Part 1:Comparison Of COVID-19 Versus Influenza On The Incidence, Features, And Recovery From Acute Kidney Injury in Hospitalized United States Veterans

Contact: emily.li@wecistanche.com

Bethany C.Birkelol, et al

Kidney Injury

Acute kidney injury is a common complication in patients hospitalized with SARS-CoV-2 (COVID-19), with prior studies implicating multiple potential mechanisms of injury. Although COVID-19 is often compared to other respiratory viral illnesses, few formal comparisons of these viruses on kidney health exist. In this retrospective cohort study, we compared the incidence, features, and outcomes of acute kidney injury among Veterans hospitalized with COVID-19 or influenza and adjusted for baseline conditions using weighted comparisons. A total of 3402 hospitalizations for COVID-19 and 3680 hospitalizations for influenza admitted between October 1, 2019, and May 31, 2020, across 127 Veterans Administration hospitals nationally were studied using the electronic medical record. Acute kidney injury occurred more frequently among those with COVID-19 compared to those with influenza(40.9% versus 29.4%, weighted analysis) and was more severe. Patients with COVID-19 were more likely to require mechanical ventilation and vasopressors and experienced higher mortality. Proteinuria and hematuria were frequent in both groups but more common in COVID-19. Recovery of kidney function was less common in patients with COVID-19 and acute kidney injury but was similar among survivors. Thus, findings from this study confirm that acute kidney injury is more common and severe among patients hospitalized with COVID-19 compared to influenza, a finding that may be driven largely by illness severity. Hence, the combined impact of these two illnesses on kidney health may be significant and have important implications for resource allocation.

KEYWORDS: acute kidney injury; COMD-19; hematuria; influenza; proteinuria Published by Elsevier, Inc., on behalf of the International Society of Nephrology.

Acute kidney injury (AKI) is a well-recognized complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(coronavirus disease 2019 [COVID-19]), LLC

occurring in one-third of hospitalized patients and up to three-quarters of critically ill patients, with associated in-hospital mortality rates of up to 50%."The reasons underlying the high AKI incidence rates and associated poor outcomes are not well understood. High rates of hematuria and proteinuria have also been observed in COVID-19.

The extent to which these findings differ from other severe viral respiratory illnesses is unknown. Although informal comparisons to influenza have been made, few direct comparisons have been performed. Literature on AKI in influenza suggests some risk factors common to both illnesses, such as those related to illness severity(e.g., critical illness and mechanical ventilation). Similarly, elevated inflammatory markers have been observed in both influenza and COVID-19 and are often associated with AKI,,2 whereas histopathologic data and clinical studies suggest ischemic injury as the predominant etiology of AKI in both illnesses.-19Further understanding of the relative and combined burden of AKI in these 2 illnesses is critical. We hypothesized that patients with COVID-19 would have higher rates and severity of AKI than similar patients hospitalized with influenza. To test this hypothesis, we compared the incidence, risk factors, clinical features, and recovery from AKI in a retrospective study of veteran patients hospitalized with either COVID-19 or influenza.

METHODS

Study setting and design

We conducted a national retrospective cohort study of veterans, aged ≥18 years, who were admitted with COVID-19 or influenza between October 1, 2019, and May 31, 2020. Data were obtained from the electronic health record utilized by the Veterans Affairs (VA) Health Administration, which is composed of the Veterans Health Information and Technology Architecture and Computerized Patient Record System. This study was approved by the Institutional Review Board and the Research and Development Committee of the Tennessee Valley Healthcare System VA. The requirement for informed consent was waived because of the infeasibility of obtaining informed consent for a large national cohort.

Data collection

Data from October 1, 2018, to September 24, 2020, were collected from the Observational Medical Outcomes Partnership version 5 common data model transformation of the National Corporate Data Warehouse, which aggregates data from all VA facilities, and the VA COVID-19 Shared Data Resource.20-2 Complete hospitalization information was available for all patients. Baseline co-morbidity data were obtained from available records up to the day of hospital admission. Inpatient conditions, vital signs, laboratory data, and exposures were obtained from records from admission through discharge. Kidney function and mortality outcomes were collected from VA laboratory data, administrative diagnosis and procedure codes, and VA vital status files. Diagnoses and procedures were defined using the International Classification of Diseases, Ninth Revision (ICD-9), International Classification of Diseases, Tenth Revision (ICD-10), and Current Procedural Terminology codes(Supplementary Table S1). Laboratory tests were identified by Logical Observation Identifiers Names and Codes. Medications were obtained from outpatient VA pharmacy fill records and inpatient barcoded medication administration and categorized using the Anatomical Therapeutic Chemical classification and RxNorm.

Cohort exclusion criteria

Within the predefined study time frame and across 127 VA hospitals nationally, we identified 8454 hospitalizations that included a diagnosis of COVID-19 or influenza. Eligibility criteria included either a premorbid outpatient serum creatinine value and at least 1 inpatient serum creatinine value or at least 2 serum creatinine values in the absence of a premorbid baseline value. We applied several exclusion criteria to provide the 2 clinically relevant cohorts, as illustrated in Figure 1. We excluded patients who underwent nephrectomy during the hospitalization and patients with a baseline estimated glomerular filtration rate （eGFR）<15 ml/min per 1.37 m²， kidney transplantation, or end-stage renal disease before index hospitalization. In patients who had >1 qualifying hospitalization during the study period, we restricted to the first qualifying hospitalization. Patients with both a positive COVID-19 and influenza test during the study period were excluded.

Definitions

The primary exposures in this study were infected with COVID-19 or influenza. Two groups were defined:(i)patients with a positive COVID-19 test within 14 days before or during the hospitalization; and (ii) patients with positive influenza A or influenza B test within 14 days before or during the hospitalization. Patients were diagnosed with COVID-19 or influenza by polymerase chain reaction-based or rapid antigen tests of nasopharyngeal, oropharyngeal, or respiratory specimens. The primary outcome in this study was AKI. AKI was defined using the peak in-hospital serum creatinine and staged using modified Kidney Disease: Improving Global Outcomes(KDIGO)creatinine-based criteria: stage 1,≥0.3 mg/dl creatinine increase from baseline or creatinine 1.5 to 1.9 times baseline; stage 2, creatinine 2.0 to 2.9 times baseline; and stage 3, creatinine 3.0 times baseline or initiation of dialysis. To more accurately compare AKI staging and recovery, we preferred to anchor our definition to a known baseline creatinine, which was available in 84% of patients with COVID-19 and 92% with influenza. Secondary outcomes included hematuria, proteinuria, kidney replacement therapy,

Figure 1 Cohort selection flow diagram. Exclusion criteria were applied to eligible hospitalizations to derive final study groups. COVID-19, coronavirus disease 2019; ESRD, end-stage renal disease.