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

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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.

No MeSH data available.


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Scatter Plot and Regression Line Between Spot Urine Albumin-Creatinine Ratio and 24-Hour Urine Protein: Urine albumin-creatinine ratio is strongly correlated with total urinary protein assessed by 24-hour urine collection (ρ = 0.90; 95% confidence interval [CI]: 0.75–0.95, p < 0.0001).
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pone.0162652.g003: Scatter Plot and Regression Line Between Spot Urine Albumin-Creatinine Ratio and 24-Hour Urine Protein: Urine albumin-creatinine ratio is strongly correlated with total urinary protein assessed by 24-hour urine collection (ρ = 0.90; 95% confidence interval [CI]: 0.75–0.95, p < 0.0001).

Mentions: As UACR, assessed by spot urine collections, was the primary variable of interest in this study, we evaluated the correlation between this variable and 24-hour urine protein collection, the gold standard for assessment of proteinuria. UACR was strongly correlated with total urinary protein assessed by 24-hour urine collection (ρ = 0.90; 95% CI: 0.75–0.95, p < 0.0001) (Fig 3). In addition, UACR assessed by spot albumin-creatinine ratio was strongly correlated with urine aliquots for albumin-creatinine ratio obtained from the 24-hour urine collection (ρ = 0.97; 95% CI: 0.92–0.99, p < 0.0001) (Fig 4).


Albuminuria Is Associated with Endothelial Dysfunction and Elevated Plasma Endothelin-1 in Sickle Cell Anemia
Scatter Plot and Regression Line Between Spot Urine Albumin-Creatinine Ratio and 24-Hour Urine Protein: Urine albumin-creatinine ratio is strongly correlated with total urinary protein assessed by 24-hour urine collection (ρ = 0.90; 95% confidence interval [CI]: 0.75–0.95, p < 0.0001).
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5036885&req=5

pone.0162652.g003: Scatter Plot and Regression Line Between Spot Urine Albumin-Creatinine Ratio and 24-Hour Urine Protein: Urine albumin-creatinine ratio is strongly correlated with total urinary protein assessed by 24-hour urine collection (ρ = 0.90; 95% confidence interval [CI]: 0.75–0.95, p < 0.0001).
Mentions: As UACR, assessed by spot urine collections, was the primary variable of interest in this study, we evaluated the correlation between this variable and 24-hour urine protein collection, the gold standard for assessment of proteinuria. UACR was strongly correlated with total urinary protein assessed by 24-hour urine collection (ρ = 0.90; 95% CI: 0.75–0.95, p < 0.0001) (Fig 3). In addition, UACR assessed by spot albumin-creatinine ratio was strongly correlated with urine aliquots for albumin-creatinine ratio obtained from the 24-hour urine collection (ρ = 0.97; 95% CI: 0.92–0.99, p < 0.0001) (Fig 4).

View Article: PubMed Central - PubMed

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 (&rho; = -0.45, p = 0.031). In univariate analysis, UACR was correlated with VEGF (&rho; = -0.49; 95% CI: -0.75 &ndash;-0.1, p = 0.015), plasma hemoglobin (&rho; = 0.50; 95% CI: 0.11&ndash;0.75, p = 0.013) and ET-1 (&rho; = 0.40; 95% CI: -0.03&ndash;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 (&rho; = 0.90, p &lt; 0.0001) and urine aliquots for albumin-creatinine ratio obtained from the 24-hour urine collection (&rho; = 0.97, p &lt; 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.

No MeSH data available.


Related in: MedlinePlus