Randomized Clinical Trial of Dialysate Cooling and Effects on Brain White Matter

Abstract

Hemodialysis is associated with significant circulatory stress that could produce recurrent and cumulative ischemic insults to multiple organs, such as the brain. We aimed to characterize hemodialysis-induced brain injury by longitudinally studying the effects of hemodialysis on brain white matter microstructure and further examine if the use of cooled dialysate could provide protection against hemodialysis-associated brain injury. In total, 73 patients on incident hemodialysis starting within 6 months were randomized to dialyze with a dialysate temperature of either 37°C or 0.5°C below the core body temperature and followed up for 1 year. Brain white matter microstructure was studied by diffusion tensor magnetic resonance imaging at baseline and follow-up (38 patients available for paired analysis). Intradialytic hemodynamic stress was quantified using the extrema points analysis model. Patients on hemodialysis exhibited a pattern of ischemic brain injury (increased fractional anisotropy and reduced radial diffusivity). Cooled dialysate improved hemodynamic tolerability, and changes in brain white matter were associated with hemodynamic instability (higher mean arterial pressure extrema points frequencies were associated with higher fractional anisotropy [peak r=0.443, P,0.03] and lower radial diffusivity [peak r=20.439, P,0.02]). Patients who dialyzed at 0.5°C below core body temperature exhibited complete protection against white matter changes at 1 year. Our data suggest that hemodialysis results in significant brain injury and that improvement in hemodynamic tolerability achieved by using cooled dialysate is effective at abrogating these effects. This intervention can be delivered without additional cost and is universally applicable.

Effect of Lowering the Dialysate Temperature in Chronic Hemodialysis

“…The study by Eldehni et al (42) shows that hemodialysis results in a significant amount of magnetic resonance imaging changes signifying brain injury that could possibly be alleviated by the use of cold-temperature hemodialysis. Also, Parker et al (41) have found that the use of cold-temperature hemodialysis may improve nocturnal sleep by decreasing sympathetic activation and sustaining the nocturnal skin temperature.…”

Cooling dialysate during in-center hemodialysis: Beneficial and deleterious effects

“…Since that time, it has become apparent that dialysis itself is a hemodynamic stressor [24] which triggers circulatory stress and consequently damages vasculature in the heart, mesentery, and brain [25][26][27] amongst other organs. Two recent trials demonstrated that cooled dialysate imparts a protective effect in these organs.…”

“…Two recent trials demonstrated that cooled dialysate imparts a protective effect in these organs. Eldehni et al [25] hypothesized that ultrastructural injury to the white matter in the brain might be mitigated by cooling dialysate hence reducing dialysis-induced circulatory stress. This was evaluated by randomizing 38 incident dialysis patients to dialyze for 12 mo at either 37 ℃ or 0.5 ℃ below their core body temperature; the latter was determined by averaging each patient's temperature by tympanic thermometer during six sessions prior to commencing the trial.…”

Neurocritical Care for Patients with Kidney Dysfunction

“…Longitudinal studies have shown that reduced blood flow in normal WM predicts development of leukoaraiosis [19], and analysis of almost 3000 participants in the Rotterdam Study demonstrated that lower eGFR is independently associated with lower CBF after adjustment for cardiovascular risk factors [31]. In a UK study, brain MRI and BP variability were analyzed in hemodialysis patients [32]. Although sample size was small (∼20 patients per group), the study demonstrated development of ischemic WM changes on dialysis which were more pronounced in patients with increased intradialytic hemodynamic instability.…”