Mild cognitive impairment and kidney disease: clinical aspects.

Abstract

A link between brain dysfunction and advanced kidney disease was first noted in the 1930s. Terms such as “uremic encephalopathy”, “dialysis disequilibrium syndrome” and “dialysis dementia” were later used to describe impairment of brain function in severe uremic states or during the rapid initiation of early dialysis regimens. Recent data, however, suggest brain damage can be present at earlier stages in chronic kidney disease (CKD), and manifest with a continuum from mild involvement (mild cognitive impairment, MCI) up to clinically relevant dementia. Being a prodromal stage, MCI should be identified and studied before irreversible damage is present. MCI is detectable in up to 30-60% of patients with mild CKD (MCI-CKD). Brain imaging and electrophysiological studies suggest that MCI-CKD represents a more complex clinical entity different in many ways from MCI seen in the general population, which is more often age-related and linked to widespread vascular disease. Moreover, even hemodialysis regimens used today appear unable to prevent MCI-CKD, and may even worsen it, whereas kidney transplantation seems to limit disease progression. This suggests that factors not fully correctable by dialysis, including uncleared “middle molecules”, inadequately controlled hyperparathyroidism or chronic anemia, may contribute to impaired cognition. Furthermore, MCI-CKD is not only related to a reduced glomerular filtration rate (GFR) and/or the presence of albuminuria, but also carries an increased mortality risk. Most current observations are drawn from retrospective data and based on comparisons made across different studies. However, new tools now available in neuroscience (fMRI, brain tractography, two-photon microscopy, high-throughput robotic analysis of neuronal cultures) hold the promise of better insights into the characterization of MCI-CKD, its pathogenesis, and potential biomarkers.