Topological disruptions of metabolic brain networks in early-stage chronic kidney disease

Although previous arterial spin labeling (ASL) studies have characterized cerebral perfusion alterations in chronic kidney disease (CKD), it remains unclear whether these changes reflect disrupted coordination of metabolic activity at the network level. Therefore, this study aimed to investigate the topological alterations of individual-level metabolic brain networks in patients with early-stage CKD. A total of 52 patients with early-stage CKD and 53 matched healthy controls (HCs) underwent ASL magnetic resonance imaging of the brain. Individual-level metabolic brain networks were constructed by estimating the interregional similarities of cerebral blood flow (CBF) probability distributions using the Kullback-Leibler divergence (KLD) measure. Compared with HCs, patients with early-stage CKD exhibited significantly increased clustering coefficient (p = 0.001) and local efficiency (p = 0.005) in their metabolic brain networks. The early-stage CKD group showed aberrant nodal degree, nodal efficiency, and nodal betweenness mainly in the frontal lobe, occipital lobe, and hippocampus. In terms of modular connectivity, compared with HCs, intermodular connectivity between the sensorimotor network and frontoparietal network significantly increased in early-stage CKD group (p = 0.004). None of these aberrant topological properties showed significant correlations with Montreal Cognitive Assessment (MoCA) scores or laboratory indices after FDR correction. Our findings indicated that topological disruptions of metabolic brain networks can be detected in early-stage CKD. These network abnormalities may provide complementary insights into the neural mechanisms underlying early brain vulnerability in CKD.