EVALUATING EPIDEMIOLOGICAL RISK FACTORS FOR PEDIATRIC ACUTE KIDNEY INJURY GLOBALLY: FROM THE UNITED STATES AND A LOW-RESOURCED SETTING IN MALAWI

Background: Acute kidney injury (AKI) can be fatal if unrecognized. This work aimed to evaluate pediatric AKI epidemiology in two distinct hospital settings—a United States database and a prospective cohort of Malawian trauma patients. Many African hospitals are hampered by limited AKI diagnostics. So, we validated a novel AKI dipstick (NGALds®) that relies on minimal resources. Methods: The U.S. evaluation of hospitalized children used the Kids’ Inpatient Database (nationally-representative sample of pediatric discharges). Linear regression models looked at sociodemographic risk factors associated with AKI. In Malawi, we prospectively evaluated AKI amongst trauma patients. We evaluated several AKI definitions to optimize baseline creatinine estimation, which is not standardized. We calculated univariate relative risks (RR) for hypothesis-generation of potential risk factors associated with AKI in trauma patients. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) evaluated the validity of the NGALds® to diagnose AKI. Results: In the U.S., AKI occurred in approximately 12.3/1000 pediatric hospitalizations, which translates to almost 30,000 children nationally. Uninsured children were more likely to suffer AKI compared to children with Medicaid (adjusted risk difference 14/1000 hospitalizations, 95% confidence interval (CI) 12-16). In Malawi, depending on baseline creatinine definition, AKI incidence ranged from 4-10%. Almost one in ten children died, but those with AKI were at significantly higher risk of death compared to those without AKI (RR 6.5, 95% CI 2.2-19.1). The NGALds® had sensitivity 44.4%, specificity 73.5%, PPV 19.5%, and NPV 90.2% for predicting AKI. AKI was associated with an increased risk of mortality (RR 3.9, 95% CI 1.9-8.2), but it was greatly increased amongst children who first had a positive (≥150ng/mL) NGALds® (RR 12.0, 95% CI 1.8-78.4). Conclusion: In the US, we identified that lack of insurance was a key risk factor for AKI. In the first analysis of AKI in African pediatric trauma patients, we showed that AKI significantly increases mortality risk. More promising is the validation we conducted of a novel dipstick for point-of-care identification and risk stratification of AKI amongst trauma patients. This dipstick may drastically improve our AKI epidemiological studies and clinical care algorithms, saving lives throughout Africa.Doctor of Philosoph

Saliva urea nitrogen dipsticks to predict acute kidney injury in Malawian trauma patients

Background: Many low-resource settings have limited access to serum creatinine tests necessary for kidney disease identification. Among Malawian patients who are hospitalized after trauma, we evaluated the use of point-of-care saliva urea nitrogen (SUN) dipsticks to predict acute kidney injury (AKI). Methods: In a nested prospective cohort study, we enrolled hospitalized acute trauma patients aged ≥6 months to evaluate AKI (defined by KDIGO criteria) and the test characteristics of SUN to predict AKI. Results: Among 335 participants (approximately three-quarters able to expectorate and 34% aged ≤18 years), 12.5% (n = 42) developed AKI. At a SUN threshold of ≥40 mg/dL, a positive dipstick test was specific (99.3%) but insensitive (14.3%) in predicting AKI, with a positive predictive value of 75% and negative predictive value of 89%. At this threshold, 2.4% of participants were dipstick-positive (SUN+), and 75% of those had AKI. Reducing the SUN threshold to ≥30 mg/dL increased participants who were SUN+ to 5.0% (n = 16) but also increased the false positive rate and missed 79% (n = 33) of AKI cases. Stratified results showed better performance among adults than children and similar results when comparing participants who could and could not expectorate. There was moderate correlation between categorized BUN values and SUN (r = 0.53) but less agreement (weighted kappa 0.27; 95% CI 0.17–0.37). Conclusions: SUN dipstick testing has good specificity and negative predictive value for ruling out AKI, but poor sensitivity. We found similar results among those who could or could not expectorate a saliva sample

Determining the quality of IMCI pneumonia care in Malawian children

Although pneumonia is the leading cause of child mortality worldwide, little is known about the quality of routine pneumonia care in high burden settings like Malawi that utilize World Health Organization’s Integrated Management of Childhood Illnesses (IMCI) guidelines. Due to severe human resource constraints, the majority of clinical care in Malawi is delivered by non-physician clinicians called Clinical Officers (COs)

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

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.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

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 COVID19: 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: 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

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 \u3c 0.01), Black (35.6% vs 21.9%; p \u3c 0.01), present with fever/abdominal pain than cough/dyspnea (p \u3c 0.01), and less likely to have comorbidities (33.3% vs 61.9%; p \u3c 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 \u3c 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 \u3c 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 \u3c 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 \u3c 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

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 \u3c 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

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 \u3e75th 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