Sodium Accumulation Study in Haemodialysis: Brain Study

Haemodialysis (HD) sustains life in patients with end-stage kidney disease (ESKD) but is associated with a marked increase in cognitive impairment, being three times more common and presenting at a younger age. The predominant features of cognitive impairment associated with HD are loss of executive function, including higher processing such as planning, task prioritisation and self-regulation. The mechanism for development and acceleration of cognitive impairment on dialysis is not well understood, however hypertension and cardiovascular disease are likely to play a significant role, alongside changes in brain perfusion as a result of dialysis itself, which has been shown in a prior study using PET-CT.

Sodium balance is normally regulated by the kidneys in health, but has to be achieved by sodium removal during HD for those with ESKD. Recent evidence suggests that accumulation of sodium in tissue may be a critical factor impacting the development of hypertension and cardiovascular disease (CVD) in patients with ESKD. Non-invasive methods are therefore required to study tissue sodium accumulation in this context.

23Na MRI has the potential to provide complementary quantitative parameters of tissue health, in a non-invasive manner. Sodium homeostasis is central to maintenance of human physiology, providing an index of cellular integrity and energy status. The maintenance of sodium gradients across the cell membrane, by the Na+/K+ ATPase pump, enables 23Na MRI to distinguish between different environments within organs, providing a biomarker of disease status, notably kidney disease, hypertension, and brain disorders.

Previously, traditional proton (1H) magnetic resonance imaging (MRI) in dialysis patients demonstrated a decrease in grey matter T1 and an accompanying increase in white matter T1 when comparing scans before, during and after dialysis, In this context, T1 can be thought of as a marker of water content. This demonstrates that changes in the brain occur as a direct consequence of dialysis, with fluid and sodium shifts across cellular compartments the most likely explanation. This is important, as it suggests a novel mechanism by which dialysis may cause reductions in cognitive function. However, this needs further study to establish these mechanisms with more confidence.

At the SPMIC, a dual tuned proton(1H)/sodium(23Na) volume head RF coil for 23Na imaging of the brain has been installed and interfaced; and imaging methods to perform 23Na MRI of the brain have been optimised.

This study proposes to utilise 23Na MRI of the brain along with proton measures of T1, before and after dialysis within existing experimental set-up at SPMIC. This will provide new insights into the direct effects of dialysis on brain sodium levels, and in turn deepen our understanding of the link between sodium, fluid overload, dialysis and the brain.