Structural and functional brain alterations in end stage renal disease patients on routine hemodialysis: a voxel-based morphometry and resting state functional connectivity study.

Yingwei Qiu,Xiaofei Lv,Junzhang Tian,Guihua Jiang,Huanhuan Su,Cheng Li,Satoru Hayasaka

doi:10.1371/journal.pone.0098346

Abstract

Background and PurposeCognitive impairment is a well-described phenomenon in end-stage renal disease (ESRD) patients. However, its pathogenesis remains poorly understood. The primary focus of this study was to examine structural and functional brain deficits in ESRD patients.Materials and MethodsThirty ESRD patients on hemodialysis (without clinical neurological disease) and 30 age- and gender-matched control individuals (without renal or neurological problems) were recruited in a prospective, single-center study. High-resolution structural magnetic resonance imaging (MRI) and resting state functional MRI were performed on both groups to detect the subtle cerebral deficits in ESRD patients. Voxel-based morphometry was used to characterize gray matter deficits in ESRD patients. The impact of abnormal morphometry on the cerebral functional integrity was investigated by evaluating the alterations in resting state functional connectivity when brain regions with gray matter volume reduction were used as seed areas.ResultsA significant decrease in gray matter volume was observed in ESRD patients in the bilateral medial orbito-prefrontal cortices, bilateral dorsal lateral prefrontal cortices, and the left middle temporal cortex. When brain regions with gray matter volume reduction were used as seed areas, the integration was found to be significantly decreased in ESRD patients in the fronto-cerebellum circuits and within prefrontal circuits. In addition, significantly enhanced functional connectivity was found between the prefrontal cortex and the left temporal cortex and within the prefrontal circuits.ConclusionsOur study revealed that both the structural and functional cerebral cortices were impaired in ESRD patients on routine hemodialysis.

Highlights

End stage renal disease (ESRD) is the last stage of chronic kidney disease (CKD), and corresponds to complete or almost complete loss of kidney function
When brain regions with gray matter volume reduction were used as seed areas, the integration was found to be significantly decreased in end-stage renal disease (ESRD) patients in the fronto-cerebellum circuits and within prefrontal circuits
Our study revealed that both the structural and functional cerebral cortices were impaired in ESRD patients on routine hemodialysis

Summary

Introduction

End stage renal disease (ESRD) is the last stage (stage 5) of chronic kidney disease (CKD), and corresponds to complete or almost complete loss of kidney function. Conventional MR and computed tomography (CT) imaging studies with visual assessment and manual measurements of structures of interest have demonstrated that patients with ESRD have reduced brain volumes, reduced deep white matter volumes, a high prevalence of subcortical white matter lesions, and a high incidence rate for stroke [5,6,7,8]. MR spectroscopy (MRS) studies have demonstrated that CKD patients (stage 4–5) without clinical signs of uremic encephalopathy showed metabolic disturbances in multiple brain regions, including the parieto-occipital white matter, the occipital grey matter, the basal ganglia and the pons [8,9,10]. The primary focus of this study was to examine structural and functional brain deficits in ESRD patients

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Discussion

Conclusion