Abstract
A Rolfo, R Attini, AM Nuzzo, et al. Kidney International 2012, published online 26th September 2012 ahead of print; doi: 10.1038/ki.2012.348
The leading cause of fetal–maternal morbidity and mortality is pre-eclampsia (PE), which manifests as proteinuria and hypertension in 5–8% of pregnancies. Distinguishing PE from chronic kidney disease (CKD) is important since earlier delivery is warranted in PE. However, this is complicated by similarities in clinical presentation and the current lack of discriminatory biomarkers. Rolfo et al. investigated whether the maternal serum concentration of two pre-eclamptic markers (placental growth factor [PlGF] and soluble FMS-like tyrosine kinase-1 [sFlt-1]) could be used in the third trimester to differentiate PE from CKD. Pathogenic sFlt-1: PlGF ratio imbalance was hypothesized in PE but not CKD.
Serum concentrations of PlGF and sFlt-1 were measured by electrochemoluminescence immunoassays (Elecsys, Roche Diagnostics, Burgess Hill, West Sussex, RH15 9RY, UK) using a Cobas-e-411 (Roche Diagnostics, Burgess Hill, West Sussex, RH15 9RY, UK) immunoanalyser in venous blood samples collected without anticoagulant or gel from 34 pre-eclamptic patients, 23 women with CKD in pregnancy and 38 healthy controls. sFlt-1: PlGF ratios were calculated.
Significantly higher concentrations of sFlt-1 (5.12-fold, P < 0.0001) and significantly lower concentrations of PlGF (17.4-fold, P < 0.0001) were found in pre-eclamptic women relative to women with CKD. This was replicated when pre-eclamptic women were compared with controls (4.25-fold higher, sFlt-1; 12.5-fold lower, PlGF; P < 0.0001). However, there were no significant differences between either sFlt-1 or PlGF concentrations in CKD and control patients. Cut-off values of 7715 and 88.2 ng/L for sFlt-1 and PlGF, respectively, discriminated PE from CKD with >90% sensitivity and specificity.
The sFlt-1: PlGF ratio was significantly higher in PE than in both controls and women with CKD (25-fold higher, P < 0.0001) whereas significant differences were not observed between controls and CKD patients. A ratio cut-off of 148.75 differentiated PE from CKD with 100% sensitivity and specificity.
sFlt-1 and PlGF concentrations in maternal serum were proposed as the first biomarkers for distinguishing PE from CKD in the third trimester of pregnancy, with the sFlt-1: PlGF ratio having even higher discriminatory power. A larger, prospective, multicentre study is planned to address limitations in sample size but, if verified, this study has the potential to improve management of proteinuria and hypertension in pregnancy.