Acute kidney injury (AKI) is characterized by an abrupt decline in kidney function associated with increased creatinine levels or reduction in urine output.1 Although AKI is mostly reversible and kidney function may return to baseline after initial insult, it is now known that AKI is not innocent and portends increased risk of long-term complications.2 Indeed, AKI has been shown to be a risk factor for chronic kidney disease (CKD),3 stroke,4 and heart disease.5 In addition, previous studies showed that AKI is also risk factor cognitive dysfunction,6 delirium,7 and dementia.8,9 Furthermore, a meta-analysis demonstrated that higher dementia risk was observed in AKI patients compared to patients without AKI after adjustment of covariates (RR: 1.92) although the strength of the evidence was low. Importantly, the same meta-analysis showed that all-cause mortality was higher in AKI patients with dementia than patients without AKI (RR:2.11).10 A more recent meta-analysis also showed that patients with AKI had higher risk of cognitive impairment or dementia compared to those without AKI (OR:1.87).6 On the other hand, a retrospective small scale study showed that cognitive function did not differ with different severity of AKI.11

It is well-known that during AKI, pathologic pathways are activated by damaged kidney which have detrimental effects to distant organs.12 Kidney-brain crosstalk is one of the example of these interactions.13 During AKI, brain dysfunction and brain damage occurs via kidney-induced proinflammatory cytokine secretion, oxidative stress, and dysregulation of sodium, potassium, and water channels.14 In addition, accumulation of uremic toxins and change in osmolarity play a role in brain dysfunction and cognitive impairment after AKI.15 Experimental studies showed that ischemia induced AKI engender microgliosis, pyknosis, inflammation, disruption of blood brain barrier (BBB) and decreased locomotor activity.16 Furthermore, formation of reactive oxygen species increases during AKI,17 which increases permeability of the BBB leading to ischemia-reperfusion injury, brain edema, and hemorrhage.18 Importantly, these alterations which occur during AKI can induce long term irreversible functional and structural brain damage.19,20 As cognitive dysfunction and dementia have both individual and population-level impacts,21 it is very important to highlight the factors related with increased risk for future dementia and cognitive decline after AKI. In this context, it is important to know if AKI; is a real risk factor future dementia and cognitive decline.

Based on aforementioned data, we first summarized the existing data regarding the relationship between AKI and long-term cognitive decline or dementia. Second, we explained the potential mechanisms regarding the AKI-induced brain damage and detrimental alterations. Lastly, we highlighted the unknowns and potential future study subjects regarding AKI, cognitive dysfunction or dementia.