Altered Resting-State Functional Networks in Nondialysis Patients with Stage 5 Chronic Kidney Disease: A Graph–Theoretical Analysis

This study aimed to investigate the topological characteristics of the resting-state functional network and the underlying pathological mechanism in nondialysis patients with stage 5 chronic kidney disease (CKD5 ND). Eighty-five subjects (21 patients with CKD5 ND, 32 patients with CKD on maintenance hemodialysis (HD), and 32 healthy controls (HCs)) underwent laboratory examinations, neuropsychological tests, and brain magnetic resonance imaging. The topological characteristics of networks were compared with a graph–theoretical approach, and correlations between neuropsychological scores and network properties were analyzed. All participants exhibited networks with small-world attributes, and global topological attributes were impaired in both groups of patients with CKD 5 (ND and HD) compared with HCs (p < 0.05); these impairments were more severe in the CKD5 ND group than in the HD group (p < 0.05). Compared with the HC group, the degree centrality of the CKD5 ND group decreased mainly in the basal ganglia and increased in the bilateral orbitofrontal gyrus, bilateral precuneus, and right cuneus. Correlation analysis showed that the degree of small-worldness, normalized clustering coefficients, and Montreal Cognitive Assessment (MoCA) scores were positively correlated and that characteristic path length was negatively correlated with these variables in patients with CKD5 ND. The nodal efficiency of the bilateral putamen (r = 0.53, p < 0.001 and r = 0.47, p < 0.001), left thalamus (r = 0.37, p < 0.001), and right caudate nucleus (r = 0.28, p = 0.01) was positively correlated with MoCA scores. In conclusion, all CKD5 ND patients exhibited changes in functional network topological properties and were closely associated with mild cognitive impairment. More interestingly, the topological property changes in CKD5 ND patients were dominated by basal ganglia areas, which may be more helpful to understand and possibly reveal the underlying pathological mechanisms of cognitive impairment in CKD5 ND.