COVID-19 and AKI: Where Do We Stand?

In the year since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, .110 million individuals have been infected and .2.4 million deaths have been attributed to coronavirus disease 2019 (COVID-19) across the world. In the United States, we have seen similarly staggering numbers, with .27 million individuals infected and over 490,000 deaths as of the third week of February 2021. Although predominantly a respiratory infection, COVID-19 often results in multisystem disease, with kidney involvement common in patients with moderate to severe disease. Just as the virus has inundated our health care system, there has been a deluge of publications about SARS-CoV-2 and COVID-19; a search in PubMed returned .100,000 citations, with .800 related to COVID-19 and AKI. Despite this number of publications, it is important to ask what we truly know about kidney involvement in COVID-19 and what still needs to be learned. Early reports from China described high rates of hematuria and proteinuria but relatively low rates of AKI associated with COVID-19.1–3 Highly variable rates of AKI were subsequently reported from Europe and the United States, with some case series describing rates approaching 60% among hospitalized patients.4,5 In a recent meta-analysis, the prevalence of AKI among patients hospitalized with COVID-19 was 28%, rising to 46% among critically ill patients, with nearly 20% requiring support with RRT.6 Why has there been this high degree of variability in the reported rates of kidney involvement? One obvious factor relates to the denominator. Because rates have only been reported for hospitalized patients, differences in hospitalization patterns, ranging from hospitalization of all patients identified with infection in some early reports to only the most severely symptomatic patients during the surges in cases triggering latter reports, have likely skewed the data. Even in some of the initial reports from China, rates of AKI in critically ill patients were comparable with those seen in later reports.1 Data across the broader population of infected patients will be required to understand the true effect of COVID19 on the kidney. More robust longitudinal data will also be important to understand the effect, if any, of changes in viral strain or improvements in treatment on the frequency and severity of kidney involvement. Early reports from the Department of Veterans Affairs and from New York City have suggested a temporal decline in the incidence of COVID-19–associated AKI.7,8 Whether this is related to disease-specific factors, improvements in treatment, or changes to the overall stress on health care systems as the pandemic has surged and eased is unknown. The etiology of AKI associated with COVID-19 has also been controversial, with considerable debate over whether direct viral involvement of the kidney plays a significant role.9–12 Regardless of whether viral involvement of the kidney contributes, in the vast majority of patients AKI is attributable to volume depletion associated with hyperpyrexia and gastrointestinal involvement or associated with the severe systemic manifestations that cause multiorgan system failure in the most critically ill patients. Although the sheer number of patients with severe AKI has, at times, overwhelmed health care systems during surges in infection,13 rates of AKI are strikingly similar to those associated with other forms of sepsis. AKI has been reported in epidemiologic studies from Europe and China in approximately half of critically ill patients with sepsis.14,15 In a randomized, controlled trial of resuscitation strategies in severe sepsis and septic shock, AKI was present in approximately half of patients on presentation to the emergency department, and an additional 18.7% subsequently developed AKI during the first week of hospitalization, with two-thirds of patients having stage 2 or 3 AKI.16 Even among patients with communityacquired pneumonia, approximately one-third develop AKI in the absence of severe sepsis or shock.17 Thus, although the number of patients with COVID-19–associated AKI has far outstripped the numbers of sepsisassociated AKI seen outside of the pandemic, the rates of AKI are not disproportionate to those seen in other forms of sepsis.