COVID-19 in pediatric kidney transplantation: The Improving Renal Outcomes Collaborative.

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes

Depressive Symptoms in Children with Chronic Kidney Disease

To assess depression in children with chronic kidney disease (CKD) and to determine associations with patient characteristics, intellectual and educational levels, and health related quality of life (HRQoL)

1765. BK Polyomavirus Reactivation Outcomes After Renal Transplantation in Association With Adherence to a Standardized BK Polyomavirus Screening Protocol: A Multi-Center Collaboration

Abstract Background Reactivation of BK polyomavirus (BKPyV) due to immunosuppression after renal transplantation can lead to allograft nephropathy (BKAN) or even allograft loss. Many transplant centers implement screening protocols in an attempt to detect BKPyV reactivation before progression to BKAN, although the frequency and duration of screening vary widely among centers. Methods The New England BK Consortium (NEBKCON), a collaboration of 12 transplant centers in the northeastern United States, has adopted a standard BKPyV screening protocol (screening monthly for the first 6 months followed by screening every 3 months until 2 years after transplantation). Participating members implemented this screening protocol at their centers, and later measured adherence to the protocol as part of a NEBKCON quality improvement project. This study retrospectively analyzes BKPyV-specific outcomes in association with adherence to this protocol. Results Six centers reported data on 472 subjects who received a renal transplant between January 2016 and December 2017. Adherence to the screening protocol during the first 12 months (7.1–76.7%, mean 56.1%) and 24 months (2.9–52.5%, mean 36.8%) after transplant varied between centers. Rates of BKPyV viremia (3.6–28.2%, mean 20.6%) as well as BKAN (0–4.5%, mean 3.2%) also varied among centers. Adherence to the screening protocol was associated with a decrease in the magnitude of the initial viral load detected (3.29 vs. 3.74 log10 copies/mL, P = 0.065), but was not associated with peak viral load (3.95 vs. 4.14 log10 copies/mL, P = 0.47), viremia duration (179 vs. 196 days, P = 0.74), or incidence of BKAN among viremic subjects (15.3 vs. 16.0%, P = 0.91). Conclusion Even with a uniform screening protocol for BKPyV in place, adherence to this protocol varied widely among centers. More research is needed to determine patient-level and center-level barriers to adherence, as well as to determine optimal screening practices to further reduce the incidence of BKAN. Disclosures All authors: No reported disclosures. </jats:sec

Immune checkpoint blockade activates effective anti-tumor immunity in an orthotopic model of glioblastoma (VAC12P.1119)

Abstract Glioblastoma presents a formidable obstacle for developing immunotherapeutic strategies due to a highly immunosuppressive systemic and micro-environment. Antibody blockade of co-inhibitory receptors CTLA-4 and PD-1 has been shown to overcome immunosuppression in clinical trials of various solid tumors. We evaluated the anti-tumor efficacy of murine antibodies targeting CTLA-4 and/or PD-1 in the GL261 orthotopic, immunocompetent mouse model of glioblastoma. We observed tumor regression and long-term survival in 15% and 50% of mice treated with anti-CTLA-4 or anti-PD-1 as single agents, respectively. Combination therapy resulted in 75% of animals surviving long-term and tumor-free. Importantly, similar efficacy was observed with both early (day 7) or late (day 14) onset of treatment, thus this therapeutic strategy was effective on established tumors. Furthermore, resistance to tumor re-challenge demonstrated the generation of immunological memory in treated mice. Upon investigating the systemic and tumor immunological profile, we discovered that combination therapy increased CD8+ and NK effector cells and decreased suppressive immune cells at the tumor site and draining lymph node. In addition, combination therapy increased the serum levels of various monocyte chemo-attractant chemokines involved in immune activation. Our data provide strong support for the evaluation of immune checkpoint blockade in glioblastoma patients, and predicts potential prognostic serum biomarkers.</jats:p