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BackgroundWe report follow-up data from an ongoing prospective cohort study of COVID-19 in pediatric kidney transplantation through the Improving Renal Outcomes Collaborative (IROC).MethodsPatient-level data from the IROC registry were combined with testing, indication, and outcomes data collected to describe the epidemiology of COVID testing, treatment, and clinical outcomes; determine the incidence of a positive COVID-19 test; describe rates of COVID-19 testing; and assess for clinical predictors of a positive COVID-19 test.ResultsFrom September 2020 to February 2021, 21 centers that care for 2690 patients submitted data from 648 COVID-19 tests on 465 patients. Most patients required supportive care only and were treated as outpatients, 16% experienced inpatient care, and 5% experienced intensive care. Allograft complications were rare, with acute kidney injury most common (7%). There was 1 case of respiratory failure and 1 death attributed to COVID-19. Twelve centers that care for 1730 patients submitted complete testing data on 351 patients. The incidence of COVID-19 among patients at these centers was 4%, whereas the incidence among tested patients was 19%. Risk factors to predict a positive COVID-19 test included age > 12 years, symptoms consistent with COVID-19, and close contact with a confirmed case of COVID-19.ConclusionsDespite the increase in testing and positive tests over this study period, the incidence of allograft loss or death related to COVID-19 remained extremely low, with allograft loss or death each occurring in

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.

BACKGROUND AND OBJECTIVES: Hypertension is highly prevalent in pediatric kidney transplant recipients and contributes to cardiovascular death and graft loss. Improper blood pressure (BP) measurement limits the ability to control hypertension in this population. Here, we report multicenter efforts from the Improving Renal Outcomes Collaborative (IROC) to standardize and improve appropriate BP measurement in transplant patients. METHODS: Seventeen centers participated in structured quality improvement activities facilitated by IROC, including formal training in quality improvement methods. The primary outcome measure was the proportion of transplant clinic visits with appropriate BP measurement according to published guidelines. Prospective data were analyzed over a 12-week pre-intervention period and a 20-week active intervention period for each center and then aggregated as of the program-specific start date. We used control charts to quantify improvements across IROC centers. We applied thematic analysis to identify patterns and common themes of successful interventions. RESULTS: We analyzed data from 5392 clinic visits. At baseline, BP was measured and documented appropriately at 11% of visits. Center-specific interventions for improving BP measurement included educating clinic staff, assigning specific team member roles, and creating BP tracking tools and alerts. Appropriate BP measurement improved throughout the 20-week active intervention period to 78% of visits. CONCLUSIONS: We standardized appropriate BP measurement across 17 pediatric transplant centers using the infrastructure of the IROC learning health system and substantially improved the rate of appropriate measurement over 20 weeks. Accurate BP assessment will allow further interventions to reduce complications of hypertension in pediatric kidney transplant recipients.

Background Hypertension is a risk factor for posterior reversible encephalopathy syndrome (PRES), but the timing and severity of hypertension relative to PRES are unknown. The objective was to identify a clinically meaningful blood pressure (BP) threshold that predicts PRES development in high-risk children. Methods We recorded peak systolic BP, diastolic BP, BP z-scores, and mean arterial pressure over the 14 days preceding clinical concern for PRES in 35 subjects who developed PRES, compared to 14 controls who had normal brain magnetic resonance imaging and similar underlying disease, renal function, and medications. We used multivariable logistic regression models adjusted for fluid overload and obesity to estimate the association of peak BP with PRES. We used receiver operating characteristic curves to determine which peak BP thresholds best predicted PRES and calculated the corresponding sensitivity, specificity, and positive and negative predictive values. Results Peak systolic BP z-score was most strongly associated with PRES (OR 3.97, 95% CI 1.62-9.74), and peak systolic BP z-score [greater than or equal to] 3.0 predicted PRES (area under the curve 0.95, 95% CI 0.88-1.0) with 91% sensitivity and 85% specificity, indicating 94% positive predictive value and 79% negative predictive value. Conclusions We demonstrated that peak systolic BP z-score [greater than or equal to] 3.0 in the preceding 14 days predicted PRES development in cases compared with controls in children at high risk. Our study suggests that stage 2 hypertension, corresponding to a z-score [greater than or equal to] 3.0, could help define hypertensive emergency in high-risk children and indicate when more aggressive treatment is warranted to prevent neurologic injury., Author(s): Emily Gall [sup.1] , Abanti Chaudhuri [sup.2] , Andrew M. South [sup.3] [sup.4] [sup.5] Author Affiliations: (1) grid.67033.31, 0000 0000 8934 4045, Department of Otolaryngology-Head and Neck Surgery, Tufts [...]

Elevated blood pressures (BP) are common among hospitalized children and, if not recognized and treated promptly, can lead to potentially significant consequences. Even though we have normative BP data and well-developed guidelines for the diagnosis and management of hypertension (HTN) in the ambulatory setting, our understanding of elevated BPs and their relationship to HTN in hospitalized children is limited. Several issues have hampered our ability to diagnose and manage HTN in the inpatient setting including the common presence of physiologic conditions, which are associated with transient BP elevations (i.e., pain or anxiety), non-standard approaches to BP measurement, a lack of clarity regarding appropriate diagnostic and therapeutic thresholds, and marginal outcome data. The purpose of this review is to highlight the issues and challenges surrounding BP monitoring, assessment of elevated BPs, and the diagnosis of HTN in hospitalized children. Extrapolating from currently available clinical practice guidelines and utilizing the best data available, we aim to provide guidelines regarding evaluation and treatment of elevated BP in hospitalized children., Author(s): Abanti Chaudhuri [sup.1] , Scott M. Sutherland [sup.1] Author Affiliations: (Aff1) grid.168010.e, 0000000419368956, Division of Nephrology, Department of Pediatrics, Stanford University, , Palo Alto, California, USA Introduction Hypertension (HTN) [...]

The expansion of the number of children on the deceased donor renal transplant waitlist has far outstripped the supply of organs in most countries, leading to numerous adjustments to increase supply and to maximize the utility of donor organs. The system for organ allocation varies by country based on local laws, priorities, and resources. Adjustments are made to optimize allocation, enhance post-transplant survival benefit, decrease unequal transplant access, and optimize utilization of donated kidneys. Allocation of deceased donor kidneys is based on several criteria; however, the final decision to accept or reject the offered kidney is made by the potential recipient's transplant team (surgeon/nephrologist). Several considerations including assessment of the donor quality, the human leukocyte antigen (HLA) match between the donor and the recipient, numerous recipient factors, the geographical location of the recipient, and the organ all affect the decision to accept the organ or not for a particular recipient. This decision must be made quickly, often on the spot. Maximizing the benefit from this scarce resource raises difficult ethical issues. The philosophies of equity and utility are often competing. In this manuscript, we highlight a representative case that helps to focus on important issues for the pediatric nephrologist to consider while making the decision to accept a deceased donor kidney offer for a particular pediatric patient., Author(s): Abanti Chaudhuri[sup.1] , Gerri James[sup.1] , Paul Grimm[sup.1] Author Affiliations: (1) Department of Pediatric Nephrology, Stanford University Medical Center, 300 Pasteur Drive, 94305-5208, Stanford, CA, USA Introduction When a [...]

Background The blood pressure (BP) burden is high in pediatric hemodialysis (HD) patients and adversely affects prognosis. The aim of this study was to examine whether 44-h ambulatory BP monitoring (ABPM) provides additional relevant BP data compared with 24-h ABPM. Methods ABPM was initiated at the end of the mid-week dialysis run in 13 stable pediatric HD patients and continued until the next run for 44 h. Day 1 was defined as the initial 24-h ABPM and Day 2 as the time period after that until the next dialysis run. All patients had an echocardiogram to calculate the left ventricular mass index (LVMI). Results A higher percentage of patients were diagnosed with hypertension from the 44-h ABPM than from the 24-h ABPM. All BP indexes and loads (except nighttime diastolic load) were significantly higher on Day 2 than on Day 1. Patients with BP loads of >25 % on 44-h ABPM had significantly higher LVMI than those patients with normal BP loads. No such association was found with 24-h ABPM and LVMI. Higher interdialytic weight gain was associated with higher Day-2 nighttime systolic BP load. Conclusions The 44-h ABPM provides more information than the 24-h ABPM in terms of diagnosing and assessing the true burden of hypertension in pediatric HD patients. Elevated BP loads from 44-h ABPM correlate with a higher LVMI on the echocardiogram. Keywords Hypertension * Dialysis * Pediatric nephrology * Blood pressure * Ambulatory blood pressure monitoring, Introduction Hypertension (HTN) is a significant risk factor for cardiovascular disease in children with end-stage renal disease receiving dialysis [1]. Despite significant efforts to diagnose and treat HTN, blood pressure [...]

Background We hypothesized that the percent change in resistance (%RΔ) from bioimpedance analysis (BIA) measurements during hemodialysis (HD) can provide information on pediatric HD patients' hydration status. Methods Whole-body single-frequency BIA measurements were obtained before HD, each hour on HD, and after HD during two HD sessions. Pre-and post-HD weights, blood pressures, Crit-Line® measurements, and intradialytic symptoms were collected on the day of the BIA measurements. Results One hundred and thirty BIA measurements were obtained from 14 HD patients. The group was 43% girls, and the mean age was 13.2 ± 4.4 years. Percent change in resistance was 13.5 ± 10.8% at the end of HD; %RΔ correlated with percent body weight change (%BWΔ) following HD (r= -0.83, P Conclusions Our study showed that %RΔ strongly correlates with %BWA and %BVΔ and that %RΔ also correlated with intradialytic symptoms and LVMI. Keywords Bioimpedance * Resistance * Hemodialysis * Fluid * Hydration * Dry weight * Pediatric, Introduction Cardiovascular disease is the leading cause of mortality in pediatric patients on dialysis [1]. Chronic hypervolemia in dialysis patients has been associated with increased left ventricular mass (LVM), hypertension [...]

Background Atypical hemolytic uremic syndrome (aHUS) evolves into end-stage renal failure in nearly half of affected patients and is associated with defective regulation of the alternative complement pathway. Patients with a complement factor H (CFH) mutation have a 30-100% risk of graft loss due to aHUS recurrence or graft thrombosis. Since CFH is produced predominantly by the liver, combined liver-kidney transplant is a curative treatment option. One major unexpected risk includes liver failure secondary to uncontrolled complement activation. We report a successful combined liver-kidney transplantation with perioperative plasma exchange and use of the humanized anti-C5 monoclonal antibody eculizumab. Case Diagnosis/Treatment An 11 -month-old female presented with oliguric renal failure after 3 weeks of flu-like symptoms in the absence of diarrhea. Following the identification of Escherichia coli 0157:H7 in her stool, she was discharged home on peritoneal dialysis with a diagnosis of Shiga toxin-associated HUS. Three months later, she developed severe anemia, thrombocytopenia, and neurological involvement. aHUS was diagnosed and confirmed, and genetic testing revealed a mutation in CFH SCR20. Once donor organs became available, she received preoperative plasma exchange followed by eculizumab infusion with intra-operative fresh frozen plasma prior to combined liver-kidney transplant. At 19 months post-transplant, she continues to have excellent allograft and liver function without signs of disease recurrence. Conclusion Perioperative use of eculizumab in conjunction with plasma exchange during simultaneous liver-kidney transplant can be used to inhibit terminal complement activity, thereby optimizing successful transplantation by reducing the risk of graft thrombosis. Keywords Atypical HUS * Eculizumab * Combined liver kidney transplant * Factor H mutation * Plasma exchange, Case report An 11-month-old African American female presented with a 3-week history of rhinorrhea, cough, intermittent fevers, and emesis without diarrhea. During evaluation, she was hypertensive, in oliguric renal failure [...]

Background: COVID‐19 vaccination has been successful in decreasing rates of SARS‐CoV‐2 infection in areas with high vaccine uptake. Cases of breakthrough SARS‐CoV‐2 infection remain infrequent among immunocompetent vaccine recipients who are protected from severe COVID‐19. Robust data demonstrate the safety, immunogenicity, and effectiveness of several COVID‐19 vaccine formulations. Importantly, Pfizer‐BioNTech BNT162b2 mRNA COVID‐19 vaccine studies have now included children as young as 5 years of age with safety, immunogenicity, and effectiveness data publicly available. In the United States, emergency use authorization by the Federal Drug Administration and approval from the Centers for Disease Control/Advisory Committee on Immunization Practices have been provided for the 5‐ to 11‐year‐old age group. Methods: Members of the International Pediatric Transplant Association (IPTA) provide an updated review of current COVID‐19 vaccine data with focus on pediatric solid organ transplant (SOT)‐specific issues. Results: This review provides an overview of current COVID‐19 immunogenicity, safety, and efficacy data from key studies, with focus on data of importance to pediatric SOT recipients. Continued paucity of data in the setting of pediatric transplantation remains a challenge. Conclusions: Further studies of COVID‐19 vaccination in pediatric SOT recipients are needed to better understand post‐vaccine COVID‐19 T‐cell and antibody kinetics and determine the optimal vaccine schedule. Increased COVID‐19 vaccine acceptability, uptake, and worldwide availability are needed to limit the risk that COVID‐19 poses to pediatric solid organ transplant recipients. [ABSTRACT FROM AUTHOR]

Pediatric hypertension (HTN) is a growing concern and should be diagnosed and treated aggressively to reduce the global disease burden. Ambulatory blood pressure monitoring (ABPM) is a useful clinical tool providing a more accurate description of the patient's blood pressure (BP) than office BP measurements, and can be considered the 'gold standard' in the evaluation of the pediatric patient with a concern for HTN. The American Heart Association have suggested criteria for diagnosing ambulatory HTN, and research continues into further clarification of how to best utilize the large volume of data obtained from an ABPM report. ABPM has some limitations; however, the advantages far outweigh these. Routine use of ABPM is recommended among clinicians to better evaluate and assess the severity of a child's HTN, and for proper management in order to prevent target organ damage and the resulting squeal, thereby reducing the burden of cardiovascular risk in hypertensive children and adolescents. Keywords ABPM * Pediatric hypertension * Ambulatory blood pressure monitoring, The epidemic of obesity along with hypertension (HTN) and cardiovascular disease is a major growing contributor to global disease burden [1, 2]. The prevalence of HTN and pre-HTN in children [...]

Focal segmental glomerulosclerosis (FSGS) is a cause of proteinuric kidney disease, compromising both native and transplanted kidneys. Treatment is limited because of a complex pathogenesis, including unknown serum factors. Here we report that serum soluble urokinase receptor (suPAR) is elevated in two-thirds of subjects with primary FSGS, but not in people with other glomerular diseases. We further find that a higher concentration of suPAR before transplantation underlies an increased risk for recurrence of FSGS after transplantation. Using three mouse models, we explore the effects of suPAR on kidney function and morphology. We show that circulating suPAR activates podocyte [β.sub.3] integrin in both native and grafted kidneys, causing foot process effacement, proteinuria and FSGS-like glomerulopathy. Our findings suggest that the renal disease only develops when suPAR sufficiently activates podocyte [β.sub.3] integrin. Thus, the disease can be abrogated by lowering serum suPAR concentrations through plasmapheresis, or by interfering with the suPAR-[β.sub.3] integrin interaction through antibodies and small molecules targeting either uPAR or [β.sub.3] integrin. Our study identifies serum suPAR as a circulating factor that may cause FSGS., Focal segmental glomerulosclerosis (FSGS) is a major cause of endstage renal disease (ESRD) (1). It affects both native and transplanted kidneys (2-4), with recurrence after transplant occurring in about 30% [...]

Background: Population‐level COVID‐19 immunization will play a key role in slowing down the SARS‐CoV‐2 pandemic on a global scale and protect the most at‐risk individuals. Thanks to a formidable universal effort, several SARS‐CoV‐2 vaccines have been marketed less than a year since the first documented COVID‐19 case, with promising safety, efficacy, and immunogenicity results in adults. As children were not included in the initial trials, no vaccine is currently approved for individuals <16 years of age. Similarly, immunosuppressed individuals, such as solid organ transplant recipients, were excluded from initial vaccine trials, limiting the understanding of vaccine immunogenicity and safety in this at‐risk population. Thus, data regarding COVID‐19 vaccination in pediatric solid organ transplantation recipients are currently lacking. Methods: Members of the International Pediatric Transplant Association review the current general status of COVID‐19 vaccines focusing on pediatric‐specific issues. Results: This review provides an overview of COVID‐19 vaccines in pediatric SOT recipients and highlights the current paucity of data in both pediatric and transplant settings in terms of safety, immunogenicity, and clinical efficacy. Conclusions: Vaccine trials including children and transplant recipients are underway and will be necessary to characterize COVID‐19 vaccine safety, immunogenicity, and efficacy, which will determine potential future research directions. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has proven to be a challenge in regard to the clinical presentation, prevention, diagnosis, and management of SARS‐CoV‐2 infection among children who are candidates for and recipients of SOT. By providing scenarios and frequently asked questions encountered in routine clinical practice, this document provides expert opinion and summarizes the available data regarding the prevention, diagnosis, and management of SARS‐CoV‐2 infection among pediatric SOT candidates and recipients and highlights ongoing knowledge gaps requiring further study. Currently available data are still lacking in the pediatric SOT population, but data have emerged in both the adult SOT and general pediatric population regarding the approach to COVID‐19. The document provides expert opinion regarding prevention, diagnosis, and management of SARS‐CoV‐2 infection among pediatric SOT candidates and recipients. [ABSTRACT FROM AUTHOR]

Diarrhea in the pediatric solid organ transplantation (SOT) recipient is a frequent complaint that is associated with significant morbidity and impaired quality of life. There are limited published data regarding the specific epidemiology, diagnostic evaluation, and treatment of diarrhea after SOT in children. Pediatric SOT recipients have an increased risk of developing diarrhea because of a generalized immunosuppressed state, epidemiologic exposures, and polypharmacy. There is a need to standardize the diagnostic evaluation of diarrhea in children after SOT to facilitate an accurate diagnosis and timely treatment. Herein, we review the available published data and propose a systematic, stepwise approach to the evaluation of diarrhea in this high‐risk population, focusing on timely diagnosis of both infectious and non‐infectious causes, in order to provide focused management. Prospective studies are needed to better assess the true prevalence, risk factors for, etiologies, and complications of diarrhea in pediatric SOT patients that will guide optimal management. Development of effective vaccines and antiviral therapies for enteric viruses may also contribute to improved outcomes. [ABSTRACT FROM AUTHOR]