Altered white matter microstructure mediates the relationship between hemoglobin levels and cognitive control deficits in end-stage renal disease patients

The brain–kidney crosstalk theory suggested that the brain and kidneys may be considered end organs on parallel trajectories and subject to shared risk factors, which are receiving increasing attention. Cognitive control deficits were frequently presented in patients with end-stage renal disease (ESRD). Whether or not cognitive control impairment is concerned with brain–kidney crosstalk is in need of further research. To detect the relationship between ESRD and cognitive control impairment, diffusion tensor imaging was collected in 64 healthy controls (HCs) and 64 patients with ESRD. Tract-based spatial statistics and fixel-based analysis were used to detect the difference of white matter (WM) microstructure and morphology between ESRD patients and HCs in the whole brain. Tractography atlas-based analysis was also used to investigate the difference of diffusional characteristics along fiber bundles of interest between the two groups. For the whole-brain analysis, ESRD patients showed WM microstructural alteration and fiber density variation in the cingulum. In addition, ESRD patients exhibited higher MD and RD than HCs along the anterior cingulum. Among all of the blood biochemistry tests that represent kidney disease to a degree, the stepwise regression analysis showed that only hemoglobin significantly contributed to the cognitive control deficits in ESRD patients. Mediation analysis proved that the relationship between hemoglobin and cognitive control deficits of ESRD patients was mediated by WM microstructural alteration of the cingulum. Our results indicated that the anterior cingulum was correlated with cognitive control deficits and mediated the impact of hemoglobin on cognitive control.