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=-0.439, 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.

Keywords: BP; cardiovascular; hemodialysis.

Copyright © 2015 by the American Society of Nephrology.

Figures

Figure 1.

Trial flow chart. Consolidated Standards of Reporting Trials (CONSORT) flow diagram demonstrating the phases of the trial starting from screening through to enrolment, randomization, follow up and data analysis.

Figure 2.

Statistical image representing the results of the tract-based spatial statistical test comparing FA with RD at baseline and 1 year by aggregating the control and intervention groups. The statistically significant voxels with P values<0.05 corrected for multiple comparisons (red-yellow) are presented on a mean skeleton (green) on standardized T1 axial brain slices (of z scores). The color bar represents the degree of significance. The box plots represent FA and RD values in the statistically significant voxels at baseline and 1 year with the two groups aggregated.

Figure 3.

Statistical image representing the results of the voxel-wise statistical model for the change in FA in each group over 1 year. The statistically significant voxels with P values<0.05 corrected for multiple comparisons (red-yellow) are overlaid on a mean skeleton (green) on standardized T1 axial brain slices (of z scores). The color bar represents the degree of significance. The box plots represent FA values of the statistically significant voxels in the group that dialyzed at 37°C at baseline and 1 year. No statistically significant voxels were found in the group that dialyzed at 0.5°C below their body temperature. In this group, FA values of the voxels with the same location as the significant ones in the control group are represented by the box plots at the bottom.

Figure 4.

A graphical representation of repeated measures ANOVA of the frequencies of the mean arterial BP extrema points across all groups at baseline and follow-up. The circles represent the means of the frequencies of the extrema points for mean arterial BP. The lines represent confidence intervals.