Chronic kidney disease (CKD) is associated with an increased risk of cognitive impairment. Patients with CKD display an increased permeability of the blood–brain barrier. Zimmermann et al. highlighted the implication of potassium efflux in the microglia and its activation, the activation of the interleukin-1b/interleukin-1R pathway, linked to blood–brain barrier permeability and cognitive impairment in CKD. Along with uremic toxicity, this study provides new solid insights about pathophysiological mechanisms of cognitive impairment in CKD, and potential therapeutic targets.