Hepcidin and arterial stiffness in children with systemic lupus erythematosus and lupus nephritis: A cross-sectional study

Research output: Contribution to journalArticle

Abstract

Background Cardiovascular disease is common in patients with systemic lupus erythematosis (SLE) and lupus nephritis (LN). Up to 80% of children with SLE develop kidney disease, which is also associated with increased risk for cardiovascular disease and death compared to those without renal involvement. Hepcidin is an iron-regulatory protein which may contribute to atherosclerosis and is elevated in autoimmune disease. Pulse wave velocity (PWV) is a validated indicator of arterial stiffness, an early marker of cardiovascular risk, and is increased in children with SLE versus healthy controls. Our objective was to quantify hepcidin and PWV in children with SLE and investigate if those with biopsy-proven LN have higher hepcidin levels and higher PWV compared to those without kidney disease. Methods Cross-sectional analysis with hepcidin was measured via ELISA assay in 16 children aged 10–21 years with SLE recruited from a single center. Subjects were classified as having LN if histologic evidence of the disease was documented on a clinical renal biopsy. Serum hepcidin was quantified using a validated competitive enzyme-linked immunoassay. Carotid-femoral PWV was measured using applanation tonometry. Wilcoxon rank sum testing was used to compare median levels of hepcidin, PWV, and other continuous variables by nephritis status. Results The cohort (n = 16) was 93.8% female and 68.8% African-American with mean (SD) 16 (3.6) years. 37.5% (n = 6) had LN. Overall median (IQR) hepcidin was 34.4 (18.9, 91.9) ng/ ml, and PWV 4.4 (4, 4.6) meters/second. Although significance was limited by small sample size, both hepcidin and PWV were higher in the subjects with LN. Median (IQR) hepcidin in subjects with LN was 71.5 (26.4, 116.4) ng/ml compared to 27.9 (18.7, 59.7) ng/ml in those with SLE(p = 0.19). Similarly, median (IQR) PWV in those with LN was 4.4 (4.4, 4.9) meters/ second compared to 3 (3.75, 4.55) meters/second in those with without kidney involvement (p = 0.10). Conclusion PWV and serum hepcidin were higher in subjects with LN compared to those with SLE alone, suggesting that elevated hepcidin levels may be associated with morbid CV changes in children with LN. This association, along with identification of additional predictors of arterial stiffness in patients with LN, warrants further investigation.

Original languageEnglish (US)
Article numbere0214248
JournalPloS one
Volume14
Issue number3
DOIs
StatePublished - Mar 1 2019

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Hepcidins
lupus erythematosus
nephritis
Vascular Stiffness
Lupus Nephritis
Pulse Wave Analysis
cross-sectional studies
Systemic Lupus Erythematosus
Cross-Sectional Studies
Stiffness
Biopsy
kidneys
Kidney Diseases
kidney diseases
Kidney
cardiovascular diseases
biopsy
hepcidin
Cardiovascular Diseases
Iron-Regulatory Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hepcidin and arterial stiffness in children with systemic lupus erythematosus and lupus nephritis : A cross-sectional study. / Atkinson, Meredith; Joo, Sarah; Sule, Sangeeta.

In: PloS one, Vol. 14, No. 3, e0214248, 01.03.2019.

Research output: Contribution to journalArticle

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abstract = "Background Cardiovascular disease is common in patients with systemic lupus erythematosis (SLE) and lupus nephritis (LN). Up to 80{\%} of children with SLE develop kidney disease, which is also associated with increased risk for cardiovascular disease and death compared to those without renal involvement. Hepcidin is an iron-regulatory protein which may contribute to atherosclerosis and is elevated in autoimmune disease. Pulse wave velocity (PWV) is a validated indicator of arterial stiffness, an early marker of cardiovascular risk, and is increased in children with SLE versus healthy controls. Our objective was to quantify hepcidin and PWV in children with SLE and investigate if those with biopsy-proven LN have higher hepcidin levels and higher PWV compared to those without kidney disease. Methods Cross-sectional analysis with hepcidin was measured via ELISA assay in 16 children aged 10–21 years with SLE recruited from a single center. Subjects were classified as having LN if histologic evidence of the disease was documented on a clinical renal biopsy. Serum hepcidin was quantified using a validated competitive enzyme-linked immunoassay. Carotid-femoral PWV was measured using applanation tonometry. Wilcoxon rank sum testing was used to compare median levels of hepcidin, PWV, and other continuous variables by nephritis status. Results The cohort (n = 16) was 93.8{\%} female and 68.8{\%} African-American with mean (SD) 16 (3.6) years. 37.5{\%} (n = 6) had LN. Overall median (IQR) hepcidin was 34.4 (18.9, 91.9) ng/ ml, and PWV 4.4 (4, 4.6) meters/second. Although significance was limited by small sample size, both hepcidin and PWV were higher in the subjects with LN. Median (IQR) hepcidin in subjects with LN was 71.5 (26.4, 116.4) ng/ml compared to 27.9 (18.7, 59.7) ng/ml in those with SLE(p = 0.19). Similarly, median (IQR) PWV in those with LN was 4.4 (4.4, 4.9) meters/ second compared to 3 (3.75, 4.55) meters/second in those with without kidney involvement (p = 0.10). Conclusion PWV and serum hepcidin were higher in subjects with LN compared to those with SLE alone, suggesting that elevated hepcidin levels may be associated with morbid CV changes in children with LN. This association, along with identification of additional predictors of arterial stiffness in patients with LN, warrants further investigation.",
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T1 - Hepcidin and arterial stiffness in children with systemic lupus erythematosus and lupus nephritis

T2 - A cross-sectional study

AU - Atkinson, Meredith

AU - Joo, Sarah

AU - Sule, Sangeeta

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Background Cardiovascular disease is common in patients with systemic lupus erythematosis (SLE) and lupus nephritis (LN). Up to 80% of children with SLE develop kidney disease, which is also associated with increased risk for cardiovascular disease and death compared to those without renal involvement. Hepcidin is an iron-regulatory protein which may contribute to atherosclerosis and is elevated in autoimmune disease. Pulse wave velocity (PWV) is a validated indicator of arterial stiffness, an early marker of cardiovascular risk, and is increased in children with SLE versus healthy controls. Our objective was to quantify hepcidin and PWV in children with SLE and investigate if those with biopsy-proven LN have higher hepcidin levels and higher PWV compared to those without kidney disease. Methods Cross-sectional analysis with hepcidin was measured via ELISA assay in 16 children aged 10–21 years with SLE recruited from a single center. Subjects were classified as having LN if histologic evidence of the disease was documented on a clinical renal biopsy. Serum hepcidin was quantified using a validated competitive enzyme-linked immunoassay. Carotid-femoral PWV was measured using applanation tonometry. Wilcoxon rank sum testing was used to compare median levels of hepcidin, PWV, and other continuous variables by nephritis status. Results The cohort (n = 16) was 93.8% female and 68.8% African-American with mean (SD) 16 (3.6) years. 37.5% (n = 6) had LN. Overall median (IQR) hepcidin was 34.4 (18.9, 91.9) ng/ ml, and PWV 4.4 (4, 4.6) meters/second. Although significance was limited by small sample size, both hepcidin and PWV were higher in the subjects with LN. Median (IQR) hepcidin in subjects with LN was 71.5 (26.4, 116.4) ng/ml compared to 27.9 (18.7, 59.7) ng/ml in those with SLE(p = 0.19). Similarly, median (IQR) PWV in those with LN was 4.4 (4.4, 4.9) meters/ second compared to 3 (3.75, 4.55) meters/second in those with without kidney involvement (p = 0.10). Conclusion PWV and serum hepcidin were higher in subjects with LN compared to those with SLE alone, suggesting that elevated hepcidin levels may be associated with morbid CV changes in children with LN. This association, along with identification of additional predictors of arterial stiffness in patients with LN, warrants further investigation.

AB - Background Cardiovascular disease is common in patients with systemic lupus erythematosis (SLE) and lupus nephritis (LN). Up to 80% of children with SLE develop kidney disease, which is also associated with increased risk for cardiovascular disease and death compared to those without renal involvement. Hepcidin is an iron-regulatory protein which may contribute to atherosclerosis and is elevated in autoimmune disease. Pulse wave velocity (PWV) is a validated indicator of arterial stiffness, an early marker of cardiovascular risk, and is increased in children with SLE versus healthy controls. Our objective was to quantify hepcidin and PWV in children with SLE and investigate if those with biopsy-proven LN have higher hepcidin levels and higher PWV compared to those without kidney disease. Methods Cross-sectional analysis with hepcidin was measured via ELISA assay in 16 children aged 10–21 years with SLE recruited from a single center. Subjects were classified as having LN if histologic evidence of the disease was documented on a clinical renal biopsy. Serum hepcidin was quantified using a validated competitive enzyme-linked immunoassay. Carotid-femoral PWV was measured using applanation tonometry. Wilcoxon rank sum testing was used to compare median levels of hepcidin, PWV, and other continuous variables by nephritis status. Results The cohort (n = 16) was 93.8% female and 68.8% African-American with mean (SD) 16 (3.6) years. 37.5% (n = 6) had LN. Overall median (IQR) hepcidin was 34.4 (18.9, 91.9) ng/ ml, and PWV 4.4 (4, 4.6) meters/second. Although significance was limited by small sample size, both hepcidin and PWV were higher in the subjects with LN. Median (IQR) hepcidin in subjects with LN was 71.5 (26.4, 116.4) ng/ml compared to 27.9 (18.7, 59.7) ng/ml in those with SLE(p = 0.19). Similarly, median (IQR) PWV in those with LN was 4.4 (4.4, 4.9) meters/ second compared to 3 (3.75, 4.55) meters/second in those with without kidney involvement (p = 0.10). Conclusion PWV and serum hepcidin were higher in subjects with LN compared to those with SLE alone, suggesting that elevated hepcidin levels may be associated with morbid CV changes in children with LN. This association, along with identification of additional predictors of arterial stiffness in patients with LN, warrants further investigation.

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