Altered long- and short-range functional connectivity in the patients with end-stage renal disease: a resting-state functional MRI study

To investigate alterations of functional connectivity density (FCD) in patients with end-stage renal disease (ESRD) by using resting-state functional magnetic resonance imaging (rs-fMRI). Medical research ethics committee approval from Jinling hospital and written informed consent from each subject were obtained. Forty six patients with ESRD, consisting of 21 patients minimal nephrotic encephalopathy (MNE) and 25 non-nephro-encephalopathy (non-NE), as well as 23 healthy controls underwent rs-fMRI. Neuropsychological tests were performed in all subjects, while laboratory tests were performed in ESRD patients. A voxel-wise whole brain functional connectivity analysis was used to generate long- and short-range FCD maps. The maps among MNE, non-NE, and healthy controls groups were compared by using one-way analysis of variance tests. A multiple regression analysis was performed to evaluate the correlations between FCD and the variables of neuropsychological or laboratory tests. Compared with healthy controls, non-NE showed decreased long-range FCD mainly in parietal lobe. Moreover, MNE showed further decreased long-range FCD in bilateral middle prefrontal cortex (MPFC), anterior cingulate cortex (ACC) and right superior frontal gyrus. Meanwhile, non-NE showed decreased short-range FCD mainly in frontal cortex, and further reduction in bilateral ACC and right superior parietal gyrus in MNE. In addition, patients with ESRD mainly exhibited increased long-range FCD in left temporal lobe and caudate; and increased short-range FCD in bilateral orbitofrontal cortex and temporal gyri ( P < 0.05, AlphaSim corrected). The number connection test type A score, serum creatinine, urea, and dialysis duration showed negative correlation with FCD in some brain regions, while the digital symbol test scores positively correlated with short-range FCD in left inferior parietal lobule (all P < 0.05, AlphaSim corrected). The prominent long- and short-range FCD reduction was found mainly in default mode network (DMN) and bilateral frontal and parietal lobes, while the progressively decreased long- and short-range FCD in ACC/MPFC and the long-range FCD in left superior frontal gyrus from non-NE to MNE was associated with cognition dysfunction in ESRD patients.