Diagnostic indicators of superimposed preeclampsia in women with CKD
File(s)
Author(s)
Type
Journal Article
Abstract
Introduction: Diagnosis of superimposed preeclampsia in women with chronic kidney disease (CKD) is
complicated by the presence of hypertension and proteinuria due to renal disease. The aims of this study
were to determine mechanistic links between superimposed preeclampsia and renin-angiotensin system
activation, endothelial pathology, complement dysfunction, and tubular injury, and to explore the role of
diagnostic indicators of superimposed preeclampsia.
Methods: Plasma and urinary biomarkers derived from the renin-angiotensin system (active renin,
angiotensinogen), endothelial glycocalyx (hyaluronan, intercellular adhesion molecule, vascular cell
adhesion molecule [VCAM], P-selectin, E-selectin), complement activation (C3a, C5a, complement factor H,
C5b-9), and tubular injury (kidney injury molecule-1, urinary lipocalin-2) were quantified in 60 pregnant
women with CKD including 15 women at the time of superimposed preeclampsia diagnosis and 45 women
who did not develop superimposed preeclampsia, 18 women with preeclampsia, and 20 normal pregnancies. Correlation with placental growth factor was assessed.
Results: Plasma concentrations of hyaluronan (67.5 ng/ml vs. 27.5 ng/ml, P ¼ 0.0017, receiver operating
characteristic area 0.80) and VCAM (1132 ng/ml vs. 659 ng/ml, P < 0.0001, receiver operating characteristic
area 0.86) distinguished women with CKD and superimposed preeclampsia from those without superimposed preeclampsia, and correlated with placental growth factor concentration. The diagnostic
discrimination of markers of the renin-angiotensin system was reduced by adjustment for chronic hypertension, antihypertensive drug use, and black ethnicity. Other markers offered limited or no diagnostic
discrimination for superimposed preeclampsia.
Conclusion: This study suggests that endothelial dysfunction contributes to the pathophysiology of
superimposed preeclampsia and a diagnostic role for plasma hyaluronan and VCAM is hypothesized.
complicated by the presence of hypertension and proteinuria due to renal disease. The aims of this study
were to determine mechanistic links between superimposed preeclampsia and renin-angiotensin system
activation, endothelial pathology, complement dysfunction, and tubular injury, and to explore the role of
diagnostic indicators of superimposed preeclampsia.
Methods: Plasma and urinary biomarkers derived from the renin-angiotensin system (active renin,
angiotensinogen), endothelial glycocalyx (hyaluronan, intercellular adhesion molecule, vascular cell
adhesion molecule [VCAM], P-selectin, E-selectin), complement activation (C3a, C5a, complement factor H,
C5b-9), and tubular injury (kidney injury molecule-1, urinary lipocalin-2) were quantified in 60 pregnant
women with CKD including 15 women at the time of superimposed preeclampsia diagnosis and 45 women
who did not develop superimposed preeclampsia, 18 women with preeclampsia, and 20 normal pregnancies. Correlation with placental growth factor was assessed.
Results: Plasma concentrations of hyaluronan (67.5 ng/ml vs. 27.5 ng/ml, P ¼ 0.0017, receiver operating
characteristic area 0.80) and VCAM (1132 ng/ml vs. 659 ng/ml, P < 0.0001, receiver operating characteristic
area 0.86) distinguished women with CKD and superimposed preeclampsia from those without superimposed preeclampsia, and correlated with placental growth factor concentration. The diagnostic
discrimination of markers of the renin-angiotensin system was reduced by adjustment for chronic hypertension, antihypertensive drug use, and black ethnicity. Other markers offered limited or no diagnostic
discrimination for superimposed preeclampsia.
Conclusion: This study suggests that endothelial dysfunction contributes to the pathophysiology of
superimposed preeclampsia and a diagnostic role for plasma hyaluronan and VCAM is hypothesized.
Date Issued
2019-06-01
Date Acceptance
2019-03-11
Citation
Kidney International Reports, 2019, 4 (6), pp.842-853
ISSN
2468-0249
Publisher
Elsevier
Start Page
842
End Page
853
Journal / Book Title
Kidney International Reports
Volume
4
Issue
6
Copyright Statement
© 2019 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Identifier
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Subjects
Science & Technology
Life Sciences & Biomedicine
Urology & Nephrology
preeclampsia
pregnancy
renal insufficiency
PLACENTAL GROWTH-FACTOR
ANGIOTENSIN-ALDOSTERONE SYSTEM
URINARY ANGIOTENSINOGEN
HYPERTENSIVE DISORDERS
ENDOTHELIAL GLYCOCALYX
ACTIVATION PRODUCTS
PREGNANCY OUTCOMES
MATERNAL SERUM
COMPLEMENT
BIOMARKERS
Publication Status
Published
Date Publish Online
2019-03-26