Regional Cerebral Blood Flow in Children and Young Adults with Chronic Kidney Disease

Abstract

Purpose To investigate the pathophysiologic effects of chronic kidney disease (CKD) on brain function in children with CKD by correlating cerebral blood flow (CBF) with clinical and behavioral indexes. Materials and Methods In this prospective study, 73 pediatric patients with CKD (mean age, 15.80 years ± 3.63; range, 9-25 years) and 57 control subjects (mean age, 15.65 years ± 3.76; range, 9-25 years) were recruited. CBF measurements were acquired with an MRI arterial spin labeling scheme. Neurocognitive measurements were performed with traditional and computerized neurocognitive batteries. Clinical data were also collected. Group-level global and regional CBF differences between patients with CKD and control subjects were assessed. Regression analyses were conducted to evaluate the associations among regional CBF, clinical variables, and cognitive performance. Results Patients with CKD showed higher global CBF compared with control subjects that was attributable to reduced hematocrit level (mean, 60.2 mL/100 g/min ± 9.0 vs 56.5 mL/100 g/min ± 8.0, respectively). White matter CBF showed correlation with blood pressure (r = 0.244, P = .039), a finding suggestive of altered cerebrovascular autoregulation. Regional CBF differences between patients and control subjects included regions in the "default mode" network. In patients with CKD, positive extrema in the precuneus showed a strong correlation with executive function (ρ = 0.608, P = .001). Conclusion Systemic effects of estimated glomerular filtration rate, hematocrit level, and blood pressure on CBF and alterations in regional CBF may reflect impaired brain function underlying neurocognitive symptoms in CKD. These findings further characterize the nature of alterations in brain physiologic features in children, adolescents, and young adults with CKD.

Figure 1:

Voxel-wise group comparison of cerebral blood flow (CBF) after removal of effects of hematocrit level, age, and sex. Contrast shown demonstrates regions where CBF in patients with chronic kidney disease (CKD) is greater than that in control subjects. There were no regions where control subjects showed greater CBF than patients with CKD. Color bar indicates t scores. x, y, z = coordinates in Montreal Neurological Institute (MNI) space.

Figure 2a:

Images show overlapped clusters from all individual patients with chronic kidney disease with positive extrema in cerebral blood flow (CBF) in subject-specific voxel-wise analysis. Color bar indicates total number of subjects who had subject-specific clusters with increased CBF. x, y, z = coordinates in Montreal Neurological Institute (MNI) space.

Figure 2b:

Images show overlapped clusters from all individual patients with chronic kidney disease with positive extrema in cerebral blood flow (CBF) in subject-specific voxel-wise analysis. Color bar indicates total number of subjects who had subject-specific clusters with increased CBF. x, y, z = coordinates in Montreal Neurological Institute (MNI) space.

Figure 2c:

Images show overlapped clusters from all individual patients with chronic kidney disease with positive extrema in cerebral blood flow (CBF) in subject-specific voxel-wise analysis. Color bar indicates total number of subjects who had subject-specific clusters with increased CBF. x, y, z = coordinates in Montreal Neurological Institute (MNI) space.

Figure 2d:

Images show overlapped clusters from all individual patients with chronic kidney disease with positive extrema in cerebral blood flow (CBF) in subject-specific voxel-wise analysis. Color bar indicates total number of subjects who had subject-specific clusters with increased CBF. x, y, z = coordinates in Montreal Neurological Institute (MNI) space.

Figure 3:

Scatter plot shows partial residual values of precuneus cerebral blood flow (CBF) and executive function in patients with chronic kidney disease with presence of positive extrema CBF, indicating significant correlation between precuneus CBF and executive function after controlling for hematocrit (HCT), age, and sex (ρ = 0.608, P = .001). TNB = traditional neurocognitive battery.