Reduced White Matter Integrity in Patients With End-Stage and Non-end-Stage Chronic Kidney Disease: A Tract-Based Spatial Statistics Study.

Yuhan Jiang,Jian Jiang,Yanwei Miao,Yangyingqiu Liu,Qiuyi Gao,Peipei Chang,Weiwei Wang,Yiwei Che,Nan Wang,Liangjie Lin,Qingwei Song,Bingbing Gao

doi:10.3389/fnhum.2021.774236

Abstract

Background and Purpose: Reduced white matter (WM) integrity has been implicated in chronic kidney disease (CKD), especially in end-stage renal disease (ESRD). However, whether the differences in WM abnormalities exist in ESRD and non-end-stage CKD (NES-CKD) remains unclear. Hence, this study aimed to investigate the WM microstructural changes between the two stages using diffusion tensor imaging (DTI) and explore the related influencing factors.Methods: Diffusion tensor imaging’ images were prospectively acquired from 18 patients with ESRD, 22 patients with NES-CKD, and 19 healthy controls (HCs). Tract-based spatial statistics (TBSS) was performed to assess the voxel-wise differences in WM abnormalities among the three groups. The relationships between DTI parameters and biochemical data were also analyzed.Results: Compared with NES-CKDs, FA value was significantly decreased, and AD value increased in ESRDs mainly in brain regions of bilateral anterior thalamic radiation (ATR), the genu and body of corpus callosum (CC), bilateral anterior corona radiata, superior corona radiata, and superior longitudinal fasciculus. Besides, extensive and symmetrical deep WM damages were observed in patients with ESRD, accompanied by increased MD and RD values. Multiple regression analysis revealed that uric acid and serum phosphorus level can be used as independent predictors of WM microstructural abnormalities in clusters with statistical differences in DTI parameters between ESRD and NES-CKD groups.Conclusion: In the progression of CKD, patients with ESRD have more severe WM microstructural abnormalities than NES-CKDs, and this progressive deterioration may be related to uric acid and phosphate levels.

Highlights

Chronic kidney disease (CKD) is defined as decreased kidney function shown by an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m2 or the presence of albuminuria with at least 3-month duration (Zhang L. et al, 2012; Webster et al, 2017)
End-stage renal disease (ESRD) vs. non-end-stage CKD (NES-CKD) We identified three independent clusters with statistically significant differences in fractional anisotropy (FA) and axial diffusivity (AD) values and one independent cluster with a significant difference in mean diffusivity (MD) and radial diffusivity (RD) values between ESRD and NES-CKD groups
We found significantly reduced FA values in the ESRD group compared to the NES-CKD group, mainly in bilateral anterior thalamic radiation (ATR), the genu, and body of CC, bilateral anterior corona radiata (ACR), bilateral superior corona radiata, bilateral IFOF, and left superior longitudinal fasciculus (SLF) (p < 0.05, threshold-free cluster enhancement (TFCE)-corrected, Table 2)

Summary

Introduction

Chronic kidney disease (CKD) is defined as decreased kidney function shown by an estimated glomerular filtration rate (eGFR) of less than 60 ml/min per 1.73 m2 or the presence of albuminuria with at least 3-month duration (Zhang L. et al, 2012; Webster et al, 2017). End-stage renal disease (ESRD) occurs when CKD progresses to the eGFR of < 15 ml/min/1.73 m2. About 10–40% of patients with CKD had impaired cognitive function (Sarnak et al, 2013) and gradually progresses with the decline of kidney function. Patients with ESRD treated with hemodialysis show a 26–60% prevalence of mild cognitive impairment. The neurocognitive decline is most likely to be related to brain structure damage, especially white matter (WM) abnormalities (Vogels et al, 2012). More severe CKD may lead to more severe WM damage, which is associated with cognitive impairment (Liu et al, 2020). WM integrity may be a more suitable biomarker for brain changes in patients with CKD. Reduced white matter (WM) integrity has been implicated in chronic kidney disease (CKD), especially in end-stage renal disease (ESRD). This study aimed to investigate the WM microstructural changes between the two stages using diffusion tensor imaging (DTI) and explore the related influencing factors

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Conclusion