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

Jeffrey M. Saland, Juan C. Kupferman, Christopher B. Pierce, Joseph T. Flynn, Mark M. Mitsnefes, Bradley A. Warady, Susan L. Furth

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1711-1718
Number of pages8
JournalClinical journal of the American Society of Nephrology : CJASN
Volume14
Issue number12
DOIs
StatePublished - Dec 6 2019

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Dyslipidemias
Glomerular Filtration Rate
Proteinuria
Body Mass Index
Cholesterol
Lipids
Triglycerides
HDL Cholesterol
Cardiovascular Diseases

Keywords

  • body mass
  • cardiovascular disease
  • cardiovascular diseases
  • child
  • cholesterol
  • chronic kidney disease
  • chronic renal insufficiency
  • dyslipidemia
  • dyslipidemias
  • follow-up studies
  • glomerular filtration rate
  • HDL cholesterol
  • HDL lipoproteins
  • humans
  • lipids
  • pediatric nephrology
  • proteinuria
  • risk factors
  • triglycerides

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

Cite this

Change in Dyslipidemia with Declining Glomerular Filtration Rate and Increasing Proteinuria in Children with CKD. / Saland, Jeffrey M.; Kupferman, Juan C.; Pierce, Christopher B.; Flynn, Joseph T.; Mitsnefes, Mark M.; Warady, Bradley A.; Furth, Susan L.

In: Clinical journal of the American Society of Nephrology : CJASN, Vol. 14, No. 12, 06.12.2019, p. 1711-1718.

Research output: Contribution to journalArticle

Saland, Jeffrey M. ; Kupferman, Juan C. ; Pierce, Christopher B. ; Flynn, Joseph T. ; Mitsnefes, Mark M. ; Warady, Bradley A. ; Furth, Susan L. / Change in Dyslipidemia with Declining Glomerular Filtration Rate and Increasing Proteinuria in Children with CKD. In: Clinical journal of the American Society of Nephrology : CJASN. 2019 ; Vol. 14, No. 12. pp. 1711-1718.
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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.",
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author = "Saland, {Jeffrey M.} and Kupferman, {Juan C.} and Pierce, {Christopher B.} and Flynn, {Joseph T.} and Mitsnefes, {Mark M.} and Warady, {Bradley A.} and Furth, {Susan L.}",
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TY - JOUR

T1 - Change in Dyslipidemia with Declining Glomerular Filtration Rate and Increasing Proteinuria in Children with CKD

AU - Saland, Jeffrey M.

AU - Kupferman, Juan C.

AU - Pierce, Christopher B.

AU - Flynn, Joseph T.

AU - Mitsnefes, Mark M.

AU - Warady, Bradley A.

AU - Furth, Susan L.

PY - 2019/12/6

Y1 - 2019/12/6

N2 - 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.

AB - 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.

KW - body mass

KW - cardiovascular disease

KW - cardiovascular diseases

KW - child

KW - cholesterol

KW - chronic kidney disease

KW - chronic renal insufficiency

KW - dyslipidemia

KW - dyslipidemias

KW - follow-up studies

KW - glomerular filtration rate

KW - HDL cholesterol

KW - HDL lipoproteins

KW - humans

KW - lipids

KW - pediatric nephrology

KW - proteinuria

KW - risk factors

KW - triglycerides

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