Abstract

End-stage renal disease (ESRD) patients on maintenance haemodialysis (HD) often have damage to brain white matter (WM) and cognitive impairment. However, whether this damage is caused by maintenance HD or renal dysfunction is unclear. Herein we investigate the natural progression of WM damage in patients with ESRD and the effects of HD on WM using tract-based spatial statistics (TBSS) and fixel-based analysis (FBA). Eighty-one ESRD patients, including 41 with no dialysis (ND) and 40 on HD, and 46 healthy controls (HCs) were enrolled in this study. The differences in WM among the three groups [ESRD patients with HD (ESRD-HD), ESRD patients without HD (ESRD-ND) and HCs] were analysed using TBSS and FBA. Pairwise comparison was then used to compare the differences in WM between two groups. The relationships between WM and neurocognitive assessments/clinical data were analysed in ESRD patients with and without HD. The damage to WM in ESRD-ND and ESRD-HD appeared around the lateral ventricles in TBSS, while FBA reflected that the changes had extended to adjacent WM in the anterior hemisphere, with a larger region in ESRD-HD compared with ESRD-ND and the brainstem was also widely affected in ESRD-HD. The Montreal Cognitive Assessment (MoCA) scores were lower in the ESRD-HD group. RD in the body of the corpus callosum were negatively correlated with MoCA scores in both groups. Fiber density and cross-section (FDC) in the left thalamo-prefrontal projection (T_PREFL) and left and right cingulum (CGL and CGR) were positively correlated with MoCA scores in both groups. Creatinine (Cr) was positively correlated with FDC in some frontal projection fibres in the striatum and thalamus, CG and fronto-pontine tract and was positively correlated with FD mainly in premotor projection fibres in the striatum and thalamus in the ESRD-HD group. Cr was negatively correlated with mean and radial diffusivity in regions of the corona radiata in the ESRD-ND group. FBA is more sensitive in detecting differences between ESRD patients and HCs. When ESRD patients receive maintenance HD, the degree of WM damage may not be aggravated, but the range of damaged WM may be expanded, especially in the anterior hemisphere and brainstem. Some of these changes in the anterior hemisphere may contribute to cognitive decline.

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