Description

The coronavirus disease caused by the SARS-CoV-2 first emerged in early December 2019 and was declared a pandemic on March 2020. SARS-CoV-2 infection is produced by binding to ACE2, which among other sites is highly expressed in the endothelial cells of the blood vessels, pericytes and the heart, as well as in renal podocytes and proximal tubular epithelial cells. Of note, ACE2 RNA expression in kidney is nearly 100-fold higher than that in lungs. COVID-19 and cardiovascular disease (CVD) seem to be interconnected; on the one hand, prior CVD as well as CV risk factors are associated with an increased incidence of the disease (with fatal outcomes) and on the other hand COVID-19 can exacerbate associated CVD and determine de novo cardiac complications (acute myocardial injury, stress cardiomyopathy, myocarditis, pericarditis, arrhythmias, heart failure and cardiogenic shock). At the same time, COVID-19 disease can lead to acute kidney injury directly, or due to sepsis, multi-organ failure and shock. The preexistence of both CVD and CKD is associated with a higher risk of severe disease and worse prognosis. CKD patients are already at high risk for CV complications with CVD the leading cause of morbidity and mortality in CKD.

The reported incidence of thrombotic complications in patients with COVID-19 varies between studies, ranging from 25% to 42.6%. It is still under debate if these hemostatic changes are a particular effect of SARS-CoV-2, the inflammatory response, or if they appear secondary to either endothelial dysfunction (ED) or sepsis. Prolonged hypoxemia, cytokine storm and local pulmonary thrombotic phenomena, as well as the associated liver dysfunction secondary to the viral binding to a hepatic receptor are some of the COVID-19's peculiarities that can lead to a higher thrombotic burden. Infection of endothelial cells or perycites is of particular importance because this could lead to severe microvascular and macrovascular dysfunction. ED refers to a systemic condition in which the endothelium loses its physiological properties, including the tendency to promote vasodilation, fibrinolysis, and anti-aggregation. Morphologic findings from deceased patients confirm the presence of viral elements within endothelial cells and an accumulation of inflammatory cells, with evidence of endothelial and inflammatory cell death. Endothelitis in several organs as a direct consequence of viral involvement and of the host inflammatory response may explain the impaired microcirculatory function in different vascular beds and clinical sequel in patients with COVID-19.

The COVID-19 pandemic is forcing healthcare systems and societies to scrutinize how care is delivered and valuable lessons are being learned. Furthermore, as mentioned above, the assessment of CV risk is crucially important for these patients. In this regard, a bedside assembly of reliable and thorough investigations that will provide lasting insights past the time of this pandemic, can become a very valuable tool.

The overall scope of this study is to assess the CV risk in a CKD (stage 3 to 5D) and kidney transplanted population, following COVID-19 infection, with focus on the ED as compared to a control group of matched patients. By using clinical evaluation, flow-mediated dilatation (FMD), pulse wave velocity (PWV), intima media thickness (IMT), echocardiographic parameters, Lung ultrasonography (LUS), bioimpedance spectroscopy (BIS) derived fluid status parameters (over hydration, total body water, extracellular water and intracellular water) and a series of novel biomarkers, the investigators intent to determine the long-term impact of this disease on CV and renal outcomes in the aforementioned population.