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Placental and endothelial biomarkers for the prediction of superimposed pre-eclampsia in chronic kidney disease

Research output: Contribution to journalArticlepeer-review

Kate Wiles, Kate Bramham, Paul T. Seed, Anna Brockbank, Catherine Nelson-Piercy, S. Ananth Karumanchi, Liz Lightstone, Lucy C. Chappell

Original languageEnglish
Pages (from-to)58-64
Number of pages7
JournalPregnancy Hypertension
Volume24
DOIs
PublishedJun 2021

Bibliographical note

Funding Information: LCC is supported by a Research Professorship from the National Institute for Health Research, RP-2014-05-019. Funding Information: The authors acknowledge the following for their assistance with data collection and sample processing: Mairi Alexander, Katherine Clark, Cally Gill, Kat Golding, Ruth Leary, Holly Lovell, Mavis Machirori, Ramona Mannino, Charlotte Mungeam, Haley Tarft, Emma Wayman and Hannah Wilson. KW is funded by The National Institute for Health Research (NIHR) Rare Diseases Translational Research Collaboration as well as the Biomedical Research Centre at Guy's and St. Thomas? NHS Foundation Trust and King's College London under the terms of a doctoral research fellowship. LL is supported by The National Institute for Health Research (NIHR) Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London. LCC is supported by a Research Professorship from the National Institute for Health Research, RP-2014-05-019. PTS is partly funded by Tommy's (Registered charity no. 1060508) and by CLAHRC South London (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. KB has received consulting fees and lecture fees from Alexion. SAK reports grants from Siemens, financial interest from Aggamin Pharmaceuticals, outside the submitted work. In addition, SAK is a co-inventor on multiple patents (USPTO #7,740,849, #7,407,658, #7,335,362, #7,344,892) issued and held by Beth Israel Deaconess Medical Center. SAK has previously served as consultant to Roche Diagnostics and Thermofisher Scientific. CNP has received consulting fees from Alliance Pharma and UCB, and lecture fees from Sanofi, Alexion, Falk, Jenssen and UCB. LL has received lecture fees/honoraria from Alexion and Aurinia, consulting fees from Achillion, Astra-Zeneca, Aurinia, GSK, Pfizer and research grant funding from Roche. All other authors report no conflicts of interest. Funding Information: LL is supported by The National Institute for Health Research (NIHR) Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London. Funding Information: SAK reports grants from Siemens, financial interest from Aggamin Pharmaceuticals, outside the submitted work. In addition, SAK is a co-inventor on multiple patents (USPTO #7,740,849, #7,407,658, #7,335,362, #7,344,892) issued and held by Beth Israel Deaconess Medical Center. SAK has previously served as consultant to Roche Diagnostics and Thermofisher Scientific. Funding Information: KW is funded by The National Institute for Health Research (NIHR) Rare Diseases Translational Research Collaboration as well as the Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London under the terms of a doctoral research fellowship. Funding Information: PTS is partly funded by Tommy’s (Registered charity no. 1060508) and by CLAHRC South London (NIHR). Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Objectives: To evaluate PlGF, sFlt-1, and novel endothelial biomarkers hyaluronan and vascular cell adhesion molecule (VCAM), for the prediction of superimposed pre-eclampsia in women with chronic kidney disease (CKD). Study design: Prospective cohort study of pregnant women with CKD in UK. Main outcome measures: Outcomes including superimposed pre-eclampsia were based on predetermined criteria. Test performances of plasma PlGF, serum sFlt-1:PlGF, hyaluronan and VCAM concentrations were evaluated as area under the receiver-operating curve and at established and exploratory threshold concentrations. Results: There were 232 pregnancies in 221 women with CKD. One third (76/232) developed superimposed pre-eclampsia. From 21 to 37 weeks’ gestation, plasma PlGF was decreased among women that developed superimposed preeclampsia. Plasma PlGF levels < 150 pg/ml had the highest sensitivity (79% 95% CI: 58–91%) and negative predictive value (97%, 95% CI: 93–99%) for the prediction of delivery with superimposed pre-eclampsia within 14 days. Predictive performances of hyaluronan and VCAM were lower than for plasma PlGF. Low plasma PlGF, high hyaluronan and high VCAM concentrations had lower predictive performance in women with pre-pregnancy CKD stages 3–5 compared to stages 1–2. sFlt-1:PlGF > 38 did not usefully predict the need to deliver in women with CKD when measured in serum. Conclusions: Increased surveillance for the need for delivery should take place in women with CKD and plasma PlGF below 150 pg/ml after 20 weeks’ gestation, with awareness that predictive value is reduced as excretory kidney function declines. Maternal endothelial dysfunction may alter the PlGF threshold at which superimposed pre-eclampsia manifests in women with CKD.

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