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Brain abnormalities in children and adolescents with chronic kidney disease.

ABSTRACT: BACKGROUND:Chronic kidney disease (CKD) is a risk factor for vascular disease and stroke. The spectrum of brain injury and microstructural white matter abnormalities in children with CKD is largely unknown. METHODS:Cross sectional study at two North American pediatric hospitals. A cohort of 49 children, 29 with CKD, including renal transplant (mean age 14.4?±?2.9 years; range 9-18), and 20 healthy controls (mean age 13.7?±?3.1 years; range 9-18) had their conventional brain magnetic resonance images (MRIs) reviewed by one neuroradiologist to determine the prevalence of brain injury. Fractional anisotropy (FA) maps calculated from diffusion tensor imaging (DTI) were generated to compare white matter microstructure in CKD compared to controls, using tract-based spatial statistics (TBSS). RESULTS:Focal and multifocal white matter injury was seen on brain MRI in 6 children with CKD (21%). Relative to controls, CKD subjects showed reduced white matter fractional anisotropy and increased mean diffusivity and radial diffusivity in the anterior limb of the internal capsule, suggestive of abnormal myelination. CONCLUSION:Cerebral white matter abnormalities, including white matter injury, are under-recognized in pediatric CKD patients. Brain imaging studies through progression of CKD are needed to determine the timing of white matter injury and any potentially modifiable risk factors.

SUBMITTER: Matsuda-Abedini M

PROVIDER: S-EPMC6258313 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Brain abnormalities in children and adolescents with chronic kidney disease.

Matsuda-Abedini Mina M Fitzpatrick Kevin K Harrell Waverly R WR Gipson Debbie S DS Hooper Stephen R SR Belger Aysenil A Poskitt Ken K Miller Steven P SP Bjornson Bruce H BH

Pediatric research 20180702 3

<h4>Background</h4>Chronic kidney disease (CKD) is a risk factor for vascular disease and stroke. The spectrum of brain injury and microstructural white matter abnormalities in children with CKD is largely unknown.<h4>Methods</h4>Cross sectional study at two North American pediatric hospitals. A cohort of 49 children, 29 with CKD, including renal transplant (mean age 14.4 ± 2.9 years; range 9-18), and 20 healthy controls (mean age 13.7 ± 3.1 years; range 9-18) had their conventional brain magnet ...[more]

PMID: 29967532

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Project description:BackgroundThe impact of pediatric chronic kidney disease (pCKD) on the brain remains poorly defined. The objective of this study was to compare brain morphometry between children with early-stage pCKD and typically developing peers using structural magnetic resonance imaging (MRI).MethodsThe sample age range was 6-16 years. A total of 18 children with a diagnosis of pCKD (CKD stages 1-3) due to congenital anomalies of the kidney and urinary tract and 24 typically developing peers were included. Volumetric data from MRI and neurocognitive testing were compared using linear models including pCKD status, age, maternal education level, and socioeconomic status.ResultsCerebellar gray matter volume was significantly smaller in pCKD, t(38) = -2.71, p = 0.01. In contrast, cerebral gray matter volume was increased in pCKD, t(38) = 2.08, p = 0.04. Reduced cerebellum gray matter volume was associated with disease severity, operationalized as estimated glomerular filtration rate (eGFR), t(14) = 2.21, p = 0.04 and predicted lower verbal fluency scores in the pCKD sample. Enlarged cerebral gray matter in the pCKD sample predicted lower scores on mathematics assessment.ConclusionsThis study provides preliminary evidence for a morphometric underpinning to the cognitive deficits observed in pCKD.ImpactThe impact of pediatric chronic kidney disease (CKD) on the brain remains poorly defined, with no data linking brain morphometry and observed cognitive deficits noted in this population. We explored the relationship between brain morphometry (using structural magnetic resonance imaging), cognition, and markers of CKD. Cerebellar and cerebral gray matter volumes are different in early CKD. Volumetric decreases in cerebellar gray matter are predicted by lower eGFR, suggesting a link between disease and brain morphometry. Reduced cerebellar gray matter predicted lower verbal fluency for those with pCKD. Enlarged cerebral gray matter in the pCKD sample predicted lower mathematics performance.

Project description:BackgroundFew studies have prospectively evaluated the progression of chronic kidney disease (CKD) in children and adolescents, as well as factors associated with progression.Study designProspective multicenter observational cohort study.Setting & participants496 children and adolescents with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study.PredictorsProteinuria, hypoalbuminemia, blood pressure, dyslipidemia, and anemia.OutcomesParametric failure-time models were used to characterize adjusted associations between baseline levels and changes in predictors and time to a composite event of renal replacement therapy or 50% decline in glomerular filtration rate (GFR).Results398 patients had nonglomerular disease and 98 had glomerular disease; of these, 29% and 41%, respectively, progressed to the composite event after median follow-ups of 5.2 and 3.7 years, respectively. Demographic and clinical characteristics and outcomes differed substantially according to the underlying diagnosis; hence, risk factors for progression were assessed in stratified analyses, and formal interactions by diagnosis were performed. Among patients with nonglomerular disease and after adjusting for baseline GFR, times to the composite event were significantly shorter with urinary protein-creatinine ratio > 2mg/mg, hypoalbuminemia, elevated blood pressure, dyslipidemia, male sex, and anemia, by 79%, 69%, 38%, 40%, 38%, and 45%, respectively. Among patients with glomerular disease, urinary protein-creatinine ratio >2mg/mg, hypoalbuminemia, and elevated blood pressure were associated with significantly reduced times to the composite event by 94%, 71%, and 67%, respectively. Variables expressing change in patient clinical status over the initial year of the study contributed significantly to the model, which was cross-validated internally.LimitationsSmall number of events in glomerular patients and use of internal cross-validation.ConclusionsCharacterization and modeling of risk factors for CKD progression can be used to predict the extent to which these factors, either alone or in combination, would shorten the time to renal replacement therapy or 50% decline in GFR in children with CKD.

Project description:To characterize the distribution of blood pressure (BP), prevalence, and risk factors for hypertension in pediatric chronic kidney disease, we conducted a cross-sectional analysis of baseline BPs in 432 children (mean age 11 years; 60% male; mean glomerular filtration rate 44 mL/min per 1.73 m(2)) enrolled in the Chronic Kidney Disease in Children cohort study. BPs were obtained using an aneroid sphygmomanometer. Glomerular filtration rate was measured by iohexol disappearance. Elevated BP was defined as BP >or=90th percentile for age, gender, and height. Hypertension was defined as BP >or=95th percentile or as self-reported hypertension plus current treatment with antihypertensive medications. For systolic BP, 14% were hypertensive and 11% were prehypertensive (BP 90th to 95th percentile); 68% of subjects with elevated systolic BP were taking antihypertensive medications. For diastolic BP, 14% were hypertensive and 9% were prehypertensive; 53% of subjects with elevated diastolic BP were taking antihypertensive medications. Fifty-four percent of subjects had either systolic or diastolic BP >or=95th percentile or a history of hypertension plus current antihypertensive use. Characteristics associated with elevated BP included black race, shorter duration of chronic kidney disease, absence of antihypertensive medication use, and elevated serum potassium. Among subjects receiving antihypertensive treatment, uncontrolled BP was associated with male sex, shorter chronic kidney disease duration, and absence of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. Thirty-seven percent of children with chronic kidney disease had either elevated systolic or diastolic BP, and 39% of these were not receiving antihypertensives, indicating that hypertension in pediatric chronic kidney disease may be frequently under- or even untreated. Treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may improve BP control in these patients.

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Brain abnormalities in children and adolescents with chronic kidney disease.

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Brain abnormalities in children and adolescents with chronic kidney disease.

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