Oxidative stress and endoplasmic reticulum stress in kidney aging: Impact of uremic toxins as the cause of stress

Abstract

Population aging continues all over the world. Kidney aging is a major factor in the development and progression of chronic kidney disease (CKD), which shows premature phenotypic changes. Kidney aging associated with a decline in kidney function affects the functions of remote organs (heart, blood vessels, and brain), and CKD is a significant risk factor in cardiovascular disease (CVD) and stroke, both of which are age-related diseases. This association strongly indicates that kidney aging accelerates the aging of remote organs and that the kidney is a central organ in the maintenance of life. Recent studies of the pathophysiology of CKD emphasize the contribution of endoplasmic reticulum (ER) stress and the link between ER stress and other pathogenic stresses such as oxidative stress and glycative stress, both of which are known to lead to premature aging. In particular, uremic toxins have received attention as causal factors of a vicious cycle of these stress signals, resulting in progression of CKD, rather than being a consequence of CKD. This article summarizes the impact and pathophysiological significance of oxidative stress and glycative stress, and ER stress. It also discusses the crosstalk of these stresses, novel evidence regarding uremic toxins as inducers of these stresses, and finally the contribution of these stresses to kidney premature aging.