Cardiorenal Syndrome in End-Stage Kidney Disease

Cardiorenal syndrome (CRS) in patients with end-stage kidney disease (ESKD) represents mainly cardiovascular disease (CVD) due to various complications associated with renal dysfunction-defined as type 4 CRS by Ronco et al.-because the effect of cardiac dysfunction on the kidneys does not need to be taken into consideration, unlike in non-dialysis dependent chronic kidney disease (CKD).

Patients with ESKD are often in a state of chronic inflammation due to the upregulation of proinflammatory cytokines. Chronic inflammation leads to malnutrition and consequently to vascular endothelial dysfunction and vascular calcification, which is referred to as malnutrition-inflammation-atherosclerosis (MIA) syndrome and acts as a major risk factor for CVD. Anemia also plays a crucial role in CVD, and individuals with erythropoietin-resistant anemia have a particularly high risk of CVD. However, caution is emphasized because not only anemia itself, but also the overtreatment of anemia with erythropoiesis-stimulating agents aimed at elevating hemoglobin to ≥13 g/dl can also increase the risk of CVD. In CKD-mineral and bone disorder (CKD-MBD), phosphate load triggers the interactions between various factors such as calcium, parathyroid hormone, vitamin D, and fibroblast growth factor 23, promoting vascular calcification and thus becoming a risk factor for CVD.

In addition to traditional atherosclerosis risk factors such as hypertension, diabetes, and dyslipidemia, the involvement of MIA syndrome, anemia, and CKD-MBD accompanying CKD have also become a focus for investigation as major players in CRS in patients with ESKD.