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Clinical Investigation

Brain Functional Connectivity Is Reduced in Pediatric Chronic Kidney Disease

Friday, September 19, 2025
10:00 AM - 10:15 AM CT
Location: Ann & Robert H. Lurie Children’s Hospital of Chicago, 11th Floor Conference Room 200 E. Superior
Disclosure(s):
Ryan C. Ward, MD, MS: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Emily J. Steinbach, PhD: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Background: Pediatric patients with chronic kidney disease (CKD) often experience declines in kidney function during critical neurodevelopmental stages. Structural MRI studies have revealed focal reductions in cerebellar gray matter and globally decreased white matter integrity. These changes may impact brain connectivity. Functional connectivity (FC) involves the coordinated activation of distinct brain regions, measured by the BOLD signal on resting state functional MRI (rs-fMRI). Seven major functional brain networks have been identified, each playing a vital role in cognitive function. However, the effects of CKD on these functional networks are largely unexplored.

Objectives: To investigate the relationship between resting state brain FC and kidney function in pediatric patients with CKD.

Design/Methods: We recruited pediatric CKD patients (stages 1-3, non-dialysis, non-transplant) with congenital anomalies of the kidneys and urinary tract and healthy controls. Rs-fMRI was performed on a 3T MRI scanner. Estimated glomerular filtration rate (eGFR), was quantified using the CKiD U25 equation. Connectivity analyses utilized seed-based approaches focusing on cerebellar connectivity to major brain networks. FC measures were used as outcome variables in models including kidney function and group as independent variables.

Results: 37 CKD patients (mean age 12.4 ± 4.1 years; 81% male) and 87 healthy controls (mean age 13.0 ± 4.7 years; 51% male) were included. eGFR was significantly lower in the CKD group (71 mL/min/1.73m2 compared to 101 mL/min/1.73m2 in controls, p< 0.001) When adjusting for hemoglobin, age, sex, and socioeconomic status, group differences in network connectivity trended toward significance in default mode network to dorsal attention network (DAN) connectivity (p = 0.06) and default mode network to salience network (p = 0.09) whereby inter-network connectivity was lower in the CKD group. In adjusted models, lower eGFR was associated with impaired connectivity in the cerebellum to DAN pathway (p = 0.02, Figure 1) and cerebellum to salience network pathway (p = 0.04, Figure 2).

Conclusions: Kidney function is associated with altered brain FC in pediatric CKD. Impaired connectivity between the cerebellum and key cognitive networks suggests that reduced kidney function may disrupt critical neurodevelopmental processes. Future studies should explore the mechanisms underlying these connectivity changes, with particular attention to the impact of advanced CKD and kidney transplantation on connectivity.