The Brain Kidney Axis Vascular Cross Talk

Abstract

AbstractChronic kidney disease (CKD) is associated with cognitive impairment and dementia; 87% of patients on chronic dialysis have some degree of cognitive impairment. The prevalence of CKD increases with age and approximately 40% of persons aged >60 years have CKD. With increasing life expectancy, prevalence of both CKD and dementia are expected to increase.CKD and Alzheimer’s disease (AD) share common risk factors. Patients with CKD are older, and have multiple comorbidities such as hypertension, diabetes mellitus, dyslipidemia, metabolic syndrome, and obesity, making CKD a model for accelerated aging, inflammation, and vascular dysregulation. Inflammation and vascular dysregulation can disrupt blood brain barrier, decreased kidney function can influence amyloid clearance, an important AD biomarker. Patients with CKD have alterations in cerebral blood flow, brain white matter integrity, brain neurochemicals, and blood brain barrier permeability‐ findings that are similar to those seen in AD.We investigated brain alterations seen in CKD before and after successful kidney transplant and found reversibility of brain alterations, and improvement in cognitive function after kidney transplantation. Further, we examined whether the cognitive impairment in CKD is due to comorbidities such as hypertension or due to decreased kidney function. In addition, for the first time, we have shown evidence for disruption of blood brain barrier in patients with CKD. With the high prevalence of CKD in the older population, and the strong association between decreased glomerular filtration rate and cognitive impairment, understanding the mechanisms underlying cognitive impairment and developing strategies to mitigate the risks in the CKD population is important.The potential reversibility in brain alterations seen in CKD after a kidney transplant indicate an opportunity to develop strategies for management of cognitive impairment.