Clinical usefulness of angiogenic factors in women with chronic kidney disease and suspected superimposed preeclampsia.

Abstract

Preeclampsia is a condition often superimposed to CKD. The purpose of this study was to evaluate the clinical characteristics and outcomes of pregnant women with chronic kidney disease (CKD) with suspected superimposed preeclampsia, stratified according to the degree of their angiogenic imbalance, as assessed by the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio. Using a cross-sectional design, we studied 171 pregnancies in patients with CKD andwith suspected superimposed preeclampsia, admitted to a teaching hospital. Patients were divided into three groups based on their degree of angiogenic imbalance, evaluated by the sFlt-1/PlGF ratio: no angiogenic imbalance (sFlt-1/PlGF ratio≤ 38), mild angiogenic imbalance (sFlt-1/PlGF ratio> 38 to < 85), and severe angiogenic imbalance (sFlt-1/PlGF ratio≥ 85). Superimposed preeclampsia and preeclampsia-related adverse outcomes were defined according to The American College of Obstetricians and Gynecology criteria.Measurements of sFlt-1 and PlGF were performed on single serum samples using the Elecsys sFlt-1 and PlGF assays (Roche Diagnostics). Serum soluble endoglin (sEng) levels were alsodetermined(ELISA R&D Systems, Minneapolis, MN). Glomerular filtration rate (GFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, whenever possible on pre-prengancy data. Patients with severe angiogenic imbalance had higher rates of confirmed superimposed preeclampsia and preeclampsia-related adverse maternal and perinatal outcomes (p < 0.001) when compared to patients with no or mild angiogenic imbalance. A significant trend towards higher serum sEng levels was observed as the degree of angiogenic imbalance increased. Interestingly, the rate of progression to superimposed preeclampsia increased progressively as the degree of angiogenic imbalance increased (no 11.8%, mild 60.0%, and severe 100%). In women with CKD and suspected superimposed preeclampsia, severe angiogenic imbalance was associated with confirmed superimposed preeclampsia or progression to superimposed preeclampsia. Patients with no angiogenic imbalance displayed lower rates of progression to superimposed preeclampsia, whereas outcomes were intermediate, supporting a systematic use ofsFlt-1/PlGF ratio, and other biomarkers in the clinical management of CKD pregnacies.