The Impact of COVID-19 on Pediatric Health: The Incidence of Acute Kidney Injury in MIS-C Cases


Since its emergence in late 2019, the coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has unfolded as a global pandemic, casting a long shadow over human health and all facets of life. As the pandemic progressed, the scientific and medical communities have gradually unraveled the complex pathophysiology of COVID-19, its wide-ranging effects, and the spectrum of associated disorders, shedding light on the multifaceted impact of the virus.

Among the various manifestations of COVID-19, a particularly concerning condition has emerged affecting children and adolescents: the Multisystem Inflammatory Syndrome in Children (MIS-C). This condition was first acknowledged in confirmed COVID-19 cases around late April 2020. By December 2020, the Centers for Disease Control and Prevention (CDC) had documented 1,288 cases of MIS-C.

Characterized by persistent fever, elevated markers of inflammation, and evidence of severe illness necessitating hospitalization, MIS-C involves multiple organ systems, including cardiac, gastrointestinal, renal, hematologic, dermatologic, and neurologic systems. Eligibility for a diagnosis of MIS-C requires the patient to be under 21 years of age and to have been exposed to a confirmed or suspected case of COVID-19. The incidence of MIS-C among those infected with SARS-CoV-2 is reported to be approximately 3.16 cases per 10,000 individuals.

A particularly troubling aspect of MIS-C is its association with acute kidney injury (AKI), a serious condition that can affect children infected with SARS-CoV-2. The prevalence of AKI in pediatric patients with SARS-CoV-2 varies widely across studies, with figures in critically ill children reaching as high as 44%. A comprehensive systematic review has indicated a pooled prevalence of AKI in patients with MIS-C of 20%, based on an analysis of 11 studies encompassing 4,947 patients.

The underlying mechanisms of renal dysfunction in SARS-CoV-2 infections are complex and multifaceted. They include factors such as dehydration, reduced cardiac output, a cytokine storm triggering an excessive immune response, direct viral damage to renal tubular cells, and the use of drugs that are toxic to the kidneys. In the context of MIS-C, renal hypoperfusion—a condition in which the kidneys receive inadequate blood flow—is identified as a primary contributor to the development of AKI.

Despite the growing body of research, there remains a significant gap in our understanding of AKI’s incidence, risk factors, impact on mortality, and the need for specialized care, such as kidney replacement therapy (KRT), in children with MIS-C. This gap is especially pronounced in regions where data are scarce, including Egypt. To address this, a retrospective study was conducted to explore for the first time the incidence of AKI, renal pathology, mortality rates, and the necessity for KRT in Egyptian children afflicted with MIS-C related to COVID-19.

The study’s objective was to provide a clearer picture of AKI’s role in the prognosis of MIS-C and to inform future treatment protocols and healthcare strategies. As the global community continues to navigate the challenges posed by COVID-19, understanding the intricacies of its impact on pediatric populations remains crucial. This research not only contributes valuable insights into the intersection of COVID-19, MIS-C, and renal health in children but also underscores the importance of continued vigilance and comprehensive care in the face of a pandemic that continues to reveal new dimensions of its effects on human health.

Discussion: Exploring the Nuances of AKI in Pediatric COVID-19 Patients

In the initial stages of the COVID-19 pandemic, children were widely regarded as less susceptible to severe outcomes compared to adults. The prevailing sentiment was that the younger population faced a lower risk of infection and, when infected, experienced a milder clinical course. However, emerging cohort studies and case reports soon began to challenge this assumption, shedding light on the occurrence of kidney involvement in pediatric COVID-19 cases. Among these, the condition known as Multisystem Inflammatory Syndrome in Children (MIS-C), associated with COVID-19, prompted particular concern due to reports suggesting a heightened risk of acute kidney injury (AKI).

Despite these early indicators, a comprehensive consensus on the incidence, outcomes, and mortality related to AKI in the context of MIS-C remained elusive. This gap in knowledge led to the initiation of our study, which aimed to delve into the prevalence of AKI among children with post-COVID MIS-C, assessing the severity and outcomes across various stages of the disease.

Our findings reveal a significant variance in the reported incidence of AKI among pediatric COVID-19 patients, with our study identifying AKI in 37% of MIS-C cases and 7.8% of all COVID-19 pediatric admissions. This rate starkly contrasts with other findings, such as those by Grewal et al., who reported a 24% incidence of AKI among total COVID-19 cases, and a systematic review which noted AKI in 20% of MIS-C patients. The discrepancies observed can likely be attributed to differences in the definitions of AKI used, hospitalization rates, the presence of comorbid conditions, and the overall incidence of MIS-C cases. Notably, studies utilizing the KDIGO criteria for AKI reported a higher incidence compared to those employing alternative definitions, highlighting the impact of methodological differences on reported outcomes.

The pathophysiology behind AKI in COVID-19 patients is multifaceted, encompassing dehydration, compromised cardiac output, cytokine storms, microvascular thrombosis, and the direct viral impact on renal cells. For children with MIS-C, renal hypoperfusion emerges as a primary concern, exacerbated by prolonged ICU stays, vulnerability to hypoxemia, and elevated markers of cardiac dysfunction.

Our cohort’s clinical presentation underscored fever and dyspnea as predominant symptoms, with a significant portion of stage 3 AKI patients requiring oxygen therapy or invasive mechanical ventilation. This aligns with other reports, suggesting hypoxemia’s critical role in the pathogenesis of AKI.

The development and exacerbation of AKI were associated with various comorbidities in both children and adults. Kidney biopsies in a subset of our patients revealed a spectrum of renal pathologies, echoing findings in adult populations and highlighting the complexity of renal involvement in COVID-19.

Our analysis of AKI severity and management strategies revealed no stark differences in outcomes based on age, comorbidities, or treatment interventions like inotropes and mechanical ventilation. The deployment of hemodialysis, particularly in stage 3 AKI cases, demonstrated the critical role of renal replacement therapies in managing severe cases, despite the constraints posed by the unavailability of continuous modalities in our setting.

The length of PICU stay and mortality rates in our cohort offered insights into the impact of AKI on the overall disease course, with a noted variability in outcomes based on the severity of the condition and the standards governing PICU admission and discharge practices.

Finally, the relatively low mortality rates observed in our study, compared to other regions, underscore the significance of early detection, avoidance of nephrotoxic agents, and prompt management of renal function abnormalities. The absence of residual renal impairment in a majority of our patients at discharge, coupled with normal follow-up findings, highlights the potential for recovery in pediatric patients, provided that comprehensive and timely care is administered.

This discussion not only reinforces the critical nature of AKI as a complication of MIS-C but also underscores the necessity for ongoing research and tailored management strategies to mitigate its impact on pediatric COVID-19 patients.

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