Kidney involvement in acute COVID-19 and long-term cardiovascular outcomes: The role of inflammation and endothelial dysfunction

Abstract

COVID-19 is associated with long-term cardiovascular (CV) complications, potentially driven by persistent inflammation, coagulopathy, and endothelial dysfunction. The contribution of kidney dysfunction to this risk remains insufficiently characterized. The aim of this study was to evaluate the association between kidney involvement during acute COVID-19 and the development of CV events within one year after hospital discharge.

Methods. This prospective cohort study included 328 patients hospitalized with moderate to severe COVID-19, without known kidney or cardiovascular disease, followed for 12 months after discharge. Kidney involvement was defined as newly detected proteinuria >150 mg/L, an increase in serum creatinine ≥26 µmol/L, or a decline in estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m² during hospitalization. Additional assessments included C-reactive protein (CRP), D-dimer, and intercellular adhesion molecule-1 (ICAM-1). The primary endpoint was a composite of new-onset heart failure, therapy-requiring hypertension, arrhythmias, ischemic stroke or transient ischemic attack (TIA), and myocardial infarction within one year.

Results. CV complications occurred in 105 of 328 patients (32.0%) during follow-up. The most frequent were major adverse cardiovascular events (40.8%), arrhythmias (20.0%), and new-onset hypertension (16.8%); heart failure developed in 13.6%, myocardial infarction in 5.6%, and stroke/TIA in 3.2%. Patients with complications had higher serum creatinine (92.0 ± 50.8 vs. 81.8 ± 40.1 µmol/L; p=0.042), lower eGFR (83.2 ± 27.2 vs. 87.3 ± 25.5 mL/min/1.73 m²; p=0.092), and more frequent proteinuria. In multivariable logistic regression, each 10 mL/min/1.73 m² decrease in eGFR was associated with an 8% increase in CV risk (OR 1.08; 95% CI 1.01–1.16; p=0.044), while each 10 µmol/L rise in creatinine increased risk by 6% (OR 1.06; 95% CI 1.01–1.12; p=0.037). Patients with adverse outcomes had significantly higher D-dimer (2.90 ± 0.11 vs. 1.89 ± 0.07 mg/L; p<0.001), whereas CRP showed only a trend (38.3 ± 2.0 vs. 35.1 ± 1.1 mg/L; p=0.066). ICAM-1 concentrations remained threefold higher one year later in patients with CV events (522.7 ± 113.1 pg/mL) compared with controls (193.6 ± 93.7 pg/mL).

Conclusions. Kidney dysfunction during acute COVID-19 is an independent predictor of long-term CV complications. Persistent inflammation, hypercoagulability, and endothelial activation may represent the underlying mechanisms. These findings emphasize the need for integrated cardiorenal monitoring in COVID-19 survivors.