Novel technologies for the detection of podocytes from preeclamptic patients

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SUMMARY/ABSTRACT Preeclampsia is a complication of pregnancy characterized by elevated blood pressure, proteinuria, and endothelial dysfunction involving multiple organ systems. Worldwide, preeclampsia is the largest cause of fetal and maternal morbidity and mortality, and accounts for nearly 16% of maternal deaths in the United States alone each year. Currently, there is no approved diagnostic test to predict which patients will develop preeclampsia. Patients with preeclampsia require hospitalization and continuous monitoring of the mother and fetus, thus, there is an urgent and unmet need for a diagnostic test that can identify those patients at risk for preeclampsia. Preeclampsia is diagnosed when a patient’s blood pressure measures ≥140/90 mm Hg twice ≥4 hours apart and either proteinuria or one of the following conditions is present: thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema or visual disturbances. Significant efforts are underway to detect preeclampsia prior to disease onset. Recently, it was demonstrated that glomerular podocytes are shed into the urine of preeclamptic patients and can be visualized using podocyte-specific antibodies. Moreover, shed podocytes can be detected in the second trimester, prior to preeclampsia diagnosis, with high sensitivity and specificity. Methods to detect podocytes currently rely on overnight culture and sedimentation of cells onto collagen-coated slides or Cytospin, which is prone to high false-positive rates due to contaminating red blood cells (RBCs) or casts. Inconsistencies in the method of podocyte detection and lengthy, overnight incubations susceptible to contamination weaken the utility of podocytes as a diagnostic marker of preeclampsia. To this end, Affinergy is developing a slide platform that can specifically capture and retain the diagnostic podocytes, while moving the obscuring contaminants to a separate region of the slide. Such a technology is amenable to downstream immunocytochemistry, will improve the diagnostic quality of podocyte capture, and lead to significant cost savings by minimizing time and need for expensive equipment. In this Phase I application, we will focus on developing optimal peptide-modified slides for isolating podocyte visceral epithelial cells from urine to improve the diagnostic quality of clinical podocyte slide preparations.