Diagnostic Indicators of Superimposed Preeclampsia in Women With CKD

Kate Wiles; Kate Bramham; Paul T. Seed; Lesia O. Kurlak; Catherine Nelson-piercy; Hiten D. Mistry; Liz Lightstone; Lucy C. Chappell

doi:10.1016/j.ekir.2019.03.012

Diagnostic Indicators of Superimposed Preeclampsia in Women With CKD

Kate Wiles, Kate Bramham, Paul T. Seed, Lesia O. Kurlak, Catherine Nelson-piercy, Hiten D. Mistry, Liz Lightstone, Lucy C. Chappell

Women & Children's Health

Research output: Contribution to journal › Article › peer-review

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Abstract

IntroductionDiagnosis 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.MethodsPlasma 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.ResultsPlasma concentrations of hyaluronan (67.5 ng/ml vs. 27.5 ng/ml, P = 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.ConclusionThis study suggests that endothelial dysfunction contributes to the pathophysiology of superimposed preeclampsia and a diagnostic role for plasma hyaluronan and VCAM is hypothesized.

Original language	English
Pages (from-to)	842-853
Number of pages	12
Journal	Kidney International Reports
Volume	4
Issue number	6
Early online date	26 Mar 2019
DOIs	https://doi.org/10.1016/j.ekir.2019.03.012
Publication status	Published - 1 Jun 2019

Keywords

preeclampsia
pregnancy
renal insufficiency

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{2265eef7825a45abbafbeb622706435e,

title = "Diagnostic Indicators of Superimposed Preeclampsia in Women With CKD",

abstract = "IntroductionDiagnosis 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.MethodsPlasma 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.ResultsPlasma concentrations of hyaluronan (67.5 ng/ml vs. 27.5 ng/ml, P = 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.ConclusionThis study suggests that endothelial dysfunction contributes to the pathophysiology of superimposed preeclampsia and a diagnostic role for plasma hyaluronan and VCAM is hypothesized.",

keywords = "preeclampsia, pregnancy, renal insufficiency",

author = "Kate Wiles and Kate Bramham and Seed, {Paul T.} and Kurlak, {Lesia O.} and Catherine Nelson-piercy and Mistry, {Hiten D.} and Liz Lightstone and Chappell, {Lucy C.}",

year = "2019",

month = jun,

day = "1",

doi = "10.1016/j.ekir.2019.03.012",

language = "English",

volume = "4",

pages = "842--853",

journal = "Kidney International Reports",

issn = "2468-0249",

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T1 - Diagnostic Indicators of Superimposed Preeclampsia in Women With CKD

AU - Wiles, Kate

AU - Bramham, Kate

AU - Seed, Paul T.

AU - Kurlak, Lesia O.

AU - Nelson-piercy, Catherine

AU - Mistry, Hiten D.

AU - Lightstone, Liz

AU - Chappell, Lucy C.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - IntroductionDiagnosis 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.MethodsPlasma 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.ResultsPlasma concentrations of hyaluronan (67.5 ng/ml vs. 27.5 ng/ml, P = 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.ConclusionThis study suggests that endothelial dysfunction contributes to the pathophysiology of superimposed preeclampsia and a diagnostic role for plasma hyaluronan and VCAM is hypothesized.

AB - IntroductionDiagnosis 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.MethodsPlasma 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.ResultsPlasma concentrations of hyaluronan (67.5 ng/ml vs. 27.5 ng/ml, P = 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.ConclusionThis study suggests that endothelial dysfunction contributes to the pathophysiology of superimposed preeclampsia and a diagnostic role for plasma hyaluronan and VCAM is hypothesized.

KW - preeclampsia

KW - pregnancy

KW - renal insufficiency

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U2 - 10.1016/j.ekir.2019.03.012

DO - 10.1016/j.ekir.2019.03.012

M3 - Article

SN - 2468-0249

VL - 4

SP - 842

EP - 853

JO - Kidney International Reports

JF - Kidney International Reports

IS - 6

ER -

Diagnostic Indicators of Superimposed Preeclampsia in Women With CKD

Abstract

Keywords

UN SDGs

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