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

Int Urol Nephrol. 2016 Dec;48(12):2051-2059. doi: 10.1007/s11255-016-1397-6. Epub 2016 Aug 29.


Purpose: The aim of this study was to evaluate the usefulness of urine concentrations of 12 proteins as a risk parameter for developing preeclampsia (PE).

Methods: 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.

Results: Significant differences were observed in urine cystatin C (Cys C) levels at 16 and 20 GW and clusterin at 20 GW between WPD-PE and controls (P < 0.05). ROC analysis revealed that Cys C at 16 GW had the highest area under the ROC curve (0.758). At 16 GW, patients with urine Cys C levels above 73.7 ng/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 20 GW) and leukocyte counts, total proteins, aspartate aminotransferase, alanine aminotransferase, bilirubin and lactate dehydrogenase at the time of PE diagnosis (P value < 0.05).

Conclusions: 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.

Keywords: Biomarkers; Clusterin; Cystatin C; Preeclampsia; Urine.

MeSH terms

  • Adult
  • Biomarkers / urine
  • Case-Control Studies
  • Clusterin / urine*
  • Cystatin C / urine*
  • Female
  • Gestational Age
  • Humans
  • Mexico / epidemiology
  • Pre-Eclampsia* / diagnosis
  • Pre-Eclampsia* / epidemiology
  • Pre-Eclampsia* / urine
  • Predictive Value of Tests
  • Pregnancy
  • Prognosis
  • ROC Curve
  • Risk Assessment
  • Urinalysis / methods


  • Biomarkers
  • Clusterin
  • Cystatin C