Research Article: A preliminary report of longitudinal white matter alterations in patients with end-stage renal disease: A three-year diffusion tensor imaging study

Date Published: April 30, 2019

Publisher: Public Library of Science

Author(s): Ming-Chung Chou, Chih-Hung Ko, Tsyh-Jyi Hsieh, Jer-Ming Chang, Wei-Shiuan Chung, Linda Chao.


End-stage renal disease (ESRD) patients exhibit silent white-matter alterations after long-term hemodialysis, which may be due to ESRD itself or the hemodialysis. The purpose of this study was to investigate the longitudinal white-matter alterations in the ESRD patients under 3-year long-term hemodialysis using voxel-wise analysis of diffusion tensor imaging (DTI).

15 ESRD patients and 15 age-matched healthy controls participated in this study. Due to the development of abnormal brain lesions in some cases, 13 ESRD patients and 13 age-matched healthy controls were enrolled and underwent cognitive function assessment and DTI acquisition at two-time points separated by 3 years. Voxel-based analysis was performed to globally detect white-matter alterations between the two groups as well as between the two scans within the two groups.

In the ESRD patients, diffusivity indices were significantly increased and the fractional anisotropy was significantly decreased in both scans, as compared with healthy controls. Longitudinal comparisons showed significant white-matter alterations in healthy controls in three years, but little or no significant alterations were noted in the ESRD patients after additional 3-year hemodialysis.

Poorer white matter integrity and cognitive function are noted in ESRD patients and the toxic effect of ESRD may be the major factor of white matter alterations.

Partial Text

End-stage renal disease (ESRD) is defined as the final stage of chronic kidney disease, with a permanent loss of >90% of normal renal function [1]. In the ESRD patients, urea and toxic metabolites are accumulated in the blood and tissues, which in turn leads to multiple organ dysfunction. In recent years, hemodialysis has been the most common treatment to remove excess metabolic waste from the body. However, the ESRD patients on dialysis may still develop uremic neuropathies such as osmotic demyelination syndrome, dialysis disequilibrium syndrome, and cerebrovascular diseases [2–4]. Thus, it is important to monitor changes in the brain tissue in such patients.

To the best of our knowledge, this is the first study using a voxel-based DTI analysis to assess longitudinal alterations in white-matter tissue in both ESRD patients and healthy subjects over a 3-year period. Consistent with previous findings [8, 9, 17–19], the declines of the cognitive functions with associated alterations of the DTI indices were noted the ESRD patients. However, the longitudinal follow-up showed that the ESRD patients had no more interval changes of the DTI indices than the healthy controls. The findings suggest that the DTI indices in the ESRD patients undergoing regular hemodialysis were in a relatively stable condition, as the healthy controls.

In the cross-sectional DTI analysis, white matter integrity was significantly lower in the ESRD patients than in the healthy controls; however, in the longitudinal voxel-based DTI analysis, less white-matter alterations were noted in the ESRD patients than that in healthy participants after a 3-years follow-up. In conclusion, poorer white matter integrity and cognitive function are noted in ESRD patients. The toxic effect of ESRD may be the major factor for white matter alterations in the ESRD patients, but 3-year regular hemodialysis did not cause significant white matter alterations.