Summary 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.

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Introduction Children with systemic lupus erythematosus (SLE) have an increased prevalence of kidney disease compared to their adult counterparts. Our goal was to identify potential clinical and laboratory predictors of renal disease. Methods We performed a cohort study of incident and prevalent patients with SLE aged ≤ 19 years. Retrospective data from initial presentation until study enrollment was also collected. Laboratory and clinic data were recorded from each clinic visit including disease activity indices, autoantibodies, urinalyses, blood counts, and metabolic profile. Kidney disease was defined as the presence of abnormal renal biopsy or by American College of Rheumatology case definition for lupus nephritis. Logistic regression analyses were used to determine the association between clinical and laboratory data with kidney disease in those who had renal involvement within 30 days of SLE diagnosis. We also performed a time to event analysis to identify antecedents of renal disease. Results 47 children and adolescents with SLE were followed in the cohort, 91% female and 68% Black. All of the males in the cohort developed renal disease, and all within one month of the diagnosis of SLE. In logistic regression, low serum albumin (Odds Ratio: 4.8, 95% CI: 1.9–12.5) and positive dsDNA antibodies (OR: 3.2, 95% CI: 1.7–5.9) were associated with kidney disease. In longitudinal analyses, isolated sterile pyuria (Hazard Ratio (HR): 3, 95% CI: 1.1–6.4) and low serum albumin (HR: 3.4, 95% CI: 1.7–6.9) were predictors of future kidney disease. The presence of antibodies against Ro were protective against renal disease (HR: 0.2, 95% CI: 0.05–0.5). Conclusion We identified variables associated with kidney disease, both at initial diagnosis of SLE and in longitudinal follow-up in a cohort of children with SLE. The recognition of these abnormal laboratory values may help clinicians identify patients at risk for kidney disease before its onset thus preventing long-term complications.

This study supported the presence of executive dysfunction through a parent report, although the level of impairment was mild and its association with disease severity was related to select executive functions. Few difficulties were reported by older adolescents and young adults with CKD. It will be important for developmental-behavioral pediatricians to be cognizant of the level and pattern of executive function capabilities in their patients with CKD, and possible discrepancies with parent reports, so as to facilitate their management and transition planning.

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BackgroundChronic 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/methodsThe 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.DiscussionThe 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.

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Background and Objectives: Hypertension is an established risk factor for subsequent cardiovascular and renal disease in children as well as adults. Sickle Cell Disease (SCD) is a genetic disorder associated with anemia with the major manifestation of vaso-occlusive crises. While this disease entity involves most organ systems causing vascular and pulmonary injury, little is known about blood pressure (BP) levels or prevalence of hypertension in children and adolescents with SCD. Methods: We enrolled 41 children with severe genotypes of SCD (39 with Hb SS disease and 2 with Hb Sβ0 thalassemia). Study participants underwent 24-hour ambulatory blood pressure monitoring (ABPM). Clinical information regarding duration of SCD, SCD-related complications, requirement for chronic blood transfusion and chronic hydroxyurea therapy were obtained. Baseline characteristics obtained on each participant included age, gender, weight, height, body mass index (BMI) percentile, BMI-Z score and clinic BP. Serum creatinine and cystatin C were obtained to assess estimated glomerular filtration rate (eGFR) with age-based formulas. A random urine sample was obtained for standard urinalysis, albumin and creatinine estimation, to calculate urine albumin to creatinine ratio. Results: Based on ABPM study results participants were categorized into three groups as normal ABPM, abnormal ABPM, or hypertension ABPM (ambulatory hypertension, masked hypertension or severe ambulatory hypertension). The term abnormal ABPM designated participants who did not have normal ABPM or hypertension, but had other abnormal parameters on ABPM (presence of pre-hypertension and/or lack of normal nocturnal dipping). SCD children in the three groups were similar with respect to distribution of age, BMI z-scores, renal function, urine albumin excretion, urine osmolality, hemoglobin, history of chronic blood transfusion, and hydroxyurea therapy. Twelve participants (29.3%) met criteria for hypertension based on ABPM. Of the 12 hypertensive participants, three had clinic hypertension with ambulatory hypertension; and nine had masked hypertension detected on ABPM. Youngest child with ABPM confirmed hypertension was six years of age. Another 18 participants (43.9%) had some abnormal ABPM parameters that were largely present in the sleep period of ABPM. Conclusions: Findings from our study indicate that BP abnormalities are not uncommon in SCD children. Overall, the distribution of confirmed hypertension, largely manifested by masked hypertension, is high in pediatric participants with SCD; as young as 6 years of age. The underlying cause for the relatively high prevalence of masked hypertension and abnormal ABPM parameters including absence of nocturnal BP dip in children with SCD is unclear. Based on our findings more attention should be given to monitoring and management of BP in children with SCD. Early identification of hypertension in SCD children can confer benefit because hypertension is an important modifiable risk factor for progression of cardiovascular and renal disease. Acknowledgment: Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Number P20GM109021; National Kidney Foundation Young Investigator Grant and DE-CTR-ACCEL grant number U54-GM104941 (PI: Binder-Macleod). Disclosures No relevant conflicts of interest to declare.