Role of oxidative stress and indoxyl sulfate in progression of cardiovascular disease in chronic kidney disease

Abstract

Several abnormalities of the cardiovascular system are observed in most cases of chronic kidney disease (CKD). Mechanisms underlying these abnormalities are complicated, and several factors contribute to their pathogenesis. Of these factors, oxidative stress and uremic toxins are considered to play key roles in the progression of cardiovascular disease (CVD) in CKD. Oxidative stress increases significantly in CKD and accelerates proteinuria and renal dysfunction. In addition, oxidative stress has been reported to induce cardiac hypertrophy and fibrosis. Indoxyl sulfate, a uremic toxin, has recently been suggested to play a crucial role in the development of CVD. Recent in vitro data suggest that indoxyl sulfate increases oxidative stress. Some reports have shown that AST-120, which is an oral charcoal adsorbent, can reduce oxidative stress by lowering serum indoxyl sulfate levels. Recently, we have also demonstrated that indoxyl sulfate is associated with the production of oxidative stress, and that increased oxidative stress is significantly correlated with cardiac hypertrophy and fibrosis. Furthermore, results of our basic and clinical studies suggested that AST-120 can prevent progression of cardiac hypertrophy by reducing oxidative stress in CKD. Thus, one of the main targets of the management of CKD and CVD is the control of oxidative stress and uremic toxins, such as indoxyl sulfate.