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Change in Dyslipidemia with Declining Glomerular Filtration Rate and Increasing Proteinuria in Children with CKD.

ABSTRACT: BACKGROUND AND OBJECTIVES:Dyslipidemia, a risk factor for cardiovascular disease, is common in CKD but its change over time and how that change is influenced by concurrent progression of CKD have not been previously described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:In the CKD in Children study we prospectively followed children with progressive CKD and utilized multivariable, linear mixed-effects models to quantify the longitudinal relationship between within-subject changes in lipid measures (HDL cholesterol, non-HDL cholesterol, triglycerides) and within-subject changes in GFR, proteinuria, and body mass index (BMI). RESULTS:A total of 508 children (76% nonglomerular CKD, 24% glomerular CKD) had 2-6 lipid measurements each, with a median follow-up time of 4 (interquartile range [IQR], 2.1-6.0) years. Among children with nonglomerular CKD, dyslipidemia was common at baseline (35%) and increased significantly as children aged; 43% of children with glomerular CKD had dyslipidemia at baseline and demonstrated persistent levels as they aged. Longitudinal increases in proteinuria were independently associated with significant concomitant increases in non-HDL cholesterol (nonglomerular: 4.9 [IQR, 3.4-6.4] mg/dl; glomerular: 8.5 [IQR, 6.0-11.1] mg/dl) and triglycerides (nonglomerular: 3% [IQR, 0.8%-6%]; glomerular: 5% [IQR, 0.6%-9%]). Decreases in GFR over follow-up were significantly associated with concomitant decreases of HDL cholesterol in children with nonglomerular CKD (-1.2 mg/dl; IQR, -2.1 to -0.4 mg/dl) and increases of non-HDL cholesterol in children with glomerular CKD (3.9 mg/dl; IQR, 1.4-6.5 mg/dl). The effects of increased BMI also affected multiple lipid changes over time. Collectively, glomerular CKD displayed stronger, deleterious associations between within-subject change in non-HDL cholesterol (9 mg/dl versus 1.2 mg/dl; P<0.001) and triglycerides (14% versus 3%; P=0.004), and within-subject change in BMI; similar but quantitatively smaller differences between the two types of CKD were noted for associations of within-subject change in lipids to within-subject change in GFR and proteinuria. CONCLUSIONS:Dyslipidemia is a common and persistent complication in children with CKD and it worsens in proportion to declining GFR, worsening proteinuria, and increasing BMI.

SUBMITTER: Saland JM

PROVIDER: S-EPMC6895497 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Change in Dyslipidemia with Declining Glomerular Filtration Rate and Increasing Proteinuria in Children with CKD.

Saland Jeffrey M JM Kupferman Juan C JC Pierce Christopher B CB Flynn Joseph T JT Mitsnefes Mark M MM Warady Bradley A BA Furth Susan L SL

Clinical journal of the American Society of Nephrology : CJASN 20191111 12

<h4>Background and objectives</h4>Dyslipidemia, a risk factor for cardiovascular disease, is common in CKD but its change over time and how that change is influenced by concurrent progression of CKD have not been previously described.<h4>Design, setting, participants, & measurements</h4>In the CKD in Children study we prospectively followed children with progressive CKD and utilized multivariable, linear mixed-effects models to quantify the longitudinal relationship between within-subject change ...[more]

PMID: 31712386

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Project description:Background and objectivesExposure to particulate matter (PM) <2.5 μm in aerodynamic diameter (PM2.5) has been linked to detrimental health effects. This study aimed to describe the relationship between long-term PM2.5 exposure and kidney disease, including eGFR, level of albuminuria, and incident CKD.Design, setting, participants, & measurementsThe study included 10,997 participants from the Atherosclerosis Risk in Communities cohort who were followed from 1996-1998 through 2016. Monthly mean PM2.5 concentrations (μg/m3) were estimated at geocoded participant addresses using geographic information system-based, spatiotemporal generalized additive mixed models-including geospatial covariates such as land use-and then averaged over the 12-month period preceding participant examination. Covariate-adjusted, cross-sectional associations of PM2.5, baseline eGFR, and urinary albumin-creatinine ratio (UACR) were estimated using linear regression. PM2.5 and incident CKD (defined as follow-up eGFR <60 ml/min per 1.73 m2 with ≥25% eGFR decline relative to baseline, CKD-related hospitalization or death based on International Classification of Diseases 9/10 codes, or development of ESKD) associations were estimated using Cox proportional hazards regression. Modeling was stratified by study site, and stratum-specific estimates were combined using random-effects meta-analyses.ResultsBaseline mean participant age was 63 (±6) years and eGFR was 86 (±16) ml/min per 1.73 m2. There was no significant PM2.5-eGFR association at baseline. Each 1-μg/m3 higher annual average PM2.5 was associated with higher UACR after adjusting for demographics, socioeconomic status, and clinical covariates (percentage difference, 6.6%; 95% confidence interval [95% CI], 2.6% to 10.7%). Each 1-μg/m3 higher annual average PM2.5 was associated with a significantly higher risk of incident CKD (hazard ratio, 1.05; 95% CI, 1.01 to 1.10).ConclusionsExposure to higher annual average PM2.5 concentrations was associated with a higher level of albuminuria and higher risk for incident CKD in a community-based cohort.

Project description:BackgroundEstimating kidney glomerular filtration rate (GFR) is of utmost importance in many clinical conditions. However, very few studies have evaluated the performance of GFR estimating equations over all ages and degrees of kidney impairment. We evaluated the reliability of two major equations for GFR estimation, the CKD-EPI and Schwartz equations, with urinary clearance of inulin as gold standard.Methods and findingsThe study included 10,610 participants referred to the Renal and Metabolic Function Exploration Unit of Edouard Herriot Hospital (Lyon, France). GFR was measured by urinary inulin clearance (only first measurement kept for analysis) then estimated with isotope dilution mass spectrometry (IDMS)-traceable CKD-EPI and Schwartz equations. The participants' ages ranged from 3 to 90 y, and the measured GFRs from 3 to 160 ml/min/1.73 m2. A linear mixed-effects model was used to model the bias (mean ratio of estimated GFR to measured GFR). Equation reliability was also assessed using precision (interquartile range [IQR] of the ratio) and accuracy (percentage of estimated GFRs within the 10% [P10] and 30% [P30] limits above and below the measured GFR). In the whole sample, the mean ratio with the CKD-EPI equation was significantly higher than that with the Schwartz equation (1.17 [95% CI 1.16; 1.18] versus 1.08 [95% CI 1.07; 1.09], p < 0.001, t-test). At GFR values of 60-89 ml/min/1.73 m2, the mean ratios with the Schwartz equation were closer to 1 than the mean ratios with the CKD-EPI equation whatever the age class (1.02 [95% CI 1.01; 1.03] versus 1.15 [95% CI 1.13; 1.16], p < 0.001, t-test). In young adults (18-40 y), the Schwartz equation had a better precision and was also more accurate than the CKD-EPI equation at GFR values under 60 ml/min/1.73 m2 (IQR: 0.32 [95% CI 0.28; 0.33] versus 0.40 [95% CI 0.36; 0.44]; P30: 81.4 [95% CI 78.1; 84.7] versus 63.8 [95% CI 59.7; 68.0]) and also at GFR values of 60-89 ml/min/1.73 m2. In all patients aged ≥65 y, the CKD-EPI equation performed better than the Schwartz equation (IQR: 0.33 [95% CI 0.31; 0.34] versus 0.40 [95% CI 0.38; 0.41]; P30: 77.6 [95% CI 75.7; 79.5] versus 67.5 [95% CI 65.4; 69.7], respectively). In children and adolescents (2-17 y), the Schwartz equation was superior to the CKD-EPI equation (IQR: 0.23 [95% CI 0.21; 0.24] versus 0.33 [95% CI 0.31; 0.34]; P30: 88.6 [95% CI 86.7; 90.4] versus 29.4 [95% CI 26.8; 32.0]). This study is limited by its retrospective design, single-center setting with few non-white patients, and small number of patients with severe chronic kidney disease.ConclusionsThe results from this study suggest that the Schwartz equation may be more reliable than the CKD-EPI equation for estimating GFR in children and adolescents and in adults with mild to moderate kidney impairment up to age 40 y.

Dataset Information

Change in Dyslipidemia with Declining Glomerular Filtration Rate and Increasing Proteinuria in Children with CKD.

Publications

Change in Dyslipidemia with Declining Glomerular Filtration Rate and Increasing Proteinuria in Children with CKD.

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