Brain Magnetic Resonance Imaging Findings in Children and Young Adults With CKD.

BACKGROUND: The neuroanatomic basis for cognitive impairment in chronic kidney disease (CKD) is incompletely characterized. We performed advanced quantitative structural magnetic resonance imaging (MRI) to determine whether CKD affects brain structure and whether poorer neurocognitive performance in CKD is associated with structural brain differences. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 85 individuals with CKD stages 2 to 5 and 63 healthy controls, aged 8 to 25 years PREDICTORS: CKD versus control, estimated glomerular filtration rate (eGFR), and kidney transplant status were analyzed as predictors of MRI findings. MRI volumes in 19 prespecified regions of gray matter (GM), white matter (WM), and cerebrospinal fluid were analyzed as predictors of neurocognitive performance (median z scores) in 7 prespecified domains. OUTCOMES: 19 prespecified brain regions of interest (ROIs) in 7 prespecified domains. Neurocognitive performance in 7 prespecified domains. MEASUREMENTS: ROI volumes were compared in CKD versus controls using unadjusted t tests and analysis of covariance (ANCOVA). Associations of ROI volumes with eGFR and kidney transplant status in participants with CKD were analyzed using ANCOVA and linear regression. Associations of neurocognitive performance and ROI volumes were analyzed by linear regression. RESULTS: Participants with CKD had lower whole-brain, cortical, and left parietal GM volumes than controls in unadjusted analyses, but no differences were found in adjusted analysis. In participants with CKD, lower eGFR was associated with higher WM volume in whole-brain (P=0.05) and frontal (P=0.04) ROIs, but differences were not significant after multiple comparisons correction. Kidney transplant recipients had lower GM volumes in whole-brain (P=0.01; Q=0.06), frontal (P=0.02; Q=0.08), and left and right parietal (P=0.01; Q=0.06; and P=0.03; Q=0.1) ROIs and higher whole-brain WM volume (P=0.04; Q=0.1). Neurocognitive performance in the CKD group was not associated with ROI volumes. LIMITATIONS: Unable to assess changes in brain structure and kidney function over time; analysis limited to prespecified ROIs and neurocognitive domains. CONCLUSIONS: CKD in children and young adults may be associated with lower GM and higher WM volumes in some ROIs. Differences were relatively subtle in the CKD group as a whole, but were more prominent in recipients of a kidney transplant. However, neurocognitive performance was not explained by differences in brain ROI volumes, suggesting a functional rather than structural basis for neurocognitive impairment in CKD.

Design and methods of the NiCK study: neurocognitive assessment and magnetic resonance imaging analysis of children and young adults with chronic kidney disease.

BACKGROUND: Chronic kidney disease is strongly linked to neurocognitive deficits in adults and children, but the pathophysiologic processes leading to these deficits remain poorly understood. The NiCK study (Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease) seeks to address critical gaps in our understanding of the biological basis for neurologic abnormalities in chronic kidney disease. In this report, we describe the objectives, design, and methods of the NiCK study. DESIGN/METHODS: The NiCK Study is a cross-sectional cohort study in which neurocognitive and neuroimaging phenotyping is performed in children and young adults, aged 8 to 25 years, with chronic kidney disease compared to healthy controls. Assessments include (1) comprehensive neurocognitive testing (using traditional and computerized methods); (2) detailed clinical phenotyping; and (3) multimodal magnetic resonance imaging (MRI) to assess brain structure (using T1-weighted MRI, T2-weighted MRI, and diffusion tensor imaging), functional connectivity (using functional MRI), and blood flow (using arterial spin labeled MRI). Primary analyses will examine group differences in neurocognitive testing and neuroimaging between subjects with chronic kidney disease and healthy controls. Mechanisms responsible for neurocognitive dysfunction resulting from kidney disease will be explored by examining associations between neurocognitive testing and regional changes in brain structure, functional connectivity, or blood flow. In addition, the neurologic impact of kidney disease comorbidities such as anemia and hypertension will be explored. We highlight aspects of our analytical approach that illustrate the challenges and opportunities posed by data of this scope. DISCUSSION: The NiCK study provides a unique opportunity to address key questions about the biological basis of neurocognitive deficits in chronic kidney disease. Understanding these mechanisms could have great public health impact by guiding screening strategies, delivery of health information, and targeted treatment strategies for chronic kidney disease and its related comorbidities.

Systematic review of structural and functional neuroimaging findings in children and adults with CKD.

CKD has been linked with cognitive deficits and affective disorders in multiple studies. Analysis of structural and functional neuroimaging in adults and children with kidney disease may provide additional important insights into the pathobiology of this relationship. This paper comprehensively reviews neuroimaging studies in both children and adults. Major databases (PsychLit, MEDLINE, WorldCat, ArticleFirst, PubMed, Ovid MEDLINE) were searched using consistent search terms, and studies published between 1975 and 2012 were included if their samples focused on CKD as the primary disease process. Exclusion criteria included case reports, chapters, and review articles. This systematic process yielded 43 studies for inclusion (30 in adults, 13 in children). Findings from this review identified several clear trends: (1) presence of cerebral atrophy and cerebral density changes in patients with CKD; (2) cerebral vascular disease, including deep white matter hyperintensities, white matter lesions, cerebral microbleeds, silent cerebral infarction, and cortical infarction, in patients with CKD; and (3) similarities in regional cerebral blood flow between patients with CKD and those with affective disorders. These findings document the importance of neuroimaging procedures in understanding the effect of CKD on brain structure, function, and associated behaviors. Results provide a developmental linkage between childhood and adulthood, with respect to the effect of CKD on brain functioning across the lifespan, with strong implications for a cerebrovascular mechanism contributing to this developmental linkage. Use of neuroimaging methods to corroborate manifest neuropsychological deficits or perhaps to indicate preventive actions may prove useful to individuals with CKD.