POCT Detection of Urinary Misfolded Proteins Provides Sensitive and Specific Diagnosis of Preeclampsia

Background: Aggregates of misfolded proteins, which previously were shown to be related to preeclampsia, may be used as diagnostic marker by testing patients' urine. We developed an easy-to-perform POCT (point of care test) method for detecting urinary misfolded proteins we termed Protein Test, and validated its diagnostic utility in a large clinically relevant cohort. Methods: 1,539 women hospitalized at Shengjing Hospital were eligible for the study. Urine samples were tested by Misfolded Protein Test. Consistency analysis were conducted using The American College of Obstetricians and Gynecologists (ACOG, 2013) guidelines as golden standard. Findings: Participants were randomized into training (773) and validation set (766). According to the criterion that identified in the training set, our POCT test was demonstrated in validation set having sensitivity 86.11%, specificity 96.52%, positive predictive value (PPV) 88.57%, and negative predictive value (NPV) 95.69% for diagnosis of early onset preeclampsia, and corresponding value of 75.76%, 96.89%, 69.44%, and 97.22% for all preeclampsia. In addition, patients with preeclampsia history, in-vitro fertilization (IVF), or multifetal pregnancy were demonstrated more susceptible to preeclampsia (all P values below 0.001). Primary hypertension or nephrosis (P < 0.001) were also risk factors to preeclampsia. Interpretation: Our simple and non-invasive Misfolded Protein Test for detecting misfolded proteins is highly sensitive and specific for diagnosis of preeclampsia, especially for early-onset preeclampsia. Furthermore, we confirmed in a large non-selective in-patient population that factors including preeclampsia history, abortion history, IVF, multifetal pregnancy, primary hypertension or nephrosis are each independently significant risk factors of preeclampsia. Clinical Trial Number: registered at chictr.org, number ChiCTR1800017692. Funding Statement: The authors state: study received no external funding. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This research was approved by Medical Ethics Committee of Shengjing Hospital. Written informed consent was waived due to the usage of remaining samples of Urine Routine test.