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Author Notes:

E-mail: kenneth_ataga@med.unc.edu

Conceptualization; Supervision: KIA.

Formal analysis: PM JC.

Funding acquisition: KIA DRA DMP.

Investigation: KIA MC LE JS SKJ DMP ALH.

Methodology: KIA VKD JC ALH.

Resources: KIA DMP.

Writing – original draft: KIA.

Writing – review & editing: VKD MC LE JS SKJ PM DMP JC ALH DRA.

We acknowledge the Clinical and Translational Research Center at the University of North Carolina at Chapel Hill, which is funded by NIH grant UL1RR025747.

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

This work was supported by National Heart, Lung and Blood Institute grants R01HL111659 (KIA, JC, DRA, ALH), U01HL117659 (KIA, JC) and U01HL117684 (DMP), and by an award from the North Carolina State Sickle Cell Program.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • NITRIC-OXIDE BIOAVAILABILITY
  • PULMONARY-HYPERTENSION
  • MEDIATED VASODILATION
  • DIABETIC-NEPHROPATHY
  • KIDNEY-DISEASE
  • GROWTH-FACTOR
  • VEGF-A
  • HYDROXYUREA
  • EXPRESSION
  • VASCULOPATHY
  • Urine
  • Hemoglobin
  • Tyrosine kinases
  • Bilirubin
  • Growth factors
  • Blood plasma
  • Arteries
  • Pathogenesis
  • Nephrology

Albuminuria Is Associated with Endothelial Dysfunction and Elevated Plasma Endothelin-1 in Sickle Cell Anemia

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Journal Title:

PLoS ONE

Volume:

Volume 11, Number 9

Publisher:

, Pages e0162652-e0162652

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2016 Ataga et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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