Over the past 65 years, kidney transplantation has evolved into the optimal treatment for patients with kidney failure, dramatically reducing suffering through improved survival and quality of life. However, access to transplant is still limited by organ supply, opportunities for transplant are inequitably distributed, and lifelong transplant survival remains elusive. To address these persistent needs, the National Kidney Foundation convened an expert panel to define an agenda for future research. The key priorities identified by the panel center on the needs to develop and evaluate strategies to expand living donation, improve waitlist management and transplant readiness, maximize use of available deceased donor organs, and extend allograft longevity. Strategies targeting the critical goal of decreasing organ discard that warrant research investment include educating patients and clinicians about potential benefits of accepting nonstandard organs, use of novel organ assessment technologies and real-time decision support, and approaches to preserve and resuscitate allografts before implantation. The development of personalized strategies to reduce the burden of lifelong immunosuppression and support "one transplant for life" was also identified as a vital priority. The panel noted the specific goal of improving transplant access and graft survival for children with kidney failure. This ambitious agenda will focus research investment to promote greater equity and efficiency in access to transplantation, and help sustain long-term benefits of the gift of life for more patients in need.

Controlled donation after circulatory determination of death (DCD), where death is determined after cardiac arrest, has been responsible for the largest quantitative increase in Canadian organ donation and transplants, but not for heart transplants. Innovative international advances in DCD heart transplantation include direct procurement and perfusion (DPP) and normothermic regional perfusion (NRP). After death is determined, DPP involves removal and reanimation of the arrested heart on an ex situ organ perfusion system. Normothermic regional perfusion involves surgically interrupting (ligating the aortic arch vessels) brain blood flow after death determination, followed by restarting the heart and circulation in situ using extracorporeal membrane oxygenation. The objectives of this Canadian consensus building process by a multidisciplinary group of Canadian stakeholders were to review current evidence and international DCD heart experience, comparatively evaluate international protocols with existing Canadian medical, legal, and ethical practices, and to discuss implementation barriers. Review of current evidence and international experience of DCD heart donation (DPP and NRP) determined that DCD heart donation could be used to provide opportunities for more heart transplants in Canada, saving additional lives. Although candid discussion identified a number of potential barriers and challenges for implementing DCD heart donation in Canada, it was determined that DPP implementation is feasible (pending regulatory approval for the use of an ex situ perfusion device in humans) and in alignment with current medical guidelines for DCD. Nevertheless, further work is required to evaluate the consistency of NRP with current Canadian death determination policy and to ensure the absence of brain perfusion during this process.

Heart and lung procurements are multiphased processes often accompanied by an array of complex logistics. Approaches to donor evaluation and management, organ procurement, and organ preservation vary among individual procurement teams. Because early graft failure remains a major cause of mortality in contemporary thoracic organ transplant recipients, we sought to establish some standardization in the procurement process. This paper, in this vein, represents an international consensus statement on donor heart and lung procurement and is designed to serve as a guide for physicians, surgeons, and other providers who manage donors to best optimize the clinical status for the procurement of both heart and lungs for transplantation. Donation after brain death (DBD) and donation after circulatory determination death (referred to as donation after circulatory death [DCD] for the remainder of the paper) for both heart and lung transplantation will be discussed in this paper. Although the data available on DCD heart donation are limited, information regarding the surgical technique for procurement is included within this consensus statement. Furthermore, this paper will focus on adult DBD and DCD heart and lung procurement. Currently, no certification, which is either recognized and/or endorsed by the transplant community at large, exists for the training of a cardiothoracic procurement surgeon. Nevertheless, establishing a training curriculum and credentialing requirements are beyond the scope of this paper.

Simultaneous pancreas-kidney (SPK) transplantation remains the most effective treatment for providing consistent and long-term euglycemia in patients having type 1 diabetes with renal failure. Thrombosis of the pancreatic vasculature continues to contribute significantly to early graft failure and loss. We compared the rate of thrombosis to graft loss and systematically reviewed risk factors impacting early thrombosis of the pancreas allograft following SPK transplantation. We searched the MEDLINE, EMBASE, The Cochrane Library, and PREMEDLINE databases for studies reporting thrombosis following pancreas transplantation. Identified publications were screened for inclusion and synthesized into a data extraction sheet. Sixty-three studies satisfied eligibility criteria: 39 cohort studies, 22 conference abstracts, and 2 meta-analyses. Newcastle-Ottawa Scale appraisal of included studies demonstrated cohort studies of low bias risk; 1127 thrombi were identified in 15 936 deceased donor, whole pancreas transplants, conferring a 7.07% overall thrombosis rate. Thrombosis resulted in pancreatic allograft loss in 83.3% of reported cases. This review has established significant associations between donor and recipient characteristics, procurement and preservation methodology, transplantation technique, postoperative management, and increased risk of early thrombosis in the pancreas allograft. Further studies examining the type of organ preservation fluid, prophylactic heparin protocol, and exocrine drainage method and early thrombosis should also be performed.

BACKGROUND:

Variable effects of steroid minimization strategies on blood pressure in pediatric renal transplant recipients have been reported, but data on the effect of steroid withdrawal on ambulatory blood pressure and circadian blood pressure rhythm have not been published so far.

METHODS:

In a prospective, randomized, multicenter study on steroid withdrawal in pediatric renal transplant recipients (n = 42) on cyclosporine, mycophenolate mofetil, and methylprednisolone, we performed a substudy in 28 patients, aged 11.2 ± 3.8 years, for whom ambulatory blood pressure monitoring (ABPM) data were available.

RESULTS:

In the steroid-withdrawal group, the percentage of patients with arterial hypertension, defined as systolic and/or diastolic blood pressure values recorded by ABPM > 1.64 SDS and/or antihypertensive medication, at month 15 was significantly lower (35.7%, p = 0.002) than in controls (92.9%). The need of antihypertensive medication dropped significantly by 61.2% (p < 0.000 vs. control), while in controls, it even rose by 69.3%. One year after steroid withdrawal, no patient exhibited hypertensive blood pressure values above the 95th percentile, compared to 35.7% at baseline (p = 0.014) and to 14.3% of control (p = 0.142). The beneficial impact of steroid withdrawal was especially pronounced for nocturnal blood pressure, leading to a recovered circadian rhythm in 71.4% of patients vs. 14.3% at baseline (p = 0.002), while the percentage of controls with an abnormal circadian rhythm (35.7%) did not change.

CONCLUSIONS:

Steroid withdrawal in pediatric renal transplant recipients with well-preserved allograft function is associated with less arterial hypertension recorded by ABPM and recovery of circadian blood pressure rhythm by restoration of nocturnal blood pressure dipping.

The second edition of the British Transplantation Society Guidelines for Transplantation from Donors after Deceased Circulatory Death was published in June 2013. The guideline has been extensively revised since the previous edition in 2004 and has used the GRADE system to rate the strength of evidence and recommendations. This article summarizes the Statements of Recommendation contained in the guideline, which provide a framework for transplantation after deceased circulatory death in the U.K. and may be of wide international interest. It is recommended that the full guideline document is consulted for details of the relevant references and evidence base. This may be accessed at: http://www.bts.org.uk/MBR/Clinical/Guidelines/Current/Member/Clinical/Current_Guidelines.aspx.

The intent of the PHS guideline is to improve organ transplant recipient outcomes by reducing the risk of unexpected HIV, HBV and HCV transmission, while preserving the availability of high-quality organs. An evidence-based approach was used to identify the most relevant studies and reports on which to formulate the recommendations. This excerpt from the guideline comprises (1) the executive summary; (2) 12 criteria for assessment of risk factors for recent HIV, HBV and HCV infection; (3) 34 recommendations on risk assessment (screening) of living and deceased donors; testing of living and deceased donors; informed consent discussion with transplant candidates; testing of recipients pre- and posttransplant; collection and/or storage of donor and recipient specimens; and tracking and reporting of HIV, HBV and HCV; and (4) 20 recommendations for further study. For the PHS guideline in its entirety, including the background, methodology and primary evidence underlying the recommendations, refer to the source document in Public Health Reports, accessible at http://www.publichealthreports.org/issuecontents.cfm?Volume=128&Issue=4. For more in-depth information on the evidence base, including tables of all study-level data, refer to Solid Organ Transplantation and the Probability of Transmitting HIV, HBV or HCV: A Systematic Review to Support an Evidence-Based Guideline, accessible at http://stacks.cdc.gov/view/cdc/12164/.

Introduction : MMF, a purine analogue immunosuppressive agent, has been used as rescue therapy for calcineurin inhibitor toxicity in organ transplant recipients. Its efficacy and toxicity as primary immunosuppressive agent in paediatric liver transplant recipients has not been evaluated. Aim : To evaluate the efficacy of MMF as an additive primary immunosuppressant to a calcineurin inhibitor and steroid based immunosuppression in children. Methods : 44 (22 boys) children were prospectively randomised over 4 yrs, Group A (Cyclosporine + azathioprine + steroids)-11, Group B (Cyclosporine + MMF + steroids)-7, Group C (Tacrolimus + steroids)-12 and Group D (Tacrolimus + MMF + steroids)-14. From September 2002 primary immunosuppression was changed from Cyclosporine to Tacrolimus. The blood levels of Cyclosporine and Tacrolimus in groups B & D were maintained at 30-50% lower compared to group A & C respectively. Children were monitored for incidence of rejection, sepsis, renal function (51 Cr-EDTA GFR) and side effects of MMF. Results : Median age at the time of transplantation was 1.45 yrs (0.44 - 13.6). The indications of transplantation were biliary atresia (31), Alagille syndrome (3), alpha-1-antitrypsin deficiency (2), metabolic liver disease (2), BSEP deficiency (2), others (4).At a median follow up period of 1.54 yrs (0.01- 3.82), graft and patient survival was not significantly different in the groups. The incidence of acute cellular rejection(ACR) tended to be lower in MMF treated children (Groups B & D)[table 1]. The incidence of viral, bacterial and fungal infections in Group A & B and Group C & D was not different (table 1). MMF treated patients had better renal function 1 yr post transplant (table 2). Side effects of MMF, diarrhoea, leucopenia, anemia were observed in 4, 2 and 1 patient respectively leading to suspension of MMF in 2. (see Table 1 and Table 2) Conclusion: This interim analysis suggests that the use of MMF as a primary immunosuppressant preserves renal function and may lower the incidence of ACR.