COVID-19 Causes AKI (acute Kidney Injury)-How Vulnerable Are The Kidneys?
Mar 14, 2022
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COWID-19 and the multisystem inflammatory syndrome in children: how vulnerable are the kidneys?
Vimal Chadha and Bradley A. Warady
When affected by coronavirus disease 2019 (COVID-19), most children have milder disease than what is experienced by adults. However, a subset of these children develops a multisystem inflammatory syndrome that can lead to shock and multiorgan failure. In the current issue, Basalely et al. characterize acute kidney injury (AKI) in pediatric patients with acute COVID-19 and multisystem inflammatory syndrome. Despite the associated morbidity, this cohort provides evidence of kidney recovery in most affected children.
vulnerable kidneys
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as the cause of coronavirus disease 2019 (COVID-19) in Hubei province, China, in December 2019 and was declared a pandemic in March 2020. Although the adult case fatality rate of 3.4% for SARS-CoV-2 is lower than those reported for SARS CoV-1 in 2003 (9.6%) and Middle East respiratory syndrome coronavirus (35%), the former is much more contagious and as a result, has become a pandemic of historic proportions. COVID-19 and its 2 predecessors share many important features in their clinical presentations and in their propensity for progression to severe disease involving multiple organs with high rates of morbidity. Although predominantly a respiratory infection, COVID-19 often progresses to a multisystem disorder, with kidney involvement common in adult patients who experience moderate to severe disease.
Early reports from China described high rates of hematuria and proteinuria, but relatively low rates of acute kidney injury (AKI), associated with COVID- 19. Highly variable rates of AKI (Acute kidney injury) in adults have since been reported from Europe and the United States, with a lack of uniformity in the cohort being described (e.g., hospitalized vs. intensive care) believed to be an important factor resulting in the variability of reported rates, and a factor further impacted by the evolution of hospitalization patterns that have occurred over the course of the pandemic. For example, although AKI (Acute kidney injury) occurred in 56.9% of 3345 hospitalized adults with COVID-19 in the Montefiore Health System (Bronx, NY), a much higher rate (87.2%) was seen in the subset of patients who required intensive care unit (ICU) admission.1 This rate of ICU-related AKI (Acute kidney injury) is greater than the rate of 57.3% reported by the Acute Kidney Injury–Epidemiologic Prospective Investigation study (international cross-sectional study performed in 97 ICUs) that found similar risk-adjusted rates of AKI (Acute kidney injury) and mortality worldwide.2 Studies comparing the risk of AKI (Acute kidney injury) in COVID-19 patients with retrospective cohorts of patients hospitalized with severe influenza have found that although the overall risk of AKI (Acute kidney injury) was similar in the 2 groups of patients, stage 3 AKI (Acute kidney injury), as defined by Kidney Disease: Improving Global Outcomes (KDIGO), was almost 3 times more common in patients with COVID-19.3 A substantial percentage (up to 28.5%) of adult COVID-19 patients with AKI (Acute kidney injury) have, in turn, been reported to require renal replacement therapy, a development that has been associated with mortality rates as high as 75% to 90%.1,2,4 In addition, up to one-third of those who have survived following renal replacement therapy did not achieve full recovery of kidney function at the time of discharge.4
COVID-19 causes kidney infection and AKI (acute kidney injury)
For reasons that are still speculative, children and adolescents make up a small proportion of COVID-19 cases. National statistics from countries in Asia, Europe, and North America have revealed that pediatric cases account for 2.1% to 7.8% of confirmed COVID-19 cases; however, the actual incidence is likely much higher as COVID-19 disease in most children and adolescents is associated with mild symptoms (if any symptoms at all) and may not prompt confirmatory testing. The mild symptoms of the disease in children, with particular reference to kidney function, were initially borne out in a retrospective observational study of 238 children admitted to Wuhan Children’s Hospital with COVID-19, in which the reported incidence of AKI (Acute kidney injury) was only 1.2%. Subsequent pediatric studies from Saudi Arabia and the United Kingdom did report much higher AKI (Acute kidney injury) rates of between 21% and 29% in children hospitalized with COVID-19, highlighting the importance of further investigation of this complication in children. In this issue of Kidney International, Basalely et al. do just that by providing additional data on the incidence, clinical characteristics, and outcomes of COVID-19 in a cohort of 152 children (aged <18 years) who were admitted to 4 New York hospitals during the height of the COVID-19 pandemic.5 AKI (Acute kidney injury) developed in 11.8% (18 patients) of this cohort (combined acute COVID-19 and multisystem inflammatory syndrome in children [MIS-C]) and completely resolved in 83% of them. These findings are in contrast to a cross-sectional point prevalence study of AKI (Acute kidney injury) in COVID-19 patients that reported the development of AKI (Acute kidney injury) in nearly half (44%) of 106 children admitted to ICUs in 41 centers, 32 of which were United States-based.6 It is noteworthy that the AKI (Acute kidney injury) rate in the cohort reported by Basalely et al. increases to 28% if only the 60 patients who required intensive care are considered. Of interest, this AKI (Acute kidney injury) rate is similar to the rate of 26.9% seen in a review of 4683 patients reported by the Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology (AWARE) study, a multinational, prospective study designed to describe AKI (Acute kidney injury) epidemiology in critically ill children.7 In addition, the percentage of ICU patients with severe AKI (Acute kidney injury) (KDIGO AKI stage 2–3) reported by Basalely et al. (13.3%) also approximates the incidence of severe AKI (Acute kidney injury) (11.6%) seen in the AWARE study. The length of hospitalization was significantly impacted by the presence of AKI, and one patient with AKI (Acute kidney injury) (representing 5% of all AKI patients and 12.5% of those with severe AKI (Acute kidney injury)) died, with the latter rate being similar to that reported by AWARE (11% mortality with severe AKI (Acute kidney injury)) but significantly less than the adult COVID-19 experience.
Unique to the pediatric population of COVID-19 patients has been the development of a constellation of clinical findings coined the MIS-C. In midMay 2020, the Centers for Disease Control and Prevention published a case definition for this syndrome, characterized by fever and inflammation (Table 1), a presentation similar to Kawasaki disease. It was detected in children and adolescents, aged <21 years, and was found to be temporally associated with SARS-CoV-2 infection. MIS-C is hypothesized to be primarily postinfectious in nature and distinct from COVID-19 as it occurs 2 to 4 weeks after infection with SARS-CoV-2. Although this COVID-19–associated disorder is uncommon (2 in 100,000 persons aged <21 years) when compared with COVID-19 cases (322 in 100,000), it can lead to serious and life-threatening complications. The disorder is distinct from Kawasaki disease as patients with MIS-C are older (average age, >7 years), have intense inflammation, and have a greater myocardial injury than patients with Kawasaki disease, and are more likely to be non-Hispanic Blacks. Because of the multisystem involvement that is characteristic of MIS-C, there have been concerns regarding the possible frequent development of AKI (Acute kidney injury) in this group of patients as a higher percentage (80%) of them receive intensive care, 20% receive mechanical ventilation, and 48% receive vasoactive support, all of which are associated with a higher risk of AKI (Acute kidney injury).8
Children and adolescents kidney function are more vulnerable to COVID-19
Fortunately, in a report of 186 patients with MIS-C from 26 states in the United States, AKI (Acute kidney injury) was diagnosed in <10%, while the most commonly involved organ systems were gastrointestinal (92%), cardiovascular (80%), hematologic (76%), mucocutaneous (74%), and respiratory (70%).9 In addition, in a recent report comparing the course of 577 children and adolescents with acute COVID-19 and 539 with MIS-C, the presence or absence of AKI (Acute kidney injury) was not even commented on. However, there has been a spectrum of AKI (Acute kidney injury) rates reported from pediatric centers globally, with most cases being mild and transient in nature (Table 2). In the publication by Basalely et al., 55 of the 152 hospitalized patients (36.2%) were, in fact, diagnosed with MIS-C. The greater severity of illness associated with MIS-C compared with acute COVID-19 disease in the remaining 97 patients was reflected by the greater percentage of children with MIS-C who developed AKI (Acute kidney injury) (18.2% vs. 8.2%), who had stage 3 AKI (Acute kidney injury) (40% vs. 25%), and who required intensive care (61.8% vs. 27%). Most of the patients (80% with MIS-C and 50% with COVID-19) who developed AKI (Acute kidney injury) were found to have decreased kidney function at the time of hospital admission, often with gastrointestinal symptoms, suggesting a possible prerenal etiology. Echocardiographic evidence of systolic dysfunction was more common in patients with MIS-C who had AKI (Acute kidney injury) compared with those who did not, a finding that has also been seen by others and that suggests the possible contribution of renal hypoperfusion to the impaired kidney function. Nevertheless, none of the patients with MIS-C required renal replacement therapy, and 9 of 10 patients had resolution of AKI (Acute kidney injury) before hospital discharge. With 6 of the 8 acute COVID-19 patients also demonstrating resolution of AKI (Acute kidney injury), these data further suggest that the kidney injury in pediatric patients with COVID-19 and MIS-C is not severe in most instances.
At present, children aged <16 years are not eligible for a vaccination against SARS-CoV-2 and thus we are likely to continue to see children with COVID-19 and MIS-C in the foreseeable future. Although the information presented by Basalely et al. is informative and optimistic in terms of the generally favorable AKI (Acute kidney injury)-related outcome, the limited experience presented precludes any definitive statement regarding the epidemiology of COVID-19–related AKI (Acute kidney injury) in children and highlights the importance of ongoing multicenter/national surveillance of the affected pediatric population with sharing of those experiences as a means to ideally optimize care until universal prevention can be achieved.
Acute renal failure: AKI (Acute kidney injury)
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