The Association of Long COVID and CKD: Findings from the National Clinical Cohort Collaborative (N3C)

Background: Among patients with acute coronavirus disease-19 (COVID-19), the association of chronic kidney disease (CKD) and Long COVID has not been reported in large multi-center cohorts. Methods: This study used data from 59 healthcare systems across the United States, in the National Clinical Cohort Collaborative (N3C) COVID Enclave, to analyze the relationship between CKD and Long COVID among adults diagnosed with acute COVID-19 between October 2021 and September 2023. We conducted two main analyses. First analysis : we tested if baseline CKD (estimated glomerular filtration rates (eGFR) <60 ml/min/1.73m 2 or diagnostic code) or baseline end-stage kidney disease (ESKD) are risk factors for Long COVID (identified using ICD-10-CM code U09.9). We secondarily assessed associations between baseline mild CKD (Stage 3a, eGFR 45 -59 ml/min/1.73m 2 ) and Long COVID. Second Analysis : among patients without baseline CKD/ESKD, we examined if incident CKD/ESKD and eGFR decline (≥20% in one year) were associated with Long COVID. We used propensity score matching (PSM) for demographics and data-contributing site, with models adjusted for risk factors and competing risk of death. All outcomes were evaluated within a 365-day follow-up period from the onset of acute COVID-19. Results: First analysis : From an unmatched cohort of 2,385,20 patients with acute COVID-19, those with baseline CKD/ESKD had a higher risk of Long COVID (adjusted sub-distribution hazard ratio sHR 1.13, 95% confidence interval CI 1.09-1.18) after matching. A similar risk was noted even among those with mild CKD (sHR: 1.15, 95% CI 1.05-1.25). Second Analysis: Among patients with acute COVID-19 and without baseline CKD/ESKD, Long COVID was associated with incident CKD/ESKD (sHR 1.65, 95% CI 1.51-1.81) and 20% or greater eGFR decline (sHR 1.21, 95% CI 1.04-1.40) within one year. Conclusions: CKD, even mild, was associated with an higher risk of Long COVID. Among those without baseline CKD, Long COVID was associated with incident CKD and eGFR decline.