Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and commonly by the ap- pearance of urinary protein. This disorder occurs in ~5% of pregnancies worldwide and is the second leading cause of maternal/fetal morbidity and mortality worldwide. In low resource settings, PE accounts for up to 16% of maternal deaths. The etiology of this disease is poorly understood. This confounds therapeutic intervention and makes delivery the only recourse for saving the mother and child. Prognostic and diagnostic tests are highly desirable given the importance of this disease. The most widely used diagnostic criterion is proteinuria ? 300 mg/24 hours, which is based on either measured protein in a 24h-urine collection or predicted from the protein-creatinine ratio in a random urine sample. This measurement commonly requires hospitalization over- night and has a relatively low predictive value. The shortcomings of proteinuria and other clinical measurements with respect to rapid diagnosis have catalyzed the search for alternative, more sensitive bi- omarkers of PE. The fact that serum proteins such as albumin appear in the urine of PE patients suggests that the barrier filtration function of the kidneys is affected by the disease. Our team (Garovic) has a long-standing research interest in understanding the role of renal injury in the pathogenesis and progression of PE. The Ga- rovic lab discovered that specialized kidney epithelial cells, podocytes, were present in urine of PE patients. Our team recently demonstrated the presence of podocoyte-specific extracellular vesicles (EVs) in urine of PE patients. The numbers of EVs and the levels of expression of EV surface markers, podocin and nephrin, corre- lated with the diagnosis of PE. The objective of our team at Sersense is to translate exciting research findings from Mayo Clinic into a simple and robust lateral flow assay (LFA) that will quantify podocyte-derived EVs and the ratio of podocin- and nephrin-expressing EVs for use as diagnostic markers of PE.
Preeclampsia is one of the most common causes of pregnancy complications in the United States and worldwide. The objective of this STTR grant application is to leverage research findings from Mayo Clinic to develop a simple point-of-care test for early and sensitive diagnosis of preeclampsia.