Nested case-control study reveals increased levels of urinary proteins from human kidney toxicity panels in women predicted to develop preeclampsia.

Abstract

The aim of this study was to evaluate the usefulness of urine concentrations of 12 proteins as a risk parameter for developing preeclampsia (PE). A nested case-control study was designed to determine protein concentrations in urine from women predicted to develop PE (WPD-PE) and normotensive pregnancies (controls). Protein profiles were determined at 12, 16 and 20 gestational weeks (GW) using the Bio-Plex Pro human kidney toxicity Panel 1 and Panel 2 (Bio-Rad). Receiver operating characteristic (ROC) curve analyses were performed. Correlations between proteins and clinical parameters at the time of PE diagnosis were also assessed. Significant differences were observed in urine cystatin C (Cys C) levels at 16 and 20GW and clusterin at 20GW between WPD-PE and controls (P<0.05). ROC analysis revealed that Cys C at 16GW had the highest area under the ROC curve (0.758). At 16GW, patients with urine Cys C levels above 73.7ng/mL had eightfold increased odds for developing PE (odds ratio 7.92; 95% CI 1.3-47.5; P=0.027). A positive correlation was found between urinary Cys C (at 16 and 20GW) and leukocyte counts, total proteins, aspartate aminotransferase, alanine aminotransferase, bilirubin and lactate dehydrogenase at the time of PE diagnosis (P value<0.05). Urinary Cys C and clusterin showed predictive value for PE development in our cohort. Further studies are needed to validate their use as predictive biomarkers for PE and/or their participation in PE pathogenesis.