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

Abstract

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). Prospective cohort study of pregnant women with CKD in UK. 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. There were 232 pregnancies in 221 women with CKD. One third (76/232) developed superimposed pre-eclampsia. From 21 to 37weeks' gestation, plasma PlGF was decreased among women that developed superimposed preeclampsia. Plasma PlGF levels<150pg/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 14days. 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. Increased surveillance for the need for delivery should take place in women with CKD and plasma PlGF below 150pg/ml after 20weeks' 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.