“…Our ER stress monitoring studies converge toward the concept that adaptive cellular responses that are engaged very early after an ischemic insult are required to protect against tissue damage (notably, cell death and tissue remodeling), and individuals who, for as yet unknown reasons, are not able to mount a robust adaptive response are less protected against AKI and have a worse renal prognosis. This concept is consistent with the “preconditioning” hypothesis in which repeated small insults (including those that promote ER stress ( Inagi et al, 2008 , Liu et al, 2016 , Usuki et al, 2013 )) prior to a major injury may afford protection to the target tissue, in part because adaptive responses are already engaged ( Hertzberg et al, 2017 , Stokfisz et al, 2017 ). An understanding of the ability to activate these early responses is critical to correctly identify individuals at risk, which is likely due to complex interactions between intrinsic factors (e.g., genetic and epigenetic factors), acquired structural lesions (e.g., CKD), and environmental triggers (the nature, intensity and duration of the stressor).…”