Fluid assessment, fluid balance, and fluid overload in sick children: a report from the Pediatric Acute Disease Quality Initiative (ADQI) conference.

BACKGROUND: The impact of disorders of fluid balance, including the pathologic state of fluid overload in sick children has become increasingly apparent. With this understanding, there has been a shift from application of absolute thresholds of fluid accumulation to an appreciation of the intricacies of fluid balance, including the impact of timing, trajectory, and disease pathophysiology. METHODS: The 26th Acute Disease Quality Initiative was the first to be exclusively dedicated to pediatric and neonatal acute kidney injury (pADQI). As part of the consensus panel, a multidisciplinary working group dedicated to fluid balance, fluid accumulation, and fluid overload was created. Through a search, review, and appraisal of the literature, summative consensus statements, along with identification of knowledge gaps and recommendations for clinical practice and research were developed. CONCLUSIONS: The 26th pADQI conference proposed harmonized terminology for fluid balance and for describing a pathologic state of fluid overload for clinical practice and research. Recommendations include that the terms daily fluid balance, cumulative fluid balance, and percent cumulative fluid balance be utilized to describe the fluid status of sick children. The term fluid overload is to be preserved for describing a pathologic state of positive fluid balance associated with adverse events. Several recommendations for research were proposed including focused validation of the definition of fluid balance, fluid overload, and proposed methodologic approaches and endpoints for clinical trials.

Pediatric AKI in the real world: changing outcomes through education and advocacy-a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

BACKGROUND: Acute kidney injury (AKI) is independently associated with increased morbidity and mortality across the life course, yet care for AKI remains mostly supportive. Raising awareness of this life-threatening clinical syndrome through education and advocacy efforts is the key to improving patient outcomes. Here, we describe the unique roles education and advocacy play in the care of children with AKI, discuss the importance of customizing educational outreach efforts to individual groups and contexts, and highlight the opportunities created through innovations and partnerships to optimize lifelong health outcomes. METHODS: During the 26th Acute Disease Quality Initiative (ADQI) consensus conference, a multidisciplinary group of experts discussed the evidence and used a modified Delphi process to achieve consensus on recommendations on AKI research, education, practice, and advocacy in children. RESULTS: The consensus statements developed in response to three critical questions about the role of education and advocacy in pediatric AKI care are presented here along with a summary of available evidence and recommendations for both clinical care and research. CONCLUSIONS: These consensus statements emphasize that high-quality care for patients with AKI begins in the community with education and awareness campaigns to identify those at risk for AKI. Education is the key across all healthcare and non-healthcare settings to enhance early diagnosis and develop mitigation strategies, thereby improving outcomes for children with AKI. Strong advocacy efforts are essential for implementing these programs and building critical collaborations across all stakeholders and settings.

Adolescent Kidney Outcomes after Extremely Preterm Birth and Neonatal Acute Kidney Injury: There May be More to the Story.

OBJECTIVE: Among children born extremely preterm (EP), the antecedents of chronic kidney disease (CKD), including neonatal acute kidney injury (nAKI), are not well characterized. STUDY DESIGN: This was a retrospective cohort pilot study. Participants (n = 36) were adolescents born before 28 weeks of gestation enrolled at birth into the extremely low gestational age newborn study, between 2002 and 2004, at the University of North Carolina. Participants were stratified by the primary exposure to nAKI, defined using the modified Kidney Disease Improving Global Outcomes nAKI criteria. Baseline serum creatinine (SCr) was defined as the lowest SCr after 48 to 72 postnatal hours. The primary outcome was an abnormal kidney profile during adolescence, defined as having one or more of these outcomes: elevated blood pressure (>120/80 mm Hg), microalbuminuria (urine microalbumin/creatinine >30 µg/g), or an abnormal kidney volume measured by ultrasound (total kidney volume corrected for body surface area <10th%ile for age). RESULTS: Half of the participants had a history of nAKI. Thirteen had stage 1 nAKI, four had stage 2, and one had stage 3 nAKI. At 15 years of age, 50% were overweight/obese, 31% had elevated blood pressure (BP), 11% had abnormal kidney volumes, and 17% had microalbuminuria. The relative risk for having an abnormal kidney profile during adolescence among participants with a history of nAKI was 0.63 (95% confidence interval: 0.3-1.3, p = 0.2). CONCLUSION: In this sample of adolescents born EP, a history of nAKI was not associated with elevated BP, microalbuminuria, or abnormal kidney volume. Future studies are needed in larger samples to better characterize the relationship between nAKI and CKD in EP-born children. KEY POINTS: · Extremely preterm birth is associated with acute kidney injury.. · Extremely preterm birth is associated with chronic kidney disease.. · Neonatal acute kidney injury after extremely preterm birth was not associated with kidney outcomes..

Characterization and Outcomes of Hospitalized Children With Coronavirus Disease 2019: A Report From a Multicenter, Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry.

OBJECTIVES: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry. DESIGN: Retrospective study. SETTING: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry. PATIENTS: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25-14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16-25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2-7.7 d) and 4 days (1.9-7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased. CONCLUSIONS: In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.

Acute kidney injury in critically Ill children and young adults with suspected SARS-CoV2 infection.

BACKGROUND: We aimed to study the association of suspected versus confirmed infection with the novel SARS-CoV2 virus with the prevalence of acute kidney injury (AKI) in critically ill children. METHODS: Sequential point-prevalence study of children and young adults aged 7 days to 25 years admitted to intensive care units under investigation for SARS-CoV2 infection. AKI was staged in the first 14 days of enrollment using KDIGO creatinine-based staging. SARS-CoV2 positive (CONFIRMED) were compared to SUSPECTED (negative or unknown). Outcome data was censored at 28-days. RESULTS: In 331 patients of both sexes, 179 (54.1%) were CONFIRMED, 4.2% (14) died. AKI occurred in 124 (37.5%) and severe AKI occurred in 63 (19.0%). Incidence of AKI in CONFIRMED was 74/179 (41.3%) versus 50/152 (32.9%) for SUSPECTED; severe AKI occurred in 35 (19.6%) of CONFIRMED and 28 (18.4%) of SUSPECTED. Mortality was 6.2% (n = 11) in CONFIRMED, but 9.5% (n = 7) in those CONFIRMED with AKI. On multivariable analysis, only Hispanic ethnicity (relative risk 0.5, 95% CI 0.3-0.9) was associated with less AKI development among those CONFIRMED. CONCLUSIONS: AKI and severe AKI occur commonly in critically ill children with SARS-CoV2 infection, more than double the historical standard. Further investigation is needed during this continuing pandemic to describe and refine the understanding of pediatric AKI epidemiology and outcomes. TRIAL REGISTRATION: NCT01987921. IMPACT: What is the key message of the article? AKI occurs in children exposed to the novel SARS-CoV2 virus at high prevalence (~40% with some form of AKI and 20% with severe AKI). What does it add to the existing literature? Acute kidney injury (AKI) occurs commonly in adult patients with SARS-CoV2 (COVID), very little data describes the epidemiology of AKI in children exposed to the virus. What is the impact? A pediatric vaccine is not available; thus, the pandemic is not over for children. Pediatricians will need to manage significant end-organ ramifications of the novel SARS-CoV2 virus including AKI.

Fluid balance in pediatric critically ill patients (with and without kidney dysfunction).

PURPOSE OF REVIEW: The issues of fluid balance and fluid overload are currently considered crucial aspects of pediatric critically ill patients' care. RECENT FINDINGS: This review describes current understanding of fluid management in critically ill children in terms of fluid balance and fluid overload and its effects on patients' outcomes. The review describes current evidence surrounding definitions, monitoring, and treatment of positive fluid balance. In particular, the review focuses on specific patient conditions, including perioperative cardiac surgery, severe acute respiratory failure, and extracorporeal membrane oxygenation therapy, as the ones at highest risk of developing fluid overload and poor clinical outcomes. Gaps in understanding include specific thresholds at which fluid overload occurs in all critically ill children or specific populations and optimal timing of decongestion of positive fluid balance. SUMMARY: Current evidence on fluid balance in critically ill children is mainly based on retrospective and observational studies, and intense research should be recommended in this important field. In theory, active decongestion of patients with fluid overload could improve mortality and other clinical outcomes, but randomized trials or advanced pragmatic studies are needed to better understand the optimal timing, patient characteristics, and tools to achieve this.

Kidney implications of SARS-CoV2 infection in children.

Research indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection can impact every organ, and the effects can range from asymptomatic to severe disease. Since it was first discovered in December 2019, our understanding has grown about its impact on kidney disease. In general, children have less severe disease than adults, and this tendency appears to extend to special pediatric kidney populations (e.g., chronic kidney disease and immunosuppressed patients with solid organ transplants or nephrotic syndrome). However, in a fraction of infected children, SARS-CoV2 causes an array of kidney manifestations, ranging from acute kidney injury to thrombotic microangiopathy, with potential implications for increased risk of morbidity and mortality. Additional considerations surround the propensity for clotting extracorporeal circuits in children with SARS-CoV2 infection that are receiving kidney replacement therapy. This review provides an update on our current understanding of SARS-CoV2 for pediatric nephrologists and highlights knowledge gaps to be addressed by future research during this ongoing pandemic, particularly the social disparities magnified during this period.

Derivation and evaluation of baseline creatinine equations for hospitalized children and adolescents: the AKI baseline creatinine equation.

BACKGROUND: Acute kidney injury (AKI) definitions incorporate baseline creatinine (Crb) values, but Crb are frequently unknown in pediatrics. Our primary aim was to derive and validate a novel AKI Baseline Creatinine (ABC) estimation equation and compare it to existing methods of estimating Crb values. METHODS: We conducted a single-center retrospective analysis of pediatric patients (0-25 years) admitted from 2012 to 2019. Included patients required at least one outpatient Crb prior to hospitalization (gold standard). Novel equations were developed with demographic and initial creatinine data. Existing methods included back-calculating Crb based on Schwartz, Full Age Spectrum (FAS), and CKiD-under-25 (U25) equations. To determine an optimal equation, we compared novel and existing equations to the gold standard. RESULTS: The optimal simplified equation (ABC) included only age and had R2 = 59.9% and 73.2% of values within 30% of true Crb. The precision increased significantly when the equation included age and minimum creatinine within initial 72 h (ABC-cr): R2 = 75.4% and 86.5% of values within 30% of true Crb. The best performing existing equation was the age-based FAS, which had R2 = 61.0% and 78.0% of values within 30% of true Crb. All other existing equations performed worse, some methods as low as 52.6% within 30% of true Crb. CONCLUSIONS: The newly derived ABC equation is simple, and the ABC-cr equation can more accurately estimate Crb by ≥ 25% compared to previous methods. The potential applicability of these equations is vast, including faster recognition of AKI on initial patient contact and improved standardization of pediatric AKI definitions, enhancing health services research. A higher resolution version of the Graphical abstract is available as Supplementary information.

SARS-CoV-2 infection increases risk of acute kidney injury in a bimodal age distribution.

BACKGROUND: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern. METHODS: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators. RESULTS: Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds. CONCLUSIONS: SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.

SARS-CoV-2 With Concurrent Respiratory Viral Infection as a Risk Factor for a Higher Level of Care in Hospitalized Pediatric Patients.

OBJECTIVE: As of early 2021, there have been over 3.5 million pediatric cases of SARS-CoV-2, including 292 pediatric deaths in the United States. Although most pediatric patients present with mild disease, they are still at risk for developing significant morbidity requiring hospitalization and intensive care unit (ICU) level of care. This study was performed to evaluate if the presence of concurrent respiratory viral infections in pediatric patients admitted to the hospital with SARS-CoV-2 was associated with an increased rate of ICU level of care. DESIGN: A multicenter, international, noninterventional, cross-sectional study using data provided through The Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study database. SETTING: The medical ward and ICU of 67 participating hospitals. PATIENTS: Pediatric patients younger than 18 years hospitalized with SARS-CoV-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 922 patients were included. Among these patients, 391 required ICU level care and 31 had concurrent non-SARS-CoV-2 viral coinfection. In a multivariate analysis, after accounting for age, positive blood culture, positive sputum culture, preexisting chronic medical conditions, the presence of a viral respiratory coinfection was associated with need for ICU care (odds ratio, 3.6; 95% confidence interval, 1.6-9.4; P < 0.01). CONCLUSIONS: This study demonstrates an association between concurrent SARS-CoV-2 infection with viral respiratory coinfection and the need for ICU care. Further research is needed to identify other risk factors that can be used to derive and validate a risk-stratification tool for disease severity in pediatric patients with SARS-CoV-2.

Coronavirus Disease 2019-Associated PICU Admissions: A Report From the Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study Registry.

OBJECTIVES: To compare clinical characteristics and outcomes of children admitted to the PICU for severe acute respiratory syndrome coronavirus 2-related illness with or without multisystem inflammatory syndrome in children. The secondary objective was to identify explanatory factors associated with outcome of critical illness defined by a composite index of in-hospital mortality and organ system support requirement. DESIGN: Retrospective cohort study. SETTING: Thirty-eight PICUs within the Viral Infection and Respiratory Illness Universal Study registry from March 2020 to January 2021. PATIENTS: Children less than 18 years with severe acute respiratory syndrome coronavirus 2-related illness with or without multisystem inflammatory syndrome in children. MEASUREMENTS AND MAIN RESULTS: Of 394 patients, 171 (43.4%) had multisystem inflammatory syndrome in children. Children with multisystem inflammatory syndrome in children were more likely younger (2-12 yr vs adolescents; p < 0.01), Black (35.6% vs 21.9%; p < 0.01), present with fever/abdominal pain than cough/dyspnea (p < 0.01), and less likely to have comorbidities (33.3% vs 61.9%; p < 0.01) compared with those without multisystem inflammatory syndrome in children. Inflammatory marker levels, use of inotropes/vasopressors, corticosteroids, and anticoagulants were higher in multisystem inflammatory syndrome in children patients (p < 0.01). Overall mortality was 3.8% (15/394), with no difference in the two groups. Diagnosis of multisystem inflammatory syndrome in children was associated with longer duration of hospitalization as compared to nonmultisystem inflammatory syndrome in children (7.5 d[interquartile range, 5-11] vs 5.3 d [interquartile range, 3-11 d]; p < 0.01). Critical illness occurred in 164 patients (41.6%) and was more common in patients with multisystem inflammatory syndrome in children compared with those without (55.6% vs 30.9%; p < 0.01). Multivariable analysis failed to show an association between critical illness and age, race, sex, greater than or equal to three signs and symptoms, or greater than or equal to two comorbidities among the multisystem inflammatory syndrome in children cohort. Among nonmultisystem inflammatory syndrome in children patients, the presence of greater than or equal to two comorbidities was associated with greater odds of critical illness (odds ratio 2.95 [95% CI, 1.61-5.40]; p < 0.01). CONCLUSIONS: This study delineates significant clinically relevant differences in presentation, explanatory factors, and outcomes among children admitted to PICU with severe acute respiratory syndrome coronavirus 2-related illness stratified by multisystem inflammatory syndrome in children.

High risk of acute kidney injury in Malawian trauma patients: a prospective observational cohort study.

BACKGROUND: Trauma is a common cause of acute kidney injury (AKI). Yet little data exist regarding trauma-related-AKI in low-resourced settings, where the majority of deaths from AKI and trauma occur. We prospectively evaluated epidemiology of AKI in hospitalized Malawian trauma patients. METHODS: AKI was defined by creatinine-only Kidney Disease Improving Global Outcomes (KDIGO) criteria. Those with AKI were followed up 3-6 months later to determine persistent kidney abnormalities. We calculated univariate statistics with Wilcoxon rank sum tests, Fisher's exact, and chi-square tests to compare those with and without AKI. Multivariate log-risk regression modelling was used to determine risk ratios (RR) and 95% confidence intervals (CI) for AKI development. RESULTS: Of 223 participants, 14.4% (n = 32) developed AKI. Most patients were young (median age 32) males (n = 193, 86.5%) involved in road traffic injuries (n = 120, 53.8%). After adjusting for confounders, those with severe anemia during their admission were 1.4 times (RR 1.4, 95% CI 1.1-1.8) more likely to develop AKI than those without. Overall mortality was 7.6% (n = 17), and those who developed AKI were more likely to die than those who did not (18.8% vs 5.6%, p-value = 0.02). Almost half of those with AKI (n = 32) either died (n = 6) or had persistent kidney dysfunction at follow-up (n = 8). CONCLUSION: In one of the few African studies on trauma-related AKI, we found a high incidence of AKI (14.4%) in Malawian trauma patients with associated poor outcomes. Given AKI's association with increased mortality and potential ramifications on long-term morbidity, urgent attention is needed to improve AKI-related outcomes.

Racial and health insurance disparities in pediatric acute kidney injury in the USA.

BACKGROUND: Acute kidney injury (AKI) significantly increases morbidity and mortality for hospitalized children, yet sociodemographic risk factors for pediatric AKI are poorly described. We examined sociodemographic differences in pediatric AKI amongst a national cohort of hospitalized children. METHODS: Secondary analysis of the most recent (2012) Kids' Inpatient Database (KID) from the Agency for Healthcare Research and Quality. Study sample weights were used to obtain national estimates of AKI (defined by administrative data). KID is a nationally representative sample of pediatric discharges throughout the USA. Linear risk regression models were used to assess the relationship between our primary exposures (race/ethnicity, health insurance, household urbanization, gender, and age) and the diagnosis of AKI, adjusting for comorbidities. RESULTS: A total of 1,699,841 hospitalizations met our study criteria. In 2012, AKI occurred in approximately 12.3/1000 pediatric hospitalizations, which translates to almost 30,000 children nationally. Asian/Pacific Islander, African-American, and Hispanic children were at slightly increased risk for AKI compared to Caucasian children (adjusted risk difference (RD) 4.5 per 1000 hospitalizations, 95% confidence interval (CI) 2.9-6.0; 2.5/1000 hospitalizations, 95% CI 1.7-3.3; and 1.7/1000 hospitalizations, 95% CI 0.9-2.5, respectively). Uninsured children were more likely to suffer AKI compared to children with any health insurance (e.g., no insurance versus Medicaid: adjusted RD 14.4/1000 hospitalizations, 95% CI 12.7-16.2). Based on these national estimates, one episode of AKI might be prevented if 70 (95% CI 62-79) hospitalized children without insurance were provided with Medicaid. CONCLUSIONS: Pediatric AKI occurs more frequently in racial minority and uninsured children, factors linked to lower socioeconomic status.

Incidence and epidemiology of acute kidney injury in a pediatric Malawian trauma cohort: a prospective observational study.

BACKGROUND: Acute kidney injury (AKI) is highly associated with mortality risk in children worldwide. Trauma can lead to AKI and is a leading cause of pediatric death in Africa. However, there is no information regarding the epidemiology of pediatric, trauma-associated AKI in Africa. METHODS: Prospective cohort study of pediatric trauma patients admitted to a tertiary referral hospital in Malawi. Participants enrolled at admission were followed prospectively throughout their hospitalization. AKI was defined by creatinine-only Kidney Disease Improving Global Outcomes criteria. We calculated descriptive statistics and univariate relative risks (RR) for hypothesis-generation of potential risk factors associated with AKI. RESULTS: We analyzed data from 114 participants. Depending on baseline creatinine definition, AKI incidence ranged from 4 to 10%. The new Schwartz equation estimated baseline creatinine values best and yielded an AKI incidence of 9.7%. Almost one in ten children died during hospitalization, but those with AKI (n = 4) were at significantly higher risk of death compared to those without AKI (40.0% vs 6.2%; RR 6.5, 95% CI 2.2-19.1). Burn injuries were most commonly associated with AKI (63.6%). Other potential AKI risk factors included multiple injuries, trunk or facial injuries, and recent consumption of herbal remedies. CONCLUSIONS: AKI occurs in up to 10% of admitted pediatric trauma patients in Malawi and increases the risk of death 7-fold compared to those without AKI. This large unrecognized burden in trauma requires further investment by researchers, clinicians and policymakers to develop evidenced-based triage, recognition, and management approaches to prevent the associated sequelae and potential mortality from AKI.

Structures, Organization, and Delivery of Kidney Care to Children Living in Low-Resource Settings.

Introduction: There is a disparity in the availability of health care for children in resource-constrained countries. The International Pediatric Nephrology Association (IPNA) commissioned an initiative exploring the challenges in the care of children with kidney disease in low- or middle-income countries (LMICs) with a focus on human, diagnostic, and therapeutic resources. Methods: A survey was sent by e-mail to all members of IPNA and its affiliated regional or national societies residing in LMICs. Data were extracted from individual responses after merging duplicate data. Descriptive analysis was done using Microsoft Excel. Results: Responses were obtained from 245 centers across 62 countries representing 88% of the LMIC pediatric population. Regional disparity in the availability of basic diagnostic and therapeutic resources was noted. Even when resources were available, they were not accessible or affordable in 15% to 20% of centers. Acute and chronic dialysis were available in 85% and 75% of centers respectively. Lack of trained nurses, pediatric-specific supplies, and high costs were barriers to providing dialysis in these regions. Kidney transplantation was available in 32% of centers, with the cost of transplantation and lack of surgical expertise reported as barriers. About 65% of centers reported that families with chronic disease opted to discontinue care, with financial burden as the most common reason cited. Conclusion: The survey highlights the existing gaps in workforce, diagnostic, and therapeutic resources for pediatric kidney care in resource-constrained regions. We need to strengthen the health care workforce, address disparities in health care resources and funding, and advocate for equitable access to medications, and kidney replacement therapy (KRT).

Early combination therapy with immunoglobulin and steroids is associated with shorter ICU length of stay in Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19: A retrospective cohort analysis from 28 U.S. Hospitals.

OBJECTIVES: Suggested therapeutic options for Multisystem Inflammatory Syndrome in Children (MIS-C) include intravenous immunoglobulins (IVIG) and steroids. Prior studies have shown the benefit of combination therapy with both agents on fever control or the resolution of organ dysfunction. The primary objective of this study was to analyze the impact of IVIG and steroids on hospital and ICU length of stay (LOS) in patients with MIS-C associated with Coronavirus Disease 2019 (COVID-19). STUDY DESIGN: This was a retrospective study on 356 hospitalized patients with MIS-C from March 2020 to September 2021 (28 sites in the United States) in the Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 Registry. The effect of IVIG and steroids initiated in the first 2 days of admission, alone or in combination, on LOS was analyzed. Adjustment for confounders was made by multivariable mixed regression with a random intercept for the site. RESULTS: The median age of the study population was 8.8 (Interquartile range (IQR) 4.0, 13) years. 247/356 (69%) patients required intensive care unit (ICU) admission during hospitalization. Overall hospital mortality was 2% (7/356). Of the total patients, 153 (43%) received IVIG and steroids, 33 (9%) received IVIG only, 43 (12%) received steroids only, and 127 (36%) received neither within 2 days of admission. After adjustment of confounders, only combination therapy showed a significant decrease of ICU LOS by 1.6 days compared to no therapy (exponentiated coefficient 0.71 [95% confidence interval 0.51, 0.97, p = 0.03]). No significant difference was observed in hospital LOS or the secondary outcome variable of the normalization of inflammatory mediators by Day 3. CONCLUSIONS: Combination therapy with IVIG and steroids initiated in the first 2 days of admission favorably impacts ICU but not the overall hospital LOS in children with MIS-C.

Association of Early Steroid Administration With Outcomes of Children Hospitalized for COVID-19 Without Multisystem Inflammatory Syndrome in Children.

Importance: There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C). Objective: To determine whether the use of steroids within 2 days of admission for non-MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence. Design, Setting, and Participants: This cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non-MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry. Exposure: Administration of steroids within 2 days of admission. Main Outcomes and Measures: Length of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching. Results: A total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score-matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators. Conclusions and Relevance: Steroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

Gastrointestinal Manifestations in Hospitalized Children With Acute SARS-CoV-2 Infection and Multisystem Inflammatory Condition: An Analysis of the VIRUS COVID-19 Registry.

BACKGROUND: Describe the incidence and associated outcomes of gastrointestinal (GI) manifestations of acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in hospitalized children (MIS-C). METHODS: Retrospective review of the Viral Infection and Respiratory Illness Universal Study registry, a prospective observational, multicenter international cohort study of hospitalized children with acute COVID-19 or MIS-C from March 2020 to November 2020. The primary outcome measure was critical COVID-19 illness. Multivariable models were performed to assess for associations of GI involvement with the primary composite outcome in the entire cohort and a subpopulation of patients with MIS-C. Secondary outcomes included prolonged hospital length of stay defined as being >75th percentile and mortality. RESULTS: Of the 789 patients, GI involvement was present in 500 (63.3%). Critical illness occurred in 392 (49.6%), and 18 (2.3%) died. Those with GI involvement were older (median age of 8 yr), and 18.2% had an underlying GI comorbidity. GI symptoms and liver derangements were more common among patients with MIS-C. In the adjusted multivariable models, acute COVID-19 was no associated with the primary or secondary outcomes. Similarly, despite the preponderance of GI involvement in patients with MIS-C, it was also not associated with the primary or secondary outcomes. CONCLUSIONS: GI involvement is common in hospitalized children with acute COVID-19 and MIS-C. GI involvement is not associated with critical illness, hospital length of stay or mortality in acute COVID-19 or MIS-C.

Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children: A Modified Delphi Consensus Statement.

Importance: Increasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge. Objective: To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy. Evidence Review: At the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations. Findings: The meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy. Conclusions and Relevance: Existing evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.