title: KRYPTOR-automated angiogenic factor assays and risk of preeclampsia-related adverse outcomes.
abstract: OBJECTIVE
  To evaluate KRYPTOR assays for circulating soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) in risk assessment of adverse outcomes in women with suspected preeclampsia.
  
  
  METHODS
  We studied 412 women carrying a singleton pregnancy from a previous study cohort who were evaluated for suspected preeclampsia. Another 434 nonpreeclamptic patients with plasma samples drawn throughout pregnancy were used to derive normative data. Plasma sFlt1 and PlGF levels were measured on the automated KRYPTOR platform and evaluated for prediction of adverse maternal and perinatal outcomes within 2 weeks. Normative values were used to create a ratio of markers and these values were reported as multiples of median (MoM) for women with and without adverse outcomes. The KRYPTOR assay results were also compared with previously reported measurements obtained using the automated Elecsys platform.
  
  
  RESULTS
  Among participants presenting at <34 weeks (N = 110), patients with subsequent adverse outcome had higher sFlt1, lower PlGF, and higher sFlt1/PlGF ratio compared with women without adverse outcomes: the median (25th, 75th centile) sFlt1 (pg/ml), 9030 (3197, 12,140) versus 1976 (1248, 2937); PlGF (pg/ml), 36 (16, 111) versus 318 (108, 629); and ratio, 285.6 (32.2, 758.5) versus 6.1 (2.3, 20.3) (all p < 0.0001). Higher sFlt1/PlGF ratio correlated negatively with timing of delivery (r = -0.60, p < 0.001) and the risk of adverse outcomes was markedly elevated among women in highest tertile compared with lower tertile (odds ratio, 14.77; 95% confidence interval (CI), 4.28-51.00). The addition of sFlt1/PlGF ratio (≥85) to hypertension and proteinuria significantly improved the prediction for subsequent adverse outcomes (AUC 0.89 (95% CI): 0.82, 0.95) for hypertension, proteinuria, and sFlt1/PlGF (AUC = 0.75 (0.65, 0.85)) for hypertension alone (p = 0.002). Compared with normative controls, women who were evaluated for preeclampsia without adverse outcomes had higher MoM for sFlt1/PlGF ratio; these values were further elevated in women with adverse outcomes. sFlt1/PlGF ratios measured on the KRYPTOR platform were highly correlated with measurements obtained using Elecys platform (r = 0.97, p < 0.001).
  
  
  CONCLUSIONS
  In women with suspected preeclampsia presenting prior to 34 weeks of gestation, KRYPTOR assays for circulating sFlt1 and PlGF when used in conjunction with standard clinical evaluation performs well in the prediction of adverse maternal and perinatal outcomes occurring within 2 weeks of presentation.
authors.affiliation: a Division of Maternal Fetal Medicine/Department of Obstetrics and Gynecology , Beth Israel Deaconess Medical Center , Boston , MA , USA.|b Harvard Medical School , Boston , MA , USA.
authors.forename: Saira
authors.initials: S
authors.lastname: Salahuddin
authors.affiliation: b Harvard Medical School , Boston , MA , USA.|c Division of Nephrology/Department of Medicine , Massachusetts General Hospital , Boston , MA , USA.
authors.forename: Julia B
authors.initials: JB
authors.lastname: Wenger
authors.affiliation: b Harvard Medical School , Boston , MA , USA.|d Center for Vascular Biology and Nephrology Division , Beth Israel Deaconess Medical Center Boston , Boston , MA , USA.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: b Harvard Medical School , Boston , MA , USA.|c Division of Nephrology/Department of Medicine , Massachusetts General Hospital , Boston , MA , USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.affiliation: a Division of Maternal Fetal Medicine/Department of Obstetrics and Gynecology , Beth Israel Deaconess Medical Center , Boston , MA , USA.|b Harvard Medical School , Boston , MA , USA.|d Center for Vascular Biology and Nephrology Division , Beth Israel Deaconess Medical Center Boston , Boston , MA , USA.
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.affiliation: a Division of Maternal Fetal Medicine/Department of Obstetrics and Gynecology , Beth Israel Deaconess Medical Center , Boston , MA , USA.|b Harvard Medical School , Boston , MA , USA.|e Division of Maternal-Fetal Medicine/Department of Obstetrics and Gynecology , University of Chicago , Chicago , IL , USA.
authors.forename: Sarosh
authors.initials: S
authors.lastname: Rana
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor / Q000097:blood*; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011247:Pregnancy; D011256:Pregnancy Outcome; D012307:Risk Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Adverse maternal and perinatal outcomes; KRYPTOR assay; angiogenic factors; hypertension; proteinuria; suspected preeclampsia; triage