Acute kidney injury among pediatric COVID-19 patients admitted to the ICU in North America

By Tarun Sai LomteReviewed by Danielle Ellis, B.Sc.Apr 28 2022

In a recent study published in PLoS ONE, researchers analyzed acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) pediatric patients.

Background

Kidney-related complications due to COVID-19 have become prevalent, with AKI accounting for higher mortality rates. In a previous meta-analysis, researchers of the present study evaluated the incidence and outcomes of AKI among adult and pediatric COVID-19 cases. More than 30% of pediatric COVID-19 patients developed AKI than 15.9% of adult COVID-19 patients. Overall, they observed a 2.55% mortality rate in children and 14.6% in adults.

Despite the age discrepancy, renal association with COVID-19 has been an adverse prognostic factor. While several research groups have been studying AKI epidemiology in pediatric COVID-19 cases reporting varying incidence rates, a large-scale, pan-North America assessment has not been carried out.

About the study

In this retrospective study, researchers analyzed COVID-19 cases in the pediatric population (aged 21 years or lower) requiring intensive care (ICU) across North America using the virtual pediatric systems (VPS) database. Pediatric patients with AKI and those with a current or previous history of COVID-19 were analyzed. COVID-19 patients were identified using the International Classification of Diseases tenth revision (ICD-10).

The team investigated the epidemiology, risk factors of AKI, treatment results, and mortality. The following variables were utilized: patient demographics, diagnosis, laboratory results, imaging results, respiratory support modality, medications, kidney replacement therapy (KRT) modality, interventions and procedures, discharge status, pediatric index of mortality 2 (PIM2), and PIM3, length of stay (LOS).

Patients were categorized into AKI and non-AKI groups. AKI group patients were further classified based on the severity stage of AKI per kidney disease, improving global outcomes (KDIGO) guidelines. Continuous outcome variables were hospital LOS, PIM2 probability of death, and PIM3 probability of death. Categorical variables were mortality, respiratory and airway support, kidney support, cardiovascular support, and vascular access. Continuous variables were summarized as inter-quartile ranges (IQR) and medians, while categorical variables were represented as percentages and frequencies.

Each variable was tested for normality by the Kolmogorov-Smirnov test. Mann-Whitney U test for continuous variables and Fischer exact or chi-squared test for categorical variables were performed as univariate analyses to examine the unadjusted relationship between variables or different outcomes. Significant variables in the univariate analysis were subject to multivariate linear or logistic regression analysis after adjustment.

Findings

Among the 2546 COVID-19-positive pediatric cases as of July 2021, 274 (10.8%) had AKI. Of these, 62 patients were diagnosed with stage 3 AKI, and 40 others had stage 2 AKI. The median age of AKI patients (5 years) was significantly higher than those without AKI (4 years). There was no statistical significance in gender, ethnicity, race, baseline pediatric overall performance, and baseline pediatric cerebral performance category between the two groups.

Comorbidities such as respiratory, endocrinal, cardiovascular, and hematologic dysfunctions were significantly higher in those with AKI than in non-AKI patients. Many laboratory parameters were higher among AKI patients: serum potassium and glucose, creatinine, leucocyte count, blood urea nitrogen, and estimated glomerular filtration rate (eGFR). Bicarbonate levels and pH were significantly lower in the AKI cohort than in the non-AKI cohort.

Both categorical and continuous outcome variables were significantly higher in the AKI subset than in the non-AKI cohort. For instance, in the univariate analysis, hospital LOS was 9.04 days for the AKI cohort compared to 5.09 days for the non-AKI group. PIM2 and PIM3 probability of death was 1.2% and 0.98% in the AKI group, respectively, compared to 0.96% and 0.78% in the non-AKI cohort. For continuous variables, the crude odds ratios (ORs) were 5.01 for mortality, 1.63 for respiratory and airway support, 3.57 for cardiorespiratory support, 12.52 for kidney support, and 4.84 for vascular access.

Even after adjustment, the categorical and continuous outcome variables were greater in AKI patients than in non-AKI cases. Adjusted ORs were 1.61 (respiratory and airway support), 2.69 (mortality), 3.51 (vascular access), and 5.34 (kidney support). When continuous or categorical outcomes were compared to different AKI stages, statistically significant results were obtained for hospital LOS, airway and respiratory support, and vascular access but not for PIM2 or PIM3 probability of death.

Conclusions

The study observed a higher incidence of AKI among pediatric COVID-19 patients in ICUs than previously reported by multiple studies. Moreover, mortality rates were higher among patients in the AKI group.

Given the retrospective nature of the study, a few limitations exist. Notably, the results presented here are representative of North America only from select pediatric ICUs in the region and could not be applied globally. Notwithstanding the lower risk of severe COVID-19 in children, it is critical to continue to build the knowledge base of COVID-19-related manifestations in children. A better understanding of the disease could potentially address the increased morbidity and mortality rates in the future.