COVID-19 disease among children and young adults enrolled in the North American Pediatric Renal Trials and Collaborative Studies registry.

BACKGROUND: Coronavirus disease of 2019 (COVID-19) has disproportionately affected adults with kidney disease. Data regarding outcomes among children with kidney disease are limited. The North American Pediatric Renal Trials Collaborative Studies Registry (NAPRTCS) has followed children with chronic kidney disease (CKD) since 1987 at 87 participating centers. This study aimed to evaluate the impact of COVID-19 among participants enrolled in the three arms of the registry: CKD, dialysis, and transplant. METHODS: This was a retrospective cohort study of COVID-19 among participants in the NAPRTCS CKD, dialysis, and transplant registries from 2020 to 2022. Where appropriate, t-tests, chi-square analyses, and univariate logistic regression were used to evaluate the data. RESULTS: The cohort included 1505 NAPRTCS participants with recent data entry; 260 (17%) had documented COVID-19. Infections occurred in all three registry arms, namely, 10% (n = 29) in CKD, 11% (n = 67) in dialysis, and 26% (n = 164) in transplant. The majority of participants (75%) were symptomatic. Hospitalizations occurred in 17% (n = 5) of participants with CKD, 27% (n = 18) maintenance dialysis participants, and 26% (n = 43) of transplant participants. Fourteen percent (n = 4) of CKD participants and 10% (n = 17) of transplant participants developed acute kidney injury (AKI), and a total of eight participants (one CKD, seven transplant) required dialysis initiation. Among transplant participants with moderate to severe illness, 40-43% developed AKI and 29-40% required acute dialysis. There were no reported deaths. CONCLUSIONS: COVID-19 was documented in 17% of active NAPRTCS participants. While there was no documented mortality, the majority of participants were symptomatic, and a quarter required hospitalization.

Immune urinary biomarkers predict infant cardiac surgery-associated acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) occurs frequently after infant cardiac surgery and is associated with poor outcomes, including mortality and prolonged length of stay. AKI mechanisms are poorly understood, limiting therapeutic targets. Emerging data implicates dysregulated immune activation in post-cardiac surgery AKI development. We sought to identify immune-mediated AKI biomarkers after infant cardiopulmonary bypass (CPB)-assisted cardiac surgery. METHODS: A single-center prospective study of 126 infants less than 1 year old undergoing CPB-assisted surgery enrolled between 10/2017 and 6/2019. Urine samples were collected before CPB and at 6, 24, 48, and 72 h after surgery. Immune-mediated biomarkers were measured using commercial ELISA and Luminex™ multiplex kits. Based on subject age, neonatal KDIGO (< 1 month) or KDIGO criteria defined AKI. The Kruskal-Wallis rank test determined the relationship between urinary biomarker measurements and AKI. RESULTS: A total of 35 infants (27%) developed AKI. AKI subjects were younger, underwent more complex surgery, and had longer CPB time. Subjects with AKI vs. those without AKI had higher median urinary chemokine 10 (C-X-C motif) ligand levels at 24, 48, and 72 h, respectively: 14.3 pg/ml vs. 5.3 pg/ml, 3.4 pg/ml vs. 0.8 pg/ml, and 1.15 pg/ml vs. 0.22 pg/ml (p < 0.05) post-CPB. At 6 h post-CPB, median vascular cell adhesion protein 1 (VCAM) levels (pg/mL) were higher among AKI subjects (491 pg/ml vs. 0 pg/ml, p = 0.04). CONCLUSIONS: Urinary CXCL10 and VCAM are promising pro-inflammatory biomarkers for early AKI detection and may indicate eventual AKI therapeutic targets. A higher resolution version of the Graphical abstract is available as Supplementary information.

Urine dipstick blood and acute kidney injury in infants undergoing cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with hemolysis and acute kidney injury (AKI). The study aim was to determine if urine dipstick blood in infants after CPB was associated with AKI and urine neutrophil gelatinase-associated lipocalin (NGAL). METHODS: Infants who underwent CPB at a single center were enrolled prospectively between October 2017 and June 2019. Urine samples prior to CPB and 6 h after CPB cessation were analyzed in batch for NGAL and dipstick blood. AKI was defined using creatinine-based KDIGO criteria within 72 h of CPB. Spearman correlation examined associations between urine dipstick blood and NGAL at each time point. Linear regression estimated the associations between urine dipstick blood and log-transformed NGAL 6 h after CPB. Logistic regression estimated associations and compared discrimination between urine dipstick blood and NGAL for predicting AKI. RESULTS: At baseline, 7/63 samples (11%) had > trace blood. Six hours after CPB, 62/98 samples (63%) had > trace blood and 26% had 3 + (large) blood. In total, 18/98 (18%) with a 6-h post-CPB sample had postoperative AKI. Urine dipstick blood values correlated with urine NGAL 6 h after CPB (r = 0.52, p < 0.01), but not at baseline (r = 0.06, p = 0.66). Those with 3 + (large) blood on urine dipstick had 6 times higher mean NGAL values compared to those with negative/trace blood (mean ratio 6.6, 95%CI 3.1-14.4, p < 0.01). Those with 3 + (large) blood had 8 times higher odds of AKI (OR 7.99, 95%CI 1.5-41.9, p = 0.01). CONCLUSIONS: Urine dipstick blood post CPB may be a simple and inexpensive tool to help predict AKI in infants.

Outcomes based on induction regimens in pediatric kidney transplantation: a NAPRTCS and PHIS collaborative study.

BACKGROUND: Induction agent used at the time of kidney transplant is often based upon center practice and recipient characteristics. We evaluated outcomes across induction therapies among children enrolled in the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) transplant registry with data in the Pediatric Health Information System (PHIS). METHODS: This is a retrospective study of merged data from NAPRTCS and PHIS. Participants were grouped by induction agent: interleukin-2 receptor blocker (IL-2 RB), anti-thymocyte/anti-lymphocyte globulin (ATG/ALG), and alemtuzumab. Outcomes assessed included 1-, 3-, and 5-year allograft function and survival, rejection, viral infections, malignancy, and death. RESULTS: A total of 830 children transplanted between 2010 and 2019. At 1 year post-transplant, the alemtuzumab group had higher median eGFR (86 ml/min/1.73 m2) compared to IL-2 RB and ATG/ALG (79 and 75 ml/min/1.73 m2, respectively; P < 0.001); at 3 and 5 years, there was no difference. Adjusted eGFR over time was similar across all induction agents. Rejection rates were lower among the alemtuzumab group vs. IL-2RB and ATG (13.9% vs. 27.3% and 24.6%, respectively; P = 0.006). Adjusted ATG/ALG and alemtuzumab had higher hazard ratio for time to graft failure compared to IL-2 RB (HR 2.48 and HR 2.11, respectively; P < 0.05). Incidence of malignancy, mortality, and time to first viral infection was similar. CONCLUSION: Although rejection and allograft loss rates were distinct, the incidences of viral infection and malignancy were comparable across induction agents. By 3 years post-transplant, there was no difference in eGFR. A higher resolution version of the Graphical abstract is available as Supplementary information.

Dipping at home: is it better, easier, and more convenient? A feasibility and acceptability study of a novel home urinalysis using a smartphone application.

BACKGROUND: Monitoring proteinuria in patients with kidney disease is of crucial importance given its implications for long-term disease progression and clinical management. Leveraging digital health technology to provide a clinical grade urinalysis result from home holds the potential to greatly enhance the clinical experience and workflows for patients, caregivers, and providers. The goal of this study was to evaluate the acceptability and feasibility of a home-based urinalysis kit using a smartphone application. METHODS: This is a prospective cohort study of children and young adults (5-21 years of age) at a single pediatric center. The study received ethical board approval. Families performed a home urine test using the Healthy.io smartphone app. The app was compared with standard of care of either home dipstick monitoring or urinalysis performed in clinic or a local laboratory. Patient satisfaction was compared between the new app and current practice. RESULTS: A total of 103 children, 63 (61%) male and median age 10.9 years (inter-quartile range 7.8-14.2), were enrolled. Primary diagnosis included 47 (46%) glomerular disease, 48 (47%) non-glomerular kidney disease, and 8 (8%) kidney transplant recipients. One hundred and one (98%) patients reported being satisfied with the smartphone app compared to 41 (40%) patients who were satisfied with the current practice for urine protein monitoring (p < 0.0001). Positive themes identified included ease of use, convenience, and immediacy and accuracy of results. CONCLUSIONS: The Healthy.io home urine testing app received very high rates of satisfaction among patients and caregivers compared to current practice and holds great potential to enhance patient-centered care. A higher resolution version of the Graphical abstract is available as Supplementary information.

Acute Kidney Injury in Children after Hematopoietic Cell Transplantation Is Associated with Elevated Urine CXCL10 and CXCL9.

Acute kidney injury (AKI) is nearly universally associated with worse outcomes, especially among children after hematopoietic stem cell transplant (HCT). Our objective was to examine urinary immune biomarkers of AKI after HCT to provide insights into novel mechanisms of kidney injury in this population. Studying patients undergoing allogeneic HCT provides a unique opportunity to examine immune markers of AKI because the risk of AKI is high and the immune system newly develops after transplant. Children (>2 years old) and young adults undergoing their first allogeneic HCT and enrolled in a prospective, observational cohort study at 2 large children's hospitals had urine collected pre-HCT and monthly for the first 4 months after HCT. Urine samples at each monthly time point were assayed for 8 immune-related biomarkers. AKI was defined as a 1.5-fold increase in the monthly serum creatinine value, which was recorded ±1 day from when the research urine sample was obtained, as compared with the pre-HCT baseline. Generalized estimating equation regression analysis evaluated the association between the monthly repeated measures (urinary biomarkers and AKI). A total of 176 patients were included from 2 pediatric centers. Thirty-six patients from 1 center were analyzed as a discovery cohort and the remaining 140 patients from the second center were analyzed as a validation cohort. AKI rates were 18% to 35% depending on the monthly time point after HCT. Urine CXCL10 and CXCL9 concentrations were significantly higher among children who developed AKI compared with children who did not (P < .01) in both cohorts. In order to gain a better understanding of the cellular source for these biomarkers in the urine, we also analyzed in vitro expression of CXCL10 and CXCL9 in kidney cell lines after stimulation with interferon-γ and interferon-α. HEK293-epithelial kidney cells demonstrated interferon-induced expression of CXCL10 and CXCL9, suggesting a potential mechanism driving the key finding. CXCL10 and CXCL9 are associated with AKI after HCT and are therefore promising biomarkers to guide improved diagnostic and treatment strategies for AKI in this high-risk population.

[Prevalence of H1N1 A influenza virus infection among hospitalized patients with bronchiolitis twelve months old and younger].

BACKGROUND: Many pathogens have been reported to ause bronchiolitis during the winter season including he respiratory syncytial virus (RSV), influenza, oetapneumovirus, etc. The last H1N1 A influenza pandemic ccurred during the respiratory syncytial virus (RSV) eason. The role of the pandemic influenza strain as a ause of bronchiolitis was not documented. OBJECTIVE: Assessment of the prevalence of co-infections of RSV and H1N1 influenza virus among children aged 12 months and younger, hospitalized with bronchiolitis. METHODS: A retrospective study design was used. Clinical data on 93 infants, 12 months old and younger, hospitalized for bronchiolitis, were retrospectively collected, including test results for RSV and H1N1 A influenza infection. RESULTS: Sixty-six out of the 90 (73.3 %) patients tested were positive for RSV; 2 out of the 81 patients tested (2.5%) were positive for H1N1 influenza. No patient was positive for both. CONCLUSIONS: The results of the present study clearly show that in infants younger than one year of age, who suffer from upper and lower respiratory tract infection (bronchiolitis), the main pathogen is RSV (also appeared in the middle of he H1N1 A influenza pandemic last winter). We conclude that the H1N1 A influenza infection is uncommon in infants hospitalized with bronchiolitis during the winter season.

Apnea induced by respiratory syncytial virus infection is not associated with viral invasion of the central nervous system.

We aimed to study whether direct central nervous system invasion is responsible for the neurologic manifestations seen in hospitalized infants with respiratory syncytial virus (RSV) infection. Cerebrospinal fluid from infants with RSV infection was tested for the detection of the following respiratory RNA viruses: RSV, influenza A and B, pandemic influenza H1N1, Parainfluenza-3, human metapneumovirus, adenovirus, parechovirus and enterovirus. All children tested negative for the presence of viral material in the cerebrospinal fluid. Our results support the notion that the mechanism of RSV-induced neurologic manifestations, including apnea, is not direct central nervous system invasion.

Severe infections in twins.

We describe 4 sets of twins 5 days to 10 weeks of age with a serious bacterial or viral infection. The issue of the occurrence of a simultaneous infection in twins and the clinical dilemma of the appropriate evaluation and treatment of an asymptomatic co-twin of infants with a serious infection is discussed.