Re-Establishing Brain Networks in Patients with ESRD after Successful Kidney Transplantation

Abstract

Background and objectives: Cognition in ESRD may be improved by kidney transplantation, but mechanisms are unclear. We explored patterns of resting-state networks with resting-state functional magnetic resonance imaging among patients with ESRD before and after kidney transplantation.

Design, setting, participants, & measurements: Thirty-seven patients with ESRD scheduled for kidney transplantation and 22 age-, sex-, and education-matched healthy subjects underwent resting-state functional magnetic resonance imaging. Patients were imaged before and 1 and 6 months after kidney transplantation. Functional connectivity of seven resting-state subnetworks was evaluated: default mode network, dorsal attention network, central executive network, self-referential network, sensorimotor network, visual network, and auditory network. Mixed effects models tested associations of ESRD, kidney transplantation, and neuropsychological measurements with functional connectivity.

Results: Compared with controls, pretransplant patients showed abnormal functional connectivity in six subnetworks. Compared with pretransplant patients, increased functional connectivity was observed in the default mode network, the dorsal attention network, the central executive network, the sensorimotor network, the auditory network, and the visual network 1 and 6 months after kidney transplantation (P=0.01). Six months after kidney transplantation, no significant difference in functional connectivity was observed for the dorsal attention network, the central executive network, the auditory network, or the visual network between patients and controls. Default mode network and sensorimotor network remained significantly different from those in controls when assessed 6 months after kidney transplantation. A relationship between functional connectivity and neuropsychological measurements was found in specific brain regions of some brain networks.

Conclusions: The recovery patterns of resting-state subnetworks vary after kidney transplantation. The dorsal attention network, the central executive network, the auditory network, and the visual network recovered to normal levels, whereas the default mode network and the sensorimotor network did not recover completely 6 months after kidney transplantation. Neural resting-state functional connectivity was lower among patients with ESRD compared with control subjects, but it significantly improved with kidney transplantation. Resting-state subnetworks exhibited variable recovery, in some cases to levels that were no longer significantly different from those of normal controls.

Keywords: Attention; Brain; Cognition; Healthy Volunteers; Kidney Failure, Chronic; Magnetic Resonance Imaging; end-stage renal disease; kidney transplantation.

Graphical abstract

Figure 1.

The flowchart of this study. MRI, magnetic resonance imaging.

Figure 2.

Cortical representation of the seven group-level resting-state networks in controls and patient groups by one sample t test. Lateral and medial views of the left hemisphere and lateral and medial views of the right hemisphere are shown for each group. The color scale represents Z value in each resting-state subnetwork (maps are thresholded at P<0.05, AlphaSim corrected). (A) Control group. (B) Prekidney transplantation group. (C) One-month postkidney transplantation group. (D) Six-month postkidney transplantation group.

Figure 3.

Abnormal functional connectivity in six resting-state networks in the patients group compared with normal controls (NCs). Except for in the self-referential network, pretransplantation patients with ESRD show abnormal (mostly decreased) functional connectivity in six subnetworks compared with healthy controls. Compared with controls, patients in the 1-month kidney transplantation group show decreased functional connectivity in the default mode network, the dorsal attention network, the control executive network, the sensorimotor network, and the auditory network. Both increased and decreased functional connectivity were found for the visual network. Six months after kidney transplantation, patients showed both increased and decreased functional connectivity for the sensorimotor network compared with controls. No differences are found for the dorsal attention network, the control executive network, the auditory network, and the visual network. These networks show a gradually improving tendency from prekidney transplantation to 1 month after kidney transplantation to 6 months after kidney transplantation. Z represents Montreal Neurologic Institute coordinates of brain regions. Blue indicates decreased functional connectivity, and red indicates increased functional connectivity, with the amount of blue or red proportional to the magnitude of the difference. Not significant indicates no statistical difference. Pre, prekidney transplantation; 1 m, 1 month after kidney transplantation; 6 m, 6 months after kidney transplantation.

Figure 4.

Increased functional connectivity in patients after kidney transplantation compared with prekidney transplantation. Compared with prekidney transplantation, 1 and 6 months after transplantation, patients showed significantly increased functional connectivity in the default mode network, the dorsal attention network, the control executive network, the sensorimotor network, the auditory network, and the visual network. Compared with 1 month postkidney transplantation, the patients 6 months after kidney transplantation showed significantly increased connectivity for the default mode network, the control executive network, and the auditory network (all P=0.01). For the dorsal attention network, the sensorimotor network, and the visual network, no significant functional connectivity changes are shown between 1 and 6 months after kidney transplantation. Z represents Montreal Neurologic Institute coordinates of brain regions. Blue indicates decreased functional connectivity, and red indicates increased functional connectivity, with the amount of blue or red proportional to the magnitude of the difference. Not significant indicates no statistical difference. Pre, prekidney transplantation; 1 m, 1 month after kidney transplantation; 6 m, 6 months after kidney transplantation.