Albuminuria is associated with endothelial dysfunction and elevated plasma endothelin-1 in sickle cell anemia

Kenneth Ataga, Vimal K. Derebail, Melissa Caughey, Laila Elsherif, Jessica H. Shen, Susan K. Jones, Poulami Maitra, David M. Pollock, Jianwen Cai, David R. Archer, Alan L. Hinderliter

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Abstract

Background: The pathogenesis of albuminuria in SCD remains incompletely understood. We evaluated the association of albuminuria with measures of endothelial function, and explored associations of both albuminuria and measures of endothelial function with selected biological variables (vascular endothelial growth factor [VEGF], endothelin-1 [ET-1], soluble fms-like tyrosine kinase-1 [sFLT-1], soluble vascular cell adhesion molecule-1 [soluble VCAM-1] and plasma hemoglobin). Methods: Spot urine measurements for albumin-creatinine ratio (UACR) and 24-hour urine protein were obtained. Endothelial function was assessed using brachial artery ultrasound with measurements of flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NTMD) and hyperemic velocity. Results: Twenty three subjects with varying degrees of albuminuria were evaluated. UACR was significantly correlated with FMD (ρ = -0.45, p = 0.031). In univariate analysis, UACR was correlated with VEGF (ρ = -0.49; 95% CI: -0.75-0.1, p = 0.015), plasma hemoglobin (ρ = 0.50; 95% CI: 0.11-0.75, p = 0.013) and ET-1 (ρ = 0.40; 95% CI: -0.03-0.69, p = 0.06). Multivariable analysis showed significant associations of ET-1 (estimate: 455.1 [SE: 198.3], p = 0.02), VEGF (estimate: -1.1 [SE: 0.53], p = 0.04) and sFLT-1 (estimate: -1.14 [SE: 0.49], p = 0.02) with UACR. Only ET-1 (estimate: -8.03 [SE: 3.87], p = 0.04) was significantly associated with FMD in multivariable analyses. Finally, UACR was correlated with both 24-hour urine protein (ρ = 0.90, p < 0.0001) and urine aliquots for albumin-creatinine ratio obtained from the 24-hour urine collection (ρ = 0.97, p < 0.0001). Conclusion: This study provides more definitive evidence for the association of albuminuria with endothelial dysfunction in SCD. Elevated circulating levels of ET-1 may contribute to SCD-related glomerulopathy by mediating endothelial dysfunction.

Original languageEnglish (US)
Article numbere0162652
JournalPloS one
Volume11
Issue number9
DOIs
StatePublished - Sep 1 2016

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sickle cell anemia
endothelins
Albuminuria
Sickle Cell Anemia
Endothelin-1
Albumins
Creatinine
urine
Urine
creatinine
albumins
Plasmas
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-1
vascular endothelial growth factors
Dilatation
Hemoglobins
tyrosine
hemoglobin
phosphotransferases (kinases)

All Science Journal Classification (ASJC) codes

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

Cite this

Albuminuria is associated with endothelial dysfunction and elevated plasma endothelin-1 in sickle cell anemia. / Ataga, Kenneth; Derebail, Vimal K.; Caughey, Melissa; Elsherif, Laila; Shen, Jessica H.; Jones, Susan K.; Maitra, Poulami; Pollock, David M.; Cai, Jianwen; Archer, David R.; Hinderliter, Alan L.

In: PloS one, Vol. 11, No. 9, e0162652, 01.09.2016.

Research output: Contribution to journalArticle

Ataga, K, Derebail, VK, Caughey, M, Elsherif, L, Shen, JH, Jones, SK, Maitra, P, Pollock, DM, Cai, J, Archer, DR & Hinderliter, AL 2016, 'Albuminuria is associated with endothelial dysfunction and elevated plasma endothelin-1 in sickle cell anemia', PloS one, vol. 11, no. 9, e0162652. https://doi.org/10.1371/journal.pone.0162652
Ataga, Kenneth ; Derebail, Vimal K. ; Caughey, Melissa ; Elsherif, Laila ; Shen, Jessica H. ; Jones, Susan K. ; Maitra, Poulami ; Pollock, David M. ; Cai, Jianwen ; Archer, David R. ; Hinderliter, Alan L. / Albuminuria is associated with endothelial dysfunction and elevated plasma endothelin-1 in sickle cell anemia. In: PloS one. 2016 ; Vol. 11, No. 9.
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abstract = "Background: The pathogenesis of albuminuria in SCD remains incompletely understood. We evaluated the association of albuminuria with measures of endothelial function, and explored associations of both albuminuria and measures of endothelial function with selected biological variables (vascular endothelial growth factor [VEGF], endothelin-1 [ET-1], soluble fms-like tyrosine kinase-1 [sFLT-1], soluble vascular cell adhesion molecule-1 [soluble VCAM-1] and plasma hemoglobin). Methods: Spot urine measurements for albumin-creatinine ratio (UACR) and 24-hour urine protein were obtained. Endothelial function was assessed using brachial artery ultrasound with measurements of flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NTMD) and hyperemic velocity. Results: Twenty three subjects with varying degrees of albuminuria were evaluated. UACR was significantly correlated with FMD (ρ = -0.45, p = 0.031). In univariate analysis, UACR was correlated with VEGF (ρ = -0.49; 95{\%} CI: -0.75-0.1, p = 0.015), plasma hemoglobin (ρ = 0.50; 95{\%} CI: 0.11-0.75, p = 0.013) and ET-1 (ρ = 0.40; 95{\%} CI: -0.03-0.69, p = 0.06). Multivariable analysis showed significant associations of ET-1 (estimate: 455.1 [SE: 198.3], p = 0.02), VEGF (estimate: -1.1 [SE: 0.53], p = 0.04) and sFLT-1 (estimate: -1.14 [SE: 0.49], p = 0.02) with UACR. Only ET-1 (estimate: -8.03 [SE: 3.87], p = 0.04) was significantly associated with FMD in multivariable analyses. Finally, UACR was correlated with both 24-hour urine protein (ρ = 0.90, p < 0.0001) and urine aliquots for albumin-creatinine ratio obtained from the 24-hour urine collection (ρ = 0.97, p < 0.0001). Conclusion: This study provides more definitive evidence for the association of albuminuria with endothelial dysfunction in SCD. Elevated circulating levels of ET-1 may contribute to SCD-related glomerulopathy by mediating endothelial dysfunction.",
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T1 - Albuminuria is associated with endothelial dysfunction and elevated plasma endothelin-1 in sickle cell anemia

AU - Ataga, Kenneth

AU - Derebail, Vimal K.

AU - Caughey, Melissa

AU - Elsherif, Laila

AU - Shen, Jessica H.

AU - Jones, Susan K.

AU - Maitra, Poulami

AU - Pollock, David M.

AU - Cai, Jianwen

AU - Archer, David R.

AU - Hinderliter, Alan L.

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N2 - Background: The pathogenesis of albuminuria in SCD remains incompletely understood. We evaluated the association of albuminuria with measures of endothelial function, and explored associations of both albuminuria and measures of endothelial function with selected biological variables (vascular endothelial growth factor [VEGF], endothelin-1 [ET-1], soluble fms-like tyrosine kinase-1 [sFLT-1], soluble vascular cell adhesion molecule-1 [soluble VCAM-1] and plasma hemoglobin). Methods: Spot urine measurements for albumin-creatinine ratio (UACR) and 24-hour urine protein were obtained. Endothelial function was assessed using brachial artery ultrasound with measurements of flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NTMD) and hyperemic velocity. Results: Twenty three subjects with varying degrees of albuminuria were evaluated. UACR was significantly correlated with FMD (ρ = -0.45, p = 0.031). In univariate analysis, UACR was correlated with VEGF (ρ = -0.49; 95% CI: -0.75-0.1, p = 0.015), plasma hemoglobin (ρ = 0.50; 95% CI: 0.11-0.75, p = 0.013) and ET-1 (ρ = 0.40; 95% CI: -0.03-0.69, p = 0.06). Multivariable analysis showed significant associations of ET-1 (estimate: 455.1 [SE: 198.3], p = 0.02), VEGF (estimate: -1.1 [SE: 0.53], p = 0.04) and sFLT-1 (estimate: -1.14 [SE: 0.49], p = 0.02) with UACR. Only ET-1 (estimate: -8.03 [SE: 3.87], p = 0.04) was significantly associated with FMD in multivariable analyses. Finally, UACR was correlated with both 24-hour urine protein (ρ = 0.90, p < 0.0001) and urine aliquots for albumin-creatinine ratio obtained from the 24-hour urine collection (ρ = 0.97, p < 0.0001). Conclusion: This study provides more definitive evidence for the association of albuminuria with endothelial dysfunction in SCD. Elevated circulating levels of ET-1 may contribute to SCD-related glomerulopathy by mediating endothelial dysfunction.

AB - Background: The pathogenesis of albuminuria in SCD remains incompletely understood. We evaluated the association of albuminuria with measures of endothelial function, and explored associations of both albuminuria and measures of endothelial function with selected biological variables (vascular endothelial growth factor [VEGF], endothelin-1 [ET-1], soluble fms-like tyrosine kinase-1 [sFLT-1], soluble vascular cell adhesion molecule-1 [soluble VCAM-1] and plasma hemoglobin). Methods: Spot urine measurements for albumin-creatinine ratio (UACR) and 24-hour urine protein were obtained. Endothelial function was assessed using brachial artery ultrasound with measurements of flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NTMD) and hyperemic velocity. Results: Twenty three subjects with varying degrees of albuminuria were evaluated. UACR was significantly correlated with FMD (ρ = -0.45, p = 0.031). In univariate analysis, UACR was correlated with VEGF (ρ = -0.49; 95% CI: -0.75-0.1, p = 0.015), plasma hemoglobin (ρ = 0.50; 95% CI: 0.11-0.75, p = 0.013) and ET-1 (ρ = 0.40; 95% CI: -0.03-0.69, p = 0.06). Multivariable analysis showed significant associations of ET-1 (estimate: 455.1 [SE: 198.3], p = 0.02), VEGF (estimate: -1.1 [SE: 0.53], p = 0.04) and sFLT-1 (estimate: -1.14 [SE: 0.49], p = 0.02) with UACR. Only ET-1 (estimate: -8.03 [SE: 3.87], p = 0.04) was significantly associated with FMD in multivariable analyses. Finally, UACR was correlated with both 24-hour urine protein (ρ = 0.90, p < 0.0001) and urine aliquots for albumin-creatinine ratio obtained from the 24-hour urine collection (ρ = 0.97, p < 0.0001). Conclusion: This study provides more definitive evidence for the association of albuminuria with endothelial dysfunction in SCD. Elevated circulating levels of ET-1 may contribute to SCD-related glomerulopathy by mediating endothelial dysfunction.

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