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Does COVID-19 Increase the Risk of Subsequent Kidney Diseases More Than Influenza? A Retrospective Cohort Study Using Real-World Data In the United States

Background: Although case reports and observational studies suggest Coronavirus disease 2019 (COVID-19) increases the risk of kidney diseases, definitive real-world evidence, especially in comparison with influenza, is lacking. Our study aims to assess the association between COVID-19 infections and subsequent kidney diseases, using influenza as a positive control and incorporating a negative control to establish clearer associations. Methods: A large retrospective cohort study with strata matching was conducted using the MarketScan database with records from Jan. 2020 to Dec. 2021. We used the international classification of 10th revision (ICD-10) codes to identify individuals and build three cohorts, (1) COVID-19 group, with index dates as the diagnosis dates of COVID-19; (2) Influenza but no COVID-19 (positive control) group, with index dates as the diagnosis dates of Influenza; and (3) no COVID-19 / Influenza (negative control) group, with randomly assigned index dates between Jan. 2020 to Dec. 2021. The main outcomes were acute kidney injury (AKI), chronic kidney disease (CKD), and end-stage renal disease (ESRD). To evaluate the association between COVID-19 and the new onset of kidney diseases relative to both control groups, we employed multivariable stratified Cox proportional hazards regression analysis. Results: The study included 939,241 individuals with COVID-19, 1,878,482 individuals in the negative control group, and 199,071 individuals with influenza. After adjusting for demographics, comorbidities, and medication histories, COVID-19 was significantly associated with increased risks of AKI (adjusted hazards ratio, aHR: 2.74, 2.61-2.87), CKD (aHR: 1.38, 1.32-1.45), and ESRD (aHR, 3.22; 95% CI, 2.67-3.88), while influenza was associated with a modestly increased risk of AKI (aHR: 1.24, 1.11-1.38) and had no impact on CKD (aHR: 1.03, 0.92-1.14), and ESRD (aHR, 0.84; 95% CI, 0.55-1.29). Time-specific analyses indicated that while the HR for AKI declined from 0-180 days to 0-540 days, the HR for CKD and ESRD remained stable, with COVID-19’s risk surpassing influenza’s risk throughout follow-up. Exploratory analysis also found significant impacts of COVID-19 on glomerular diseases (aHR 1.28, 95% CI 1.09-1.50). Conclusion: In this large real-world study, COVID-19 infections were associated with a 2.3-fold risk of developing AKI, a 1.4-fold risk of CKD, and a 4.7-fold risk of ESRD compared to influenza. Greater attention needs to be paid to kidney diseases in individuals after contracting COVID-19 to prevent future adverse health outcomes.