Early data from the coronavirus disease 2019-2020 (SARS-Cov-2) pandemic indicated that up to 20% of severely infected patients develop acute kidney injury (AKI) [1, 2]. The prognosis of patients who progress to severe AKI is dismal, with a near 100% mortality-rate among those requiring acute dialysis. In addition, nearly 50% of patients exhibit proteinuria or hematuria, which is an uncommon feature in hospitalized AKI, suggesting a more complex and lasting injury than previously appreciated. These complications have not been well characterized . Given that the prevalence of CKD among Veterans is higher than the general population, the potential threat of this pandemic to the kidney health of US Veterans is substantial and accurate information on the overall incidence, nature, and prognosis of AKI is needed as well as to better understand whether risk for developing AKI or its severity are modifiable.
1.Arentz M, Yim E, Klaff L, et al. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA 2020; 323: 1612-1614.
2.Lee JR, Silberzweig J, Akchurin O, et al. Characteristics of Acute Kidney Injury in Hospitalized COVID-19 Patients in an Urban Academic Medical Center. Clin J Am Soc Nephrol 2020.
The goals of this proposal are to: 1) Compare the incidence and nature of AKI in US Veterans hospitalized with COVID-19 versus Influenza infection, 2) Compare the short-term natural history and prognosis of patients with COVID-19 associated AKI (COV19-AKI) and 3) Identify modifiable and nonmodifiable risk factors for the development of COV19-AKI and its prognosis.
We conducted a national retrospective cohort study of Veterans aged 18 and older who were admitted with COVID-19 or influenza between 10/01/2019 and 05/31/2020. Data were obtained from the electronic health record utilized by the Veterans Affairs (VA) Health Administration, which is comprised of the Veterans Health Information and Technology Architecture (VistA) and Computerized Patient Record System (CPRS). 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 due to the infeasibility of obtaining informed consent for a large national cohort.
Data from 10/01/2018 to 09/24/2020 were collected from the Observational Medical Outcomes Partnership (OMOP) version 5 common data model transformation of the National Corporate Data Warehouse as well as the COVID-19 Shared Resource. Complete hospitalization information was available for all patients. Baseline comorbidity data and inpatient conditions, vital signs, laboratory data, and exposures were obtained from available records. 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 (ICD) versions 9 (ICD-9) and 10 (ICD-10) and Current Procedural Terminology (CPT) codes (Supplemental Materials Definitions). Laboratory tests were identified by Logical Observation Identifiers Names and Codes (LOINC®). Medications were obtained from outpatient VA pharmacy fill records and inpatient bar-coded medication administration (BCMA) and categorized using the Anatomical Therapeutic Chemical (ATC) classification and RxNorm.
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 excluded patients who underwent nephrectomy during the hospitalization and patients with a baseline eGFR <15 ml/min/1.37m2, kidney transplantation, or end-stage renal disease (ESRD) before index hospitalization. In patients who had more than one 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.
The primary exposures in this study were infection with COVID-19 or influenza. Two groups were defined: 1) Patients with a positive COVID-19 test within 14 days prior to or during the hospitalization; and 2) Patients with a positive influenza A or influenza B test within 14 days prior to or during the hospitalization. Patients were diagnosed with COVID-19 or influenza by PCR-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 creatinine-based criteria: stage I, 0.3 mg/dl creatinine increase from baseline or creatinine 1.5 to 1.9 times baseline; stage II, creatinine 2.0 to 2.9 times baseline; and stage III, creatinine 3.0 times baseline or initiation of dialysis.23 Recovery from AKI was defined by serum creatinine value within 20% of baseline serum creatinine, obtained within the following timeframes: within 4 days, 30 days, and 90 days of peak serum creatinine. Baseline serum creatinine to define AKI was the mean outpatient serum creatinine value 7-365 days before hospitalization.24 Among those without a known preadmission baseline, we used the lowest serum creatinine during hospitalization.
The primary analysis compared rates of AKI incidence during hospitalization, mortality during hospitalization and within 90 days of peak serum creatinine, and AKI recovery occurring within 90 days of peak serum creatinine between patients hospitalized with COVID-19 or influenza. To account for measured confounding, an inverse probability of treatment weighted (IPTW) cohort was created that balanced the distributions of over 50 observed covariates. The weights were calculated using the matching weight formula that creates covariate distributions similar to a one-to-one propensity score matched cohort. The propensity score used for the weighting was calculated via a logistic regression model predicting COVID-19 versus influenza. The model included 55 pre-hospitalization covariates including major variables known to increase the risk for mortality. Covariate balance in the IPTW cohort was assessed using standardized mean differences.
A total of 3402 hospitalizations for COVID-19 and 3680 hospitalizations for influenza admitted between October 1, 2019 and May 31, 2020 were studied using the electronic medical record. We found that AKI 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 AKI but was similar among survivors.
We observed a substantial incidence of AKI in influenza, with one-quarter of patients experiencing AKI during hospitalization. The potential added burden of AKI related to influenza in addition to AKI during hospitalization with COVID-19 could have downstream implications for resource utilization. Other studies have described their experience in the COVID-19 epicenter in the early months of the pandemic, including increased demand for kidney replacement therapy and decreased capacity to provide it, with COVID-19 affecting both their workforce (e.g., dialysis nurses) and dialysis supplies. Given the strain on the health system due to COVID-19, the overall increased burden of kidney disease and its resource allocation due to these illnesses will be important to project. The proportion of patients with AKI who remain dialysis-dependent at discharge in our study suggests that the impact may extend to outpatient dialysis centers.
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Kidney Disorders, Infectious Diseases
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