301.5 DELIRIUM IN PEDIATRIC TRANSPLANT PATIENTS. C. Samsel, K. McKenna. Pediatric Transplant Center, Boston Children’s Hospital, Boston, MA, United States. PURPOSE: Delirium is an under-recognized phenomenon in intensive care units and pediatrics. Over the past several years, increased attention has been given to identifying and treating this disorder and its symptoms given the significant impact on patient morbidity, mortality, and length of stay. A review of delirium incidence rates over a 6-year period at a large pediatric transplant center was conducted and screening protocols were developed to assist with identifying at-risk patients prior to transplant surgery. METHODS: Chart reviews were performed for all SOT consultations between 2008 and 2014 to collect basic demographic variables and medical history as well as delirium diagnosis and symptoms during admissions. A delirium screening checklist was then created based on available literature on risk factors and trends observed within this center. RESULTS: 1062 consultations were analyzed for 399 unique patients. Patients were diverse (32.3% non-White), evenly distributed between sexes (56.8% male), and ranged in age from 2 to 44 years old (mean=14.19). Delirium rates for the transplant patient population ranged from 12–20% by organ group and accounted for 15% of the referrals for psychopharmacological management during admissions. There was a high association with morbidity and mortality in SOT patients with delirium. In April 2016, a delirium screening protocol was initiated for all psychiatric pre-transplant evaluations. To date, 34 patients across 4 solid organ transplant programs (heart, kidney, liver, and lung) have been screened. These patients will be followed longitudinally to track whether the screening protocol adequately identified risk and assisted with prevention and treatment of delirium during medical inpatient admissions. CONCLUSION: Delirium is a significant risk factor impacting morbidity and mortality of SOT patients. No studies current exist describing or screening for delirium in pediatric SOT populations. Early identification of patients at increased likelihood of having these symptoms is imperative to improving outcomes and quality of life. Our review indicates that up to 1/5 of transplant patients are exhibiting delirium, predominately in the ICU. The screening measure is a quick intervention that can be conducted by any staff member to help facilitate planning amongst care teams preparing for medical procedures that place patients at increased risk and may result in changes in practice to prevent poor outcomes.

DOES ADENOVIRUS DISEASE IMPACT THE OUTCOMES IN THE PEDIATRIC SOLID ORGAN TRANSPLANT RECIPIENTS? O. Majorant, A. C. Kalil, Q. Fang, N. Wilson, D. F. Florescu. Infectious Diseases, University of Nebraska Medical Center, Omaha, NE, United States. INTRODUCTION: Adenoviruses (AdV) have emerged as important pathogens in the solid organ transplant (SOT) recipients. The aim of the study was to compare outcomes between patients with AdV disease vs. AdV shedding. METHODS: This was a retrospective study of pediatric SOT recipients who tested positive for AdV between January 1st 2004 and March 12th 2014. The patients were divided in 2 groups: patients with AdV shedding and patients with AdV disease. The demographics and outcomes were compared using Wilcoxon rank – sum for continuous variables and the chi – square tests or Fisher exact tests for categorical variables. RESULTS: We included 104 patients, with the mean age of 2.8 years (SD 3.3); 50.96% males; 21.15% of the patients were diagnosed with AdV disease, and 78.85% with AdV shedding. Table 1 describes the demographics of the cohort. Median time from transplant to AdV positive testing was 137 days (11–4481 days) in the disease group and 212.5 days (2–2653 days) in the shedding group. Table 2 describes the outcomes. CONCLUSION: AdV disease is associated with significantly lower survival of pediatric SOT recipients compared to those with AdV shedding, but it has no impact on rejection rate or graft loss. REFERENCES: 1. 1. Kathrin Seidemann, Albert Heim, Eva D. Pfister, Harald Koditz, Andreas Beilken et al.: Monitoring of Adenovirus Infection in Pediatric Transplant Recipients by Quantitative PCR: Report of Six Cases and Review of the Literature Am J Transplant 2004 Dec 4(12):2102–8. 2. 2. Marcela Echavarria: Adenoviruses in Immunocompromised Hosts Clinical Microbiology Reviews Oct.2008, p.704 – 715. 3. 3. Gwen E. McLaughlin, Spiros Delis, Lutifat Kashimawo et al.: Adenovirus Infection in Pediatric Liver and Intestinal Transplant recipients: Utility of DNA detection by PCR American Journal of Transplantation 2003;3(2):224–228. 4. 4. Parizhskaya, M., Walpusk, J., Mazariegos, G. et al. Enteric Adenovirus Infection in Pediatric Small Bowel Transplant Recipients Pediatr. Dev. Pathol. (2001) 4: 122. 5. 5. Diana D. Florescu et al. Adenovirus Infections in Pediatric Small Bowel Transplant Recipients Transplantation 2010 Jul 27;90(2):198–204. 6. 6. Michael MG, Green M, Wald ER et al.: Adenovirus infection in pediatric liver transplant recipients J Infect Dis 1992; 165: 170. 7. 7. Hoffman JA: Adenoviral disease in pediatric solid organ recipients Pediatr Transplant 2006; 10:17.

Purpose: The role of antibody-mediated rejection (AMR) for late kidney transplant failure in pediatric renal transplant (RTx) recipients is poorly defined. We therefore investigated the frequency of anti-HLA donor-specific antibodies (DSA) in patients requiring a late (>1 year post-transplant) indication graft biopsy, and the association of these findings with graft outcome. Methods: 54 patients undergoing a late biopsy between January 2005 and June 2012 at our institution were investigated. Inclusion criteria were 1st RTx and a transplant date after December 1998. Patients were tested for DSA using the LABScreen Luminex kit (One Lambda, Canoga Park, CA, USA) at the time of biopsy and pre-transplant. A mean fluorescence intensity (MFI) of >500 was used to define the cutoff for antibody positivity. Results: 21/54 (39%) of the tested patient sera were DSA positive at the time of biopsy. In 20/54 patients (37%) the DSA were directed against HLA class II antigens; class II DQ and DR DSA occurred with the same frequency (12/20 and 13/20). In 10/54 patients (19%), the DSA were directed against class I and in 9/54 patients (17%) against both class I and II. 60% of these antibodies were de novo DSA. The DSA+ cohort showed significantly (p=0.02) more often proteinuria than the DSA- cohort. Median follow-up was 44 months. The 4-year graft survival was significantly inferior in the DSA+ (42%) compared to the DSA- cohort (89%; p=0.002, log-rank test). Patients with DSA and positive C4d staining in the graft biopsy showed the worst outcome (24% graft survival at 4 years). Overall 13 grafts failed; 10/13 (77%) patients were DSA positive, 2/13 were DSA negative, but C4d positive, and 1 graft was lost due to treatment-resistant acute T-cell mediated rejection. Maximal MFI of class II DSA was significantly (p=0.01) higher in the group with graft failure. eGFR <30 ml/min·1.73 m2 (hazard ratio (HR) 3.8), DSA positivity (HR 5.4) and positive C4d staining (HR 3.4) were significant factors associated with graft loss. Conclusions: Anti-HLA DSA at the time of a late graft biopsy for clinical indication in pediatric RTx recipients is primarily against class II antigens and associates with subsequent graft failure. As many as 92% of the graft failures in this cohort could be attributed to AMR.

Purpose: Prevention of CMV infections remains a major issue in paediatric transplantation. Previous paediatric studies have focussed on the pharmacokinetics and the effect of antiviral prophylaxis with (val-)ganciclovir (VGCV); but controlled studies are lacking. Methods: In the framework of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) Registry, we therefore analysed the efficacy and safety of VGCV prophylaxis according to a standardized protocol in 159 paediatric kidney allograft recipients, aged 10.5 ± 5.5 years. 70 patients received VGCV for at least 3 months post-transplant (prophylaxis group), 89 patients without VGCV served as controls. Both cohorts were comparable in terms of age, number of living donations, HLA mismatches, cold ischemia time, initial transplant function (eGFR) and overall immunosuppressive load (Vasudev score). All patients were on a CNI-based immunosuppressive regimen; patients on mTOR inhibitors were excluded. Results: During the 3-month VGCV prophylaxis, CMV high-risk (D+/R-) patients had significantly less CMV events (infections and/or diseases) (1/32, 3%) than controls (5/13, 38%, P=0.005); after 1 and 3 years post-transplant, the rates of CMV events were numerically lower in the prophylaxis group, namely 31% vs. 38% resp. 48% vs. 67%. VGCV was well tolerated, but was associated with a higher rate of anaemia (15/70, 21% vs. 7/89, 9% in controls; P=0.026) and leukocytopenia (23% vs. 11% in controls; P=0.080). Patients contracting a CMV infection (n=27) in the 1st year post-transplant experienced a 2-fold higher rate of biopsy-proven acute rejections (BPAR) (14/27 (52%) than CMV-free recipients (36/132, 27%; P=0.023). Patients with CMV events had a lower eGFR than CMV-free patients both at 1 year (60.2 ± 24.4 vs. 68.2 ± 20.4 ml/min·1.73 m2; P=0.076) and 3 years post-transplant (51.1 ± 21.9 vs. 64.5 ± 20.6 ml/min·1.73 m2; P=0.011). Conclusions: VGCV prophylaxis is effective for CMV prophylaxis in paediatric CMV high-risk renal transplant recipients with an acceptable safety profile. CMV infections are associated with a 2-fold higher rate of BPAR and a by 20% decreased graft function at 3 years post-transplant. DISCLOSURE:Toenshoff, B.: Grant/Research Support, Research grants for clinical studies from Roche.

Controlled trials of m TOR inhibitors in children following solid organ transplantation are scarce, although evidence from prospective single‐arm studies is growing. Everolimus with reduced CNI therapy has been shown to be efficacious and safe in de novo pediatric kidney transplant patients in prospective trials. Prospective and retrospective data in children converted from CNI therapy to m TOR inhibition following kidney, liver, or heart transplantation suggest preservation of immunosuppressive efficacy. Good renal function has been maintained when m TOR inhibitors are used de novo in children following kidney transplantation or after conversion to m TOR inhibition with CNI minimization. m TOR inhibition with reduced CNI exposure is associated with a low risk for developing infection in children. Growth and development do not appear to be impaired during low‐dose m TOR inhibition, but more studies are required. No firm conclusions can be drawn as to whether m TOR inhibitors should be discontinued in children requiring surgical intervention or whether m TOR inhibition delays progression of hepatic fibrosis after pediatric liver transplantation. In conclusion, current evidence suggests that use of m TOR inhibitors in children undergoing solid organ transplantation is efficacious and safe, but a number of issues remain unresolved and further studies are required.

BACKGROUND:The results of pediatric renal transplantation have improved markedly in the last decade. However, a number of relevant clinical problems remain, such as organ damage caused by chronic rejection, long-term toxicity of immunosuppressive therapy, difficulty in developing tolerance-inducing protocols, secondary cardiovascular comorbidity, post-transplantation lymphoproliferative disease, suboptimal longitudinal growth, quality of life, adherence to immunosuppressive medication, and structured transition programs to adult care. These unmet clinical needs require intense collaborative and interdisciplinary clinical research. We recently founded the Cooperative European Paediatric Renal TransplAnt INitiative (CERTAIN; www.certain-registry.eu) as a research network and platform built on a novel, web-based registry.RESULTS:The registry's dataset provides essential information on generic kidney transplantation-related topics and also captures pediatric-specific topics, such as growth, physical and psychosocial development, and adherence. Due to its flexibility the system can be used as follows: (1) as a registry capturing a minimal or an extended dataset; (2) as a center and/or country-specific transplantation database; or (3) as a patient-specific electronic transplantation chart. The data can be exported directly from the CERTAIN web application into statistical software packages for scientific analyses. The rights regarding data ownership, evaluation, and publications are regulated in the registry's rules of procedure. Data quality is ensured by automatic software validation and a manual data review process. To avoid redundant data entry, CERTAIN has established interfaces for data change with Eurotransplant, the Collaborative Transplant Study (CTS), and the registry of the European Society of Pediatric Nephrology (ESPN) and European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) (ESPN/ERA-EDTA registry). CERTAIN fulfils all regulatory and ethical requirements of the European Union and Germany, in particular, regarding patients' data privacy and security.CONCLUSION:Using modern information technology, the recently established multinational CERTAIN Registry fills a gap in Europe for collaborative 5 research and quality assurance in the field of pediatric renal transplantation.

Introduction: So far, data on the effect of a (val-)ganciclovir-based antiviral chemoprophylaxis on the incidence of post-transplant EBV primary infection are lacking. Methods: In the framework of a prospective, multicenter trial in 106 pediatric RTx patients, we therefore performed a cohort analysis investigating the influence of (val-)ganciclovir, with or without cytomegalovirus hyperimmunoglobulin (CMV-IgG), on the incidence of EBV viremia during the first year post-transplant. 28/80 (35%) patients with known donor (D)/recipient (R) EBV serostatus bore a high risk (D+/R-) of EBV primary infection. Results: 17/28 (61%) high-risk patients developed EBV primary infection, defined as positive EBV viremia and/or EBV seroconversion, and 10/17 (59%) exhibited clinical symptoms (n=6 flu-like, n=2 infectious mononucleosis, n=2 PTLD). 4/17 (24%) patients with high, persistent EBV viremia (6.5 ± 4.9 × 104 genomes/ml) nevertheless remained asymptomatic; 3/17 (18%) were asymptomatic with low-level EBV viremia. (Val-)ganciclovir prophylaxis was associated with a significant reduction of EBV primary infection incidence in D+/R- patients (9/20 on vs. 8/8 without (val-)ganciclovir, p=0.01). Whereas at 5 months post-transplant no patient in the control group remained EBV primary infection-free, 75% of the prophylaxis group did not develop EBV primary infection; the rate of EBV primary infection-free patients at 12 months post-transplant was 55% (Fig. 1). An additive effect of CMV-IgG could not be shown (p=0.64). Type and intensity of immunosuppression, quantified according to the modified Vasudev score, had no effect either on the incidence of EBV primary infection or on the level or persistence of EBV viral load or clinical symptoms.Figure: [EBV Prophylaxis]Conclusion: Chemoprophylaxis with (val-)ganciclovir is associated with a significantly reduced incidence of EBV primary infection in high-risk pediatric kidney transplant patients.