Role of selenium in the pathophysiology of cardiorenal anaemia syndrome

Abstract

Chronic kidney disease (CKD) and cardiovascular disease (CVD) have multiple bidirectional mechanisms, and anaemia is one of the critical factors that are associated with the progression of the two disorders [referred to as cardiorenal anaemia syndrome (CRAS)]. Several lines of evidence indicate that CRAS confers a worse prognosis, suggesting the need to clarify the underlying pathophysiology. Among the micronutrients (trace elements) that are essential to humans, inadequate iron status has previously been implicated in the pathogenesis of CRAS; however, the roles of other trace elements remain unclear. Selenium critically regulates the function of selenoproteins, in which selenocysteine is present at the active centres. The human genome encodes 25 selenoproteins, and accumulating data indicate that they regulate diverse physiological processes, including cellular redox homeostasis, calcium flux, thyroid hormone activity and haematopoiesis, all of which directly or indirectly influence cardiac function. The essential role of selenium in human health is underscored by the fact that its deficiency results in multiple disorders, among which are cardiomyopathy and abnormal erythrocyte morphology. Studies have shown that selenium deficiency is not uncommon in CKD patients with poor nutritional status, suggesting that it may be an under-recognized cause of anaemia and cardiovascular disorders in these patients. In this review, we discuss the role of selenium in the pathophysiology of CKD, particularly in the context of the interconnection among CKD, cardiac dysfunction and anaemia. Given that selenium deficiency is associated with treatment-resistant anaemia and an increased risk of CVD, its role as a key modulator of CRAS merits future investigation.

Keywords: cardiomyopathy; chronic kidney disease; micronutrients; selenium deficiency; trace element.

Figure 1

Overview of selenium (Se) metabolism and selenoprotein synthesis. In nature, Se exists in inorganic [selenate (SeO₄ ²⁻) and selenite (SeO₃ ²⁻)] and organic [selenomethionine and selenocysteine (Sec)] forms. Selenomethionine is the principal nutritional source of Se in the human diet, which is converted to Sec through the transsulfuration pathway. Sec is catalysed to selenide by Sec lyase, which is used to synthesize selenoproteins. Selenate and selenite, taken as supplements or fortified foods, are also reduced to selenide and are used for selenoprotein synthesis.

Figure 2

Role of selenium (Se) in the pathophysiology of cardiorenal anaemia syndrome. In chronic kidney disease (CKD) patients, suboptimal Se status and reduced selenoprotein activity trigger the occurrence of cardiovascular diseases (CVDs) through multiple mechanisms, including impaired redox homeostasis and altered Ca²⁺ signalling in the endoplasmic reticulum. In addition, Se deficiency aggravates anaemia through increased erythrocyte fragility and reduced stress erythropoiesis, which also contributes to the increased risk of CVD in CKD.