Deceased organ donation Received 25 July 2005, revised and accepted for publication 24 October 2005A national conference on organ donation after cardiac death (DCD) was convened in Philadelphia on April 7 and 8, 2005, to address the increasing experience of DCD and to affirm the ethical propriety of transplanting organs from such donors. Participants represented the broad spectrum of the medical community, including neuroscientists, critical care professionals and distinguished bioethicists (Appendix 1).Six work groups were assembled to address specific DCD issues and fulfill the conference objectives: (i) determining death by a cardiopulmonary criterion, (ii) assessing medical criteria that predict DCD candidacy following the withdrawal of life support, (iii) reviewing protocols for successful DCD organ recovery and subsequent transplantation, (iv) initiating DCD in donation service areas (DSAs), (v) discussing the allocation of DCD organs for transplantation and (vi) examining perceptions of DCD held by the media and the public. Work Group 1: Determining Death by a Cardiopulmonary CriterionA prospective organ donor's death may be determined by either cardiopulmonary (DCD) or neurologic criteria (donation after brain death [DBD]) (1). The term donation after cardiac death (DCD) clearly indicates that death precedes donation. Death determination in the DCD patient mandates the use of a cardiopulmonary criterion to prove the absence of circulation. The cardiopulmonary criterion may be used when the donor does not fulfill brain death criteria. The ethical axiom of organ donation necessitates adherence to the dead donor rule: the retrieval of organs for transplantation should not cause the death of a donor (2).In clinical situations that fulfill either brain death criteria ...

†Drs Ferguson and Grinyo contributed equally to the work described.Current immunosuppressive regimens in renal transplantation typically include calcineurin inhibitors (CNIs) and corticosteroids, both of which have toxicities that can impair recipient and allograft health. This 1-year, randomized, controlled, open-label, exploratory study assessed two belatacept-based regimens compared to a tacrolimus (TAC)-based, steroidavoiding regimen. Recipients of living and deceased donor renal allografts were randomized 1:1:1 to receive belatacept-mycophenolate mofetil (MMF), belataceptsirolimus (SRL), or TAC-MMF. All patients received induction with 4 doses of Thymoglobulin (6 mg/kg maximum) and an associated short course of corticosteroids. Eighty-nine patients were randomized and transplanted. Acute rejection occurred in 4, 1 and 1 patient in the belatacept-MMF, belatacept-SRL and TAC-MMF groups, respectively, by Month 6; most acute rejection occurred in the first 3 months. More than twothirds of patients in the belatacept groups remained on CNI-and steroid-free regimens at 12 months and the calculated glomerular filtration rate was 8-10 mL/min higher with either belatacept regimen than with TAC-MMF. Overall safety was comparable between groups. In conclusion, primary immunosuppression with belatacept may enable the simultaneous avoidance of both CNIs and corticosteroids in recipients of living and deceased standard criteria donor kidneys, with acceptable rates of acute rejection and improved renal function relative to a TAC-based regimen.

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