Diagnostic Indicators of Superimposed Preeclampsia in Women With CKD

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

Abstract

© 2019 International Society of Nephrology 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 = 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.

Citation

Wiles, K., Bramham, K., Seed, P. T., Kurlak, L. O., Mistry, H. D., Nelson-Piercy, C., …Chappell, L. C. (2019). Diagnostic Indicators of Superimposed Preeclampsia in Women With CKD. Kidney International Reports, 4(6), 842-853. https://doi.org/10.1016/j.ekir.2019.03.012

• Journal Article Type: Article
• Acceptance Date: Mar 11, 2019
• Online Publication Date: Mar 26, 2019
• Publication Date: 2019-06
• Deposit Date: Jul 31, 2019
• Publicly Available Date: Jul 31, 2019
• Journal: Kidney International Reports
• Print ISSN: 2468-0249
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 6
• Pages: 842-853
• DOI: https://doi.org/10.1016/j.ekir.2019.03.012
• Keywords: Nephrology
• Public URL: https://nottingham-repository.worktribe.com/output/2362840
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2468024919301172
• Additional Information: This article is maintained by: Elsevier; Article Title: Diagnostic Indicators of Superimposed Preeclampsia in Women With CKD; Journal Title: Kidney International Reports; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ekir.2019.03.012; Content Type: article; Copyright: © 2019 International Society of Nephrology. Published by Elsevier Inc.