Increased Estimated GFR Is Negatively Associated With the Risk of SARS-CoV-2 Infection and Severe COVID-19 Within Normal to Mildly Decreased Levels: Nested Case-Control Study

Background: While accumulating evidence indicates chronic kidney disease as a risk factor for coronavirus disease 2019 (COVID-19), the association between normal or mildly decreased kidney function and COVID-19 is unaddressed. Here, we have examined the association of an increase in estimated glomerular filtration rate (eGFR) with the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes among patients within normal to mildly decreased kidney function.

Methods: The patients who participated in both health screenings from period I (2017-2018) to II (2019-2020) were enrolled to our study. All participants were categorized into four groups according to the changes in eGFR stage from period I to II: 1) persistently stage G1, 2) from stage G2 to G1, 3) from stage G1 to G2, 4) persistently stage G2. In addition, the changes in eGFR value were defined by subtracting its value of period I from II. Patients were followed up for SARS-CoV-2 infection from January 1, 2021 to any diagnosis of COVID-19 or December 31, 2021, whichever happened first. In addition, those with SARS-CoV-2 infection were followed-up for one month after diagnosis to analyze severe COVID-19. Adjusted odds ratio (aOR) was calculated using multivariable-adjusted logistic regression.

Results: We identified 159,427 patients with and 1,804,798 patients without SARS-CoV-2 infection. The risk of SARS-CoV-2 infection decreased when eGFR stage changed from G2 to G1 (aOR, 0.957; 95% confidence interval [CI], 0.938-0.977) and persistently maintained at G1 (aOR, 0.966; 95% CI, 0.943-0.990), compared with the persistently stage G2 group. In addition, the risk showed an inverse relationship with changes in eGFR value, which was depicted by restricted cubic spline curves. For the overall risk of severe COVID-19, the persistently stage G1 showed the lowest risk (aOR, 0.897; 95% CI, 0.827-0.972), followed by those from stage G1 to G2 (aOR, 0.900; 95% CI, 0.828-0.978) and those from stage G2 to G1 (aOR, 0.931; 95% CI, 0.871-0.995), compared with the persistently stage G2 group.

Conclusion: An increase in eGFR was negatively associated with the risk of SARS-CoV-2 infection and severe COVID-19 among normal or mildly decreased kidney function. For severe COVID-19, maintaining higher baseline eGFR may act as a protective factor against its risk.