Kidney Outcomes in Long COVID

Bowe, Benjamin; Xie, Yan; Xu, Evan; Al-Aly, Ziyad

Background: COVID-19 is associated with increased risk of post-acute sequelae involving pulmonary and extrapulmonary organ systems - referred to as long COVID. However, a detailed assessment of kidney outcomes in long COVID is not yet available. Methods: We built a cohort of 1,726,683 US Veterans identified from March 01, 2020 to March 15, 2021 including 89,216 30-day COVID-19 survivors and 1,637,467 non-infected controls. We examined risks of AKI, eGFR decline, ESKD, and major adverse kidney events (MAKE) defined as eGFR decline ≥50%, ESKD, or all-cause mortality using inverse probability weighted survival regressions, adjusting for predefined demographic and health characteristics, and algorithmically selected high-dimensional covariates including diagnoses, medications, and laboratory tests. Linear mixed models characterized intra-individual eGFR trajectory. Results: Beyond the acute illness, 30-day survivors of COVID-19 exhibited a higher risk of AKI (aHR=1.94 (95%CI: 1.86,2.04)), eGFR decline ≥30% (1.25 (1.14,1.37)), eGFR decline ≥40% (1.44 (1.37,1.51)), eGFR decline ≥50% (1.62 (1.51,1.74)), ESKD (2.96 (2.49-3.51)), and MAKE (1.66 (1.58,1.74)). There was a graded increase in risks of post-acute kidney outcomes according to the severity of the acute infection (whether patients were non-hospitalized, hospitalized, or admitted to intensive care). Compared to non-infected controls, 30-day COVID-19 survivors exhibited excess eGFR decline of -3.26 (-3.58, -2.94), -5.20 (-6.24, -4.16), and -7.69 (-8.27, -7.12) mL/min/1.73m2/year in non-hospitalized, hospitalized, and those admitted to intensive care during the acute phase of COVID-19 infection. Conclusions: COVID-19 survivors exhibited increased risk of kidney outcomes in the post-acute phase of the disease. Post-acute COVID-19 care should involve attention to kidney disease.