P 41 Diagnostic biomarkers in women with CKD and superimposed pre-eclampsia

Abstract

Introduction Chronic kidney disease (CKD) affects 3% of pregnant women and is associated with an increased risk of pre-eclampsia. Diagnosis of pre-eclampsia in women with CKD is complicated by pre-existing hypertension, proteinuria, and gestational changes in creatinine. A fall in placental growth factor may be a useful adjunct for the diagnosis of pre-eclampsia in women with CKD. Pathological mechanisms that link CKD and pre-eclampsia include endothelial dysfunction, complement dysregulation, kidney injury, and renin-angiotensin system activation. Objectives To quantify biomarkers of the endothelial glycocalyx, complement activation, kidney injury, and the renin-angiotensin system in women with CKD in pregnancy. 1. To evaluate diagnostic test performance for these biomarkers in pre-eclampsia superimposed on CKD. 2. To correlate discriminatory biomarkers with PlGF centile due to the absence of robust clinical diagnostic criteria for pre-eclampsia superimposed on CKD. Patients and methods A case-control cohort of 15 women with CKD and pre-eclampsia were matched for both gestation and stage of CKD with 45 women without pre-eclampsia. Active renin, angiotensinogen, tetrahydroaldosterone, hyaluronan, C3a, C5a, complement factor H, C5b-9 were quantified by ELISA. Intercellular adhesion molecule (I-CAM), Vascular cell adhesion molecule (V-CAM), P-selectin, E-selectin, kidney-injury-molecule-1 (KIM-1) and lipocalin-2 (NGAL) were quantified by Luminex performance assay. Results were correlated with placental growth factor (PlGF) centiles. Results Plasma hyaluronan, V-CAM and urinary C5b-9:creatinine were significantly higher in women with superimposed pre-eclampsia compared to women with CKD who did not develop pre-eclampsia (Figure 1:). Hyaluronan and V-CAM correlated strongly with PlGF centile (Figure 2). Plasma active renin was significantly lower in pre-eclampsia than controls but diagnostic distinction was lost after adjustment for the presence of chronic hypertension. Other biomarkers were not discriminatory. Conclusion Plasma hyaluronan, V-CAM and urinary C5b-9:creatinine may have potential as diagnostic markers for superimposed pre-eclampsia in women with CKD. A large validation study of these biomarkers is in progress. Download : Download high-res image (171KB) Download : Download full-size image Download : Download high-res image (220KB) Download : Download full-size image