This study was conducted in order to investigate the topological organization of functional and structural brain networks in diabetic kidney disease (DKD) and its potential clinical relevance. Two hundred two subjects (62 DKD patients, 60 diabetes mellitus [DM] patients, and 80 healthy controls) underwent laboratory examination, neuropsychological test, and magnetic resonance imaging (MRI). Large-scale functional and structural brain networks were constructed and graph theoretical network analyses were performed. The effect of renal function on brain functional and structural networks in DKD patients was further evaluated. Correlations were performed between network properties and neuropsychological scores and clinical variables. Progressing deteriorated global and local network topology organizations (especially for functional network) were observed for DKD patients compared with control subjects (all p < 0.05, Bonferroni-corrected), with intermediate values for the patients with DM. DKD patients showed normally appearing functional-structural coupling compared with controls, while DM patients manifested functional-structural decoupling (p < 0.05, Bonferroni-corrected). Impaired kidney function markedly affected functional and structural network organization in DKD patients (all p < 0.05). Urea nitrogen correlated with global and local efficiency in the structural networks (r = - 0.551, p < 0.001; r = - 0.476, p < 0.001, respectively). Global and local efficiency in the structural networks and normalized characteristic path length in the functional networks were associated with information processing speed and/or psychomotor speed. DKD patients showed enhanced functional and structural brain network disruption and normally appearing functional-structural coupling compared with DM patients, which correlated with kidney function, renal toxins, and cognitive performance. • DKD patients showed markedly disrupted functional and structural brain network efficiency measures compared with DM patients and healthy controls. • Reduced kidney function clearly deteriorated functional and structural brain networks in DKD patients. • DKD patients displayed normally appearing functional-structural coupling compared with DM patients.
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